View allAll Photos Tagged coronaviruse
Having completed his PhD in Biochemistry, Brian has now begun post-doctoral work on the structure of the spike glycoproteins of coronaviruses - these proteins are needed for viral entry into a host cell, so his research should help with finding effective vaccines. Coronaviruses cause a range of respiratory tract infections ranging from mild to potentially lethal (such as COVID-19), so Brian is taking his work very seriously.
For Macro Mondays theme 'Plastic'. I spotted this strange little pink plastic object at my local charity shop and immediately thought 'virus'. I was very surprised that there were red/green/blue lights inside that came on for several seconds when the 'virus' was jiggled.
No snails were harmed in the making of this photograph.
皆様へ お元気でしょうか？何時も優しいコメント有り難うございます。今日は何とか投稿出来ました。こんな時期なので皆
様にはご無沙汰します。どうかコロナウイルスにはお気を付けください。
To everyone, how are you? Thank you for your kind comments. I managed to post today. It's such a time, so I'm sorry for everyone. Please be careful about coronaviruses.
Have a wonderful day!!
The anthers on ivy flowers looking a bit like the spike glycoprotein of coronaviruses.
Killing Joke - I Am The Virus
Costco traces its history back to 1976, when Sol Price, a pioneer in warehouse club retailing, opened the first Price Club in San Diego. ... Sinegal opened the first Costco in Seattle in 1983. The Price Company (corporate parent of Price Club) and Costco merged in 1993 to become Price/Costco.
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Just like there are different types of related viruses that cause smallpox, chickenpox, and monkeypox, different coronaviruses cause different diseases in people. The Severe Acute Respiratory Syndrome (SARS) coronavirus causes SARS and the Middle East Respiratory Syndrome (MERS) coronavirus causes MERS. The novel coronavirus responsible for the current pandemic, SARS-CoV-2, is one of seven types of known human coronaviruses. SARS-CoV-2, like the MERS and SARS coronaviruses, likely evolved from a virus previously found in animals. The remaining known coronaviruses cause a significant percentage of colds in adults and children, and these are not a serious threat for otherwise healthy adults.
CHE COSA SONO I CORONAVIRUS?
I Coronavirus sono una famiglia di Virus che possono causare diverse infezioni, dal comune raffreddore a malattie come la MERS (Sindrome respiratoria del Medio Oriente) e la SARS (Sindrome Respiratoria Acuta Grave).
CHE COS'E' UN NUOVO CORONAVIRUS?
Un nuovo Coronavirus (nCoV) è un nuovo ceppo di coronavirus che non è stato precedentemente mai identificato nell'uomo.
Il nuovo Coronavirus 2019, denominato SARS-CoV-2, è un virus a RNA rivestito da un capside e da un peri-capside attraversato da strutture glicoproteiche che gli conferiscono il tipico aspetto ‘a corona'. Fa parte della grande famiglia dei coronavirus ed è geneticamente collocato all'interno del genus Betacoronavirus, con un clade distinto nel lineage B del sub-genus Sarbecovirus così come due ceppi Sars-like non umani (pipistrelli).
La diffusione del SARS-CoV-2 potrebbe essere partita dal mercato del pesce di Wuhan, nella provincia cinese di Hubei. Informazione attualmente smentita da un gruppo di scienziati cinesi pubblicata sulla rivista Lancet.
La situazione è in costante evoluzione. L'ECDC pubblica ogni giorno un aggiornamento epidemiologico (www.ecdc.europa.eu/en/geographical-distribution-2019-ncov...)
CORONAVIRUS
Coronaviruses (CoV) are a large family of viruses that cause illness ranging from the common cold to more severe diseases such as Middle East Respiratory Syndrome (MERS-CoV) and Severe Acute Respiratory Syndrome (SARS-CoV). A novel coronavirus (nCoV) is a new strain that has not been previously identified in humans.
Coronaviruses are zoonotic, meaning they are transmitted between animals and people. Detailed investigations found that SARS-CoV was transmitted from civet cats to humans and MERS-CoV from dromedary camels to humans. Several known coronaviruses are circulating in animals that have not yet infected humans.
Common signs of infection include respiratory symptoms, fever, cough, shortness of breath and breathing difficulties. In more severe cases, infection can cause pneumonia, severe acute respiratory syndrome, kidney failure and even death.
Standard recommendations to prevent infection spread include regular hand washing, covering mouth and nose when coughing and sneezing, thoroughly cooking meat and eggs. Avoid close contact with anyone showing symptoms of respiratory illness such as coughing and sneezing.
Man wearing very old gas mask it looks like it was from the war shopping in Brentwood High Street Essex to protect him from COVID-19
New York, New York - March 14, 2020: You can definitely see the impact of the Coronavirus in the streets of New York and especially Chinatown. These photos were taken yesterday on what would normally be a busy time for shopping and entertainment...especially as the weather is starting to warm up. Retail shops were mostly empty except for employees. Chinatown was devoid of any significant activity. Interestingly enough, the local authorities have not reported any cases in this area so it appears the movement and travel restrictions are working.
The homeless are some of the most vulnerable people who may be at risk of becoming seriously ill with coronaviruses. They often have health problems and are therefore not particularly aware of cough or breathing problems.
The US intelligence community has been unable to determine the origins of Covid-19, and is split on whether it leaked from a lab or developed in nature, according to a new report.
The report issued by the office that oversees the nation's 18 spy agencies did conclusively determine that it was not developed as a biological weapon.
Experts warn that time is running out to gather evidence of its beginnings.
China's foreign minister has dismissed the report as "anti-science".
The report from the Office of the Director of National Intelligence said the intelligence community remains divided on Covid's most likely origin.
"All agencies assess that two hypotheses are plausible: natural exposure to an infected animal and a laboratory-associated incident."
According to the report, several unnamed spy agencies thought Covid emerged from "natural exposure to an animal infected with it or a close progenitor virus". But they only had "low confidence" in this conclusion.
One intelligence agency developed "moderate confidence" that the first human infection was likely due a "laboratory-associated incident" at the Wuhan Institute of Virology, which has studied coronaviruses in bats for more than a decade.
For the Definitely Dreaming week 39 theme of “Square” an image of my latest purchase, an Aranet 4 CO₂ monitor.
Knowing the CO₂ level in the inside air will help you protect yourself and others from getting COVID-19 or other respiratory diseases. It will also help you avoid excessive sleepiness and poor concentration from high CO₂ levels.
We all breathe in oxygen and breathe out CO₂, which means the CO₂ level in an indoor space increases over time, depending how many people there are in the room and how well it is ventilated.
That means the CO₂ level in an indoor space gives an idea of how fresh or stale the air is.
If the CO₂ level is too high, it means the air is stale and the space needs more ventilation.
The more stale the air is, the greater the number of germs, such as coronaviruses, in each breath, so the more likely you are to become ill.
As well as increasing the chance of catching an infectious illness, a high CO₂ level makes you sleepy and affects your ability to do complex tasks.
If interested and in Australia, I can highly recommend CO2radical.com.au who had these for $30 cheaper than Amazon, with free shipping and delivered in a couple of days.
The first task for mine is to lend it to my daughter to try and assess the situation in her classroom (she is a teacher).
Helicopter shot of a portion of the Paria Plateau largely unknown. If all goes well, I hope to be looking around out here this week, well isolated from coronaviruses.
I've seen those rocks on the right side, but what is farther out to the west and north? Maybe I'll find something interesting. That's not a road out there, but a long sand bar. I'll have to walk a ways to get out there. From past experience, there's usually something pretty interesting to see.
Report May 3, 2020: I visited some things in the bottom half of this photo, but warm weather made hiking tiresome. I did find some pretty amazing things out of frame at bottom, and I explored other fascinating areas in and around the plateau.
Severe acute respiratory syndrome coronavirus 2 based on the CDC's computer rendering.
Visible is the exterior of the viral lipid envelope (grey), the Membrane (M) protein (orange), the Envelope (E) protein (yellow) and the characteristic SARS-CoV-2 Glycoprotein Spike (S) proteins (red).
Science for anyone interested:
Lipid envelopes facilitate virus entry into host cells by membrane fusion, help with immune evasion, and provide additional protection for the viral genome (consisting of positive-sense RNA within a helical nucleocapsid in SARS-CoV-2). Washing your hands with soap inactivates viruses by disrupting this lipid bilayer.
Coronavirus M protein is essential for packing and assembly of viral components during the formation of virions. It also has a structural role and may contribute to viral pathology through immune dysregulation.
Coronavirus E protein forms a pentameric ion channel (represented by 5-petal flowers) known as a viroporin. These increase the permeability of the host cell membranes to aid with budding of virions from the golgi and release from cells. The E protein is also believed to assist the M protein in viral assembly.
Coronavirus Spike proteins are the characteristic surface antigens of coronaviruses from which they derive their name.
These proteins have a trimeric structure represented here using tricorns.
It will likely be the main target for vaccine development.
The spike proteins' most important function is to mediate viral attachment to host cell receptors and therefore it also confers tissue and host species specificity. In the case of SARS-Cov-2 (and its predecessor SARS-CoV) the spike proteins bind to human ACE2 (angiotensin converting enzyme 2), an enzyme involved in control of blood pressure and vascular homeostasis, which is most highly expressed on the surface membranes of cells in the kidneys, heart and lungs.
Since the lungs are easily accessible through inhalation of virions, SARS-CoV-2 commonly causes lower respiratory tract infections. Cells of the alveoli, which enable gas exchange between the air and the blood, are particularly affected and are lysed as newly produced virions burst out of their host cells. This causes damage to the alveoli which attracts immune cells leading to inflammation which further damages the alveoli. Inflamed alveoli fill with fluid (pneumonia) which prevents efficient gas exchange causing the shortness of breath commonly seen in patients, while irritation of nerves in the inflamed tissue results in the dry cough, helping to further transmit the virus. Severe cases of viral pneumonia may lead to secondary infections (eg. bacterial) and are the main cause of COVID-19 deaths.
If you made it this far you're an absolute mad lad.
Can face masks help slow the spread of the coronavirus (SARS-CoV-2) that causes COVID-19? Yes. Face masks combined with other preventive measures, such as getting vaccinated, frequent hand-washing and physical distancing, can help slow the spread of the virus. The U.S. Centers for Disease Control and Prevention (CDC) recommends fabric masks for the general public. People who haven’t been fully vaccinated should continue to wear face masks in indoor public places and outdoors where there is a high risk of COVID-19 transmission, such as crowded events or large gatherings. The CDC says that N95 masks should be reserved for health care providers. How do the different types of masks work? Medical masks Also called surgical masks, these are loosefitting disposable masks. They're meant to protect the wearer from contact with droplets and sprays that may contain germs. A medical mask also filters out large particles in the air when the wearer breathes in. To make medical masks more form-fitting, knot the ear loops where they attach to the mask. Then fold and tuck the unneeded material under the edges.
An N95 mask is a type of respirator. It offers more protection than a medical mask does because it filters out both large and small particles when the wearer inhales. Because N95 masks have been in short supply, the CDC has said they should be reserved for health care providers. Health care providers must be trained and pass a fit test before using an N95 mask. Like surgical masks, N95 masks are intended to be disposable. However, researchers are testing ways to disinfect and reuse them. Some N95 masks, and even some cloth masks, have valves that make them easier to breathe through. Unfortunately, these masks don't filter the air the wearer breathes out. For this reason, they've been banned in some places. A cloth mask is intended to trap respiratory droplets that are released when the wearer talks, coughs or sneezes. It also acts as a barrier to protect the wearer from inhaling droplets released by others.
The most effective cloths masks are made of multiple layers of tightly woven fabric like cotton. A mask with layers will stop more droplets from getting through your mask or escaping from it. How to get the most from your mask; The effectiveness of cloth and medical masks can be improved by ensuring that the masks are well fitted to the contours of your face to prevent leakage of air around the masks' edges. Masks should be snug over the nose, mouth and chin, with no gaps. You should feel warm air coming through the front of the mask when you breathe out. You shouldn't feel air coming out under the edges of the mask. Masks that have a bendable nose strip help prevent air from leaking out of the top of the mask. Some people choose to wear a disposable mask under their cloth mask. In that case, the cloth mask should press the edges of the disposable mask against the face. Don't add layers if they make it hard to breathe or obstruct your vision. Proper use, storage and cleaning of masks also affects how well they protect you. Follow these steps for putting on and taking off your mask: Wash or sanitize your hands before and after putting on your mask. Place your mask over your mouth and nose and chin. Tie it behind your head or use ear loops. Make sure it's snug.,Don't touch your mask while wearing it. If you accidentally touch your mask, wash or sanitize your hands. If your mask becomes wet or dirty, switch to a clean one. Put the used mask in a sealable bag until you can get rid of it or wash it. Remove the mask by untying it or lifting off the ear loops without touching the front of the mask or your face.
Wash your hands immediately after removing your mask.
Regularly wash cloth masks in the washing machine or by hand. (They can be washed along with other laundry.)
And don't forget these precautions: Don't put masks on anyone who has trouble breathing or is unconscious or otherwise unable to remove the mask without help. Don't put masks on children under 2 years of age. Don't use face masks as a substitute for physical distancing. What about face shields? The CDC doesn't recommend using face shields instead of masks because it's unclear how much protection shields provide. However, wearing a face mask may not be possible in every situation. If you must use a face shield instead of a mask, choose one that wraps around the sides of your face and extends below your chin.
Do you still need to wear a facemask after you’re fully vaccinated? After you're fully vaccinated, the CDC recommends that it's ok not to wear a mask except where required by a rule or law. However, if you are in an area with a high number of new COVID-19 cases in the last week, the CDC recommends wearing a mask indoors in public and outdoors in crowded areas or when you are in close contact with unvaccinated people. If you are fully vaccinated and have a condition or are taking medications that weaken your immune system, you may need to keep wearing a mask. You're considered fully vaccinated 2 weeks after you get a second dose of an mRNA COVID-19 vaccine or 2 weeks after you get a single dose of the Janssen/Johnson & Johnson COVID-19 vaccine. In the U.S., everyone also needs to wear a mask while on planes, buses, trains and other forms of public transportation. The World Health Organization (WHO) recommends medical masks for health care workers as well as for anyone who has or may have COVID-19 or who is caring for someone who has or may have COVID-19.``
www.mayoclinic.org/diseases-conditions/coronavirus/in-dep...
The Covid-19 pandemic seems to have sorted us into three types based on our attitudes toward masking: Call them nervous maskers, never-maskers and uncertain maskers. The first feel guilty or nervous about unmasking, so they tend to default to wearing masks; the second feel angry and resentful about being told to mask, so they often refuse entirely. And the third group is just trying to do the right thing without a lot of certainty one way or another. Winter is coming, with its continued battles against delta or mu or another variant. We have better protections now (vaccinations, natural antibodies) but also are returning to higher-risk environments (nightclubs, offices, schools). To complicate matters, there are additional factors to consider such as waning immunity from vaccines and the potential of a bad flu season.
Fortunately, there have been a number of important studies on the efficacy of masking over the past 18 months. The good news is that the research suggests most of us can actually de-mask without guilt or worry in many instances — and not just outdoors. It tells us, for example, that plexiglass dividers are in most cases useless or worse. But relaxed refuseniks need a rethink, too — we shouldn’t be ditching masks entirely. On the contrary, the more people adopt a policy of tactical masking, taking situational factors into account, the lower the infection risk and the more freedoms we can enjoy again. As the probability of infection increases, mask wearers lower the risk of catching the virus compared with no masking. For N95 or FFP2 masks, the protection is far greater. Note: Relative reduction in risk-of-infection figures are for an infection probability of 4%.
It’s no wonder we’re either nervous, angry or confused about masks when you consider how masking guidance and conventions have been all over the map. It seems amazing now that the Centers for Disease Control and Prevention, the World Health Organization and various governments had warned against using masks in the early days of the pandemic. When Thomas Nitzsche, mayor of Jena, Germany, made the decision to require masks in public in early April 2020, his city became one of the first to do so. Infections dropped by up to 75% over the next few weeks. In May, the CDC said fully vaccinated people no longer needed to wear masks in most public settings. Two months later, as delta variant cases rose, the CDC revised that guidance. Now seven U.S. states — Hawaii, Illinois, Louisiana, Nevada, New Mexico, Oregon and Washington — require most people to wear masks indoors in public places. Some states, including Texas and Florida, bar local authorities from imposing Covid-19 restrictions, including mask-wearing. In places that view masking as an affront to liberty, university professors can’t even ask students to wear masks during office hours without putting their jobs at risk. In England, there was a general lifting of restrictions in July, though U.K. Health Secretary Sajid Javid said last week that masking may become mandatory again in some indoor settings this winter, depending mainly on whether hospitalizations from Covid spike. While masks are required on public transport, I’d say about half or fewer comply during my journeys. Many offices require workers to mask while walking around, but few Tory lawmakers are wearing them in the House of Commons. Scotland still requires masks to be worn in shops and restaurants while not seated, as well as on public transport. Berlin requires the medical-grade FFP2 masks on public transport. Certain regions of France also have masking requirements in place. But if you care about what the evidence says (and some people don’t), the jury is in: Masks help a lot. Take, for example, the study that shows most U.S. states that had high mask usage in one month avoided high Covid rates in the subsequent month, even after adjusting for masking policy, social-distancing policy and demographic factors. The majority of states with low mask usage ended up with high Covid case rates. Note: Low mask adherence means states that fall below the 25th percentile; high adherence are those states above the 75th percentile. Study analyzed data from April to October 2020.
The largest study yet on the effectiveness of masking, posted online in pre-print earlier this month, was a randomize trial conducted in 600 villages across Bangladesh covering a population of more than 340,000 adults. It offered strong evidence that masks, and surgical masks in particular, reduce virus transmission. Researchers found that a 29 percentage-point increase in mask adoption led to an 11% reduction in symptomatic SARS-CoV-2 prevalence, where surgical masks were distributed; and a 35% reduction in people over 60. Symptom reductions using surgical masks were not statistically significant in younger age groups. While vaccines have largely broken the link between infections and hospitalizations (and death), they haven’t eliminated the need for mask-wearing. Data released last week showed that two doses of the Oxford/AstraZeneca vaccine were 67% effective against delta-variant infections (compared with 80% for two doses of Pfizer/BioNTech’s). Infections can still be nasty; long Covid remains another reason for vigilance. Not only can fully vaccinated people catch and transmit the virus, but it is unvaccinated adults who are more mask-resistant. Since it’s estimated that around half of all transmissions come from asymptomatic persons, masks are still key to preventing infections. But masking shouldn’t be performative, as it often is with those uncertain maskers who just want to show they are being thoughtful. Which masks we wear, and especially how they fit, is important. Mind the Gap . While N95s offer a higher level of protection, a well-fitted surgical mask blocks most particles.
More particles get through mask; Of course, not all masks are created equal, as a recent study published in the journal Nature highlighted. The authors measured the thermal behavior of face masks in real time during inhalation and exhalation to determine the relationship between the fabric structure of the masks and their performance. Their experiment helped shed light on how aerosol-containing bacteria and coronaviruses penetrate three different kinds of masks — reusable face masks, disposable surgical masks and the N95 — and how we can evaluate air filtration performance.Reusable masks have longer, thicker fibers with a larger average pore diameter. Unsurprisingly, they have
higher levels of permeability, with the surgical mask coming second, followed by the F95 (similar to the FFP2 in Europe). Those findings should even help manufacturers create a new generation of masks that offer more breathability while also improving filtration. The CDC doesn’t recommend scarves and other headwear because they tend to be made from loosely woven fabrics. Loosely Denser fabrics such as cotton with a 600 thread count compared with cotton that is woven with 80 threads per inch, are much more effective. Mixed fabrics also tend to have better results. A study on masks with and without gaps shows that leaks can significantly reduce their effectiveness. In addition to materials, layering them can also improve efficacy. New lab evidence on different kinds of masks showed that a three-ply surgical mask blocked 42% of particles from a simulated cough; a three-ply cloth mask was pretty similar. But the protection jumped to 92% when a cloth mask was worn over a surgical mask. Comfort is important to being able to wear a mask for long periods of time. In addition to metal nose-bridge strips that can help a mask stay on better, straps that tie behind the head and mask extenders can help reduce soreness around the ears. Insertable filters can be replaced when masks get wet.
Masks will also help prevent more vaccine-resistant variants from emerging as well as higher rates of flu infections, which can also cause serious illness and even death. Even so, the research strips away some of the mask myths and can help all categories of maskers — nervous, nevers and uncertains — be more tactical and aware. To know whether a mask is a must-have, a good idea or entirely superfluous, check the risk factors the way you might a weather report in the mountains: How densely packed and how well-ventilated is the space you are entering? Will you be moving around or stationary? It’s certainly good to mask up in an elevator or on public transport where people are pretty close together. It’s probably not necessary in an open-planned, well-ventilated office, provided people observe a measure of social distancing. Then be mindful of the infection and vaccination rates where you are. If you are in Broward County, Florida, where 70% of over-18s are vaccinated, you’d be justified in having a more relaxed approach; drive next door to Glades County, where only 31% are vaccinated and infection rates are high, and you’ll want to be more vigilant. Similarly only 16% of over-65s in King County, Texas, are vaccinated compared with 70% next door in Knox County, where the CDC recommends even vaccinated people mask. By moving beyond the “hygiene theater” of practices that don’t offer much benefit while also accepting that there are many different levels of risk tolerance and factors that increase or lower situational risk, we can treat masking a little like checking the weather forecast. Some days require a little more covering up than others.
www.bloomberg.com/graphics/2021-opinion-how-to-wear-face-...
The 1918–20 "Spanish flu" influenza pandemic resulted in dramatic mortality worldwide.
A pandemic (from Greek πᾶν, pan, 'all' and δῆμος, demos, 'people') is an epidemic of disease that has spread across a large region, for instance multiple continents, or worldwide. A widespread endemic disease with a stable number of infected people is not a pandemic. Further, flu pandemics generally exclude recurrences of seasonal flu.
Throughout history, there have been a number of pandemics of diseases such as smallpox and tuberculosis. One of the most devastating pandemics was the Black Death (also known as The Plague), which killed an estimated 75–200 million people in the 14th century. Other notable pandemics include the 1918 influenza pandemic (Spanish flu) and the 2009 flu pandemic (H1N1). Current pandemics include HIV/AIDS and the 2019–20 coronavirus pandemic.
Contents
1Definition and stages
2Management
3Current pandemics
3.1HIV/AIDS
3.2Coronavirus disease 2019 (COVID-19)
4Notable outbreaks
4.1Cholera
4.2Influenza
4.3Typhus
4.4Smallpox
4.5Measles
4.6Tuberculosis
4.7Leprosy
4.8Malaria
4.9Yellow fever
5Concerns about future pandemics
5.1Antibiotic resistance
5.2Viral hemorrhagic fevers
5.3Coronaviruses
5.4Influenza
5.5Zika virus
6Economic consequences
7Biological warfare
8In popular culture
9See also
10Notes
11References
12Further reading
13External links
Definition and stages[edit]
The World Health Organization's former influenza pandemic alert phases—WHO no longer uses this old system of six phases
A pandemic is an epidemic occurring on a scale that crosses international boundaries, usually affecting people on a worldwide scale.[1] Pandemics can also occur in important agricultural organisms (livestock, crop plants, fish, tree species) or in other organisms.[citation needed] A disease or condition is not a pandemic merely because it is widespread or kills many people; it must also be infectious. For instance, cancer is responsible for many deaths but is not considered a pandemic because the disease is neither infectious nor contagious.[2]
The World Health Organization (WHO) previously applied a six-stage classification to describe the process by which a novel influenza virus moves from the first few infections in humans through to a pandemic. This starts with the virus mostly infecting animals, with a few cases where animals infect people, then moves through the stage where the virus begins to spread directly between people and ends with a pandemic when infections from the new virus have spread worldwide. In February 2020, a WHO spokesperson clarified that "there is no official category [for a pandemic]".[a][3]
In a virtual press conference in May 2009 on the influenza pandemic, Dr. Keiji Fukuda, Assistant Director-General ad interim for Health Security and Environment, WHO said "An easy way to think about pandemic ... is to say: a pandemic is a global outbreak. Then you might ask yourself: 'What is a global outbreak'? Global outbreak means that we see both spread of the agent ... and then we see disease activities in addition to the spread of the virus."[4]
In planning for a possible influenza pandemic, the WHO published a document on pandemic preparedness guidance in 1999, revised in 2005 and in February 2009, defining phases and appropriate actions for each phase in an aide-mémoire titled WHO pandemic phase descriptions and main actions by phase. The 2009 revision, including definitions of a pandemic and the phases leading to its declaration, were finalized in February 2009. The pandemic H1N1 2009 virus was neither on the horizon at that time nor mentioned in the document.[5][6] All versions of this document refer to influenza. The phases are defined by the spread of the disease; virulence and mortality are not mentioned in the current WHO definition, although these factors have previously been included.[7]
Management[edit]
See also: Mathematical modelling of infectious disease
The goals of community mitigation: (1) delay outbreak peak; (2) reduce peak burden on healthcare, known as flattening the curve; and (3) diminish overall cases and health impact.[8][9]
The basic strategies in the control of an outbreak are containment and mitigation. Containment may be undertaken in the early stages of the outbreak, including contact tracing and isolating infected individuals to stop the disease from spreading to the rest of the population, other public health interventions on infection control, and therapeutic countermeasures such as vaccinations which may be effective if available.[10] When it becomes apparent that it is no longer possible to contain the spread of the disease, it will then move on to the mitigation stage, when measures are taken to slow the spread of disease and mitigate its effects on the health care system and society. In reality, a combination of both containment and mitigation measures may be undertaken at the same time to control an outbreak.[11]
A key part of managing an infectious disease outbreak is trying to decrease the epidemic peak, known as flattening the epidemic curve.[8] This helps decrease the risk of health services being overwhelmed and providing more time for a vaccine and treatment to be developed.[8] Non-pharmaceutical interventions may be taken to manage the outbreak; for example in a flu pandemic, these actions may include personal preventive measures such as hand hygiene, wearing face-masks and self-quarantine; community measures aimed at social distancing such as closing schools and cancelling mass gathering events; community engagement to encourage acceptance and participation in such interventions; as well as environmental measures such as cleaning of surfaces.[9]
Another strategy, suppression, requires more extreme long-term non-pharmaceutical interventions so as to reverse the pandemic by reducing the basic reproduction number to less than 1. The suppression strategy, which include stringent population-wide social distancing, home isolation of cases and household quarantine, was undertaken by China during the 2019–20 coronavirus pandemic where entire cities were placed under lockdown, but such strategy carries with it considerable social and economic costs.[12]
Current pandemics[edit]
HIV/AIDS[edit]
Main article: AIDS pandemic
Estimated HIV/AIDS prevalence among young adults (15-49) by country as of 2008
HIV originated in Africa, and spread to the United States via Haiti between 1966 and 1972.[13] AIDS is currently a pandemic, with infection rates as high as 25% in southern and eastern Africa. In 2006, the HIV prevalence rate among pregnant women in South Africa was 29%.[14] Effective education about safer sexual practices and bloodborne infection precautions training have helped to slow down infection rates in several African countries sponsoring national education programs.[citation needed]
Coronavirus disease 2019 (COVID-19)[edit]
Main article: 2019–20 coronavirus pandemic
People queueing outside a Wuhan pharmacy to buy face masks and medical supplies
A new coronavirus was first identified in Wuhan, Hubei province, China, in late December 2019,[15] as causing a cluster of cases of an acute respiratory disease, referred to as coronavirus disease 2019 (COVID-19). According to media reports, more than 200 countries and territories have been affected, with major outbreaks in the United States, central China, Italy, Spain, and Iran.[16][17] On 11 March 2020, the World Health Organization characterized the spread of COVID-19 as a pandemic.[18][19] As of 3 April 2020, the number of SARS-CoV-2 infected persons reached one million, the death toll was 55,132 and the number of patients recovered was 225,335.[20]
Notable outbreaks[edit]
See also: List of epidemics, Columbian Exchange, and Globalization and disease
There have been a number of significant epidemics and pandemics recorded in human history, generally zoonoses such as influenza and tuberculosis, which came about with domestication of animals. There have been a number of particularly significant epidemics that deserve mention above the "mere" destruction of cities:
Plague of Athens, from 430 to 426 BCE. During the Peloponnesian War, typhoid fever killed a quarter of the Athenian troops, and a quarter of the population over four years. This disease fatally weakened the dominance of Athens, but the sheer virulence of the disease prevented its wider spread; i.e. it killed off its hosts at a rate faster than they could spread it. The exact cause of the plague was unknown for many years. In January 2006, researchers from the University of Athens analyzed teeth recovered from a mass grave underneath the city, and confirmed the presence of bacteria responsible for typhoid.[21]
Contemporary engraving of Marseille during the Great Plague of Marseille in 1720–1721
Antonine Plague, from 165 to 180 AD. Possibly smallpox brought to the Italian peninsula by soldiers returning from the Near East; it killed a quarter of those infected, and up to five million in all.[22] At the height of a second outbreak, the Plague of Cyprian (251–266), which may have been the same disease, 5,000 people a day were said to be dying in Rome.
Plague of Justinian, from 541 to 750, was the first recorded outbreak of the bubonic plague. It started in Egypt, and reached Constantinople the following spring, killing (according to the Byzantine chronicler Procopius) 10,000 a day at its height, and perhaps 40% of the city's inhabitants. The plague went on to eliminate a quarter to half the human population of the known world.[23][24] It caused Europe's population to drop by around 50% between 550 AD and 700 AD.[25]
Black Death, from 1331 to 1353. The total number of deaths worldwide is estimated at 75 to 200 million people.Black Death#cite ref-ABC/Reuters 1-1 Eight hundred years after the last outbreak, the plague returned to Europe. Starting in Asia, the disease reached Mediterranean and western Europe in 1348 (possibly from Italian merchants fleeing fighting in Crimea), and killed an estimated 20 to 30 million Europeans in six years;[26] a third of the total population,[27] and up to a half in the worst-affected urban areas.[28] It was the first of a cycle of European plague epidemics that continued until the 18th century.[29] There were more than 100 plague epidemics in Europe in this period.[30] The disease recurred in England every two to five years from 1361 to 1480.[31] By the 1370s, England's population was reduced by 50%.[32] The Great Plague of London of 1665–66 was the last major outbreak of the plague in England. The disease killed approximately 100,000 people, 20% of London's population.[33]
The third plague pandemic started in China in 1855, and spread to India, where 10 million people died.[34] During this pandemic, the United States saw its first outbreak: the San Francisco plague of 1900–1904.[35] Today, isolated cases of plague are still found in the western United States.[36]
Spanish flu, from 1918 to 1920. It infected 500 million people around the world,[37] including people on remote Pacific islands and in the Arctic, and resulted in the deaths of 50 to 100 million people.[37][38] Most influenza outbreaks disproportionately kill the very young and the very old, with higher survival rate for those in between, but the Spanish flu had an unusually high mortality rate for young adults.[39] Spanish flu killed more people than World War I did and it killed more people in 25 weeks than AIDS did in its first 25 years.[40][41] Mass troop movements and close quarters during World War I caused it to spread and mutate faster; the susceptibility of soldiers to Spanish flu might have been increased due to stress, malnourishment and chemical attacks.[42] Improved transportation systems made it easier for soldiers, sailors, and civilian travelers to spread the disease.[43]
Aztecs dying of smallpox, Florentine Codex (compiled 1540–1585)
Encounters between European explorers and populations in the rest of the world often introduced local epidemics of extraordinary virulence. Disease killed part of the native population of the Canary Islands in the 16th century (Guanches). Half the native population of Hispaniola in 1518 was killed by smallpox. Smallpox also ravaged Mexico in the 1520s, killing 150,000 in Tenochtitlán alone, including the emperor, and Peru in the 1530s, aiding the European conquerors.[44] Measles killed a further two million Mexican natives in the 17th century. In 1618–1619, smallpox wiped out 90% of the Massachusetts Bay Native Americans.[45] During the 1770s, smallpox killed at least 30% of the Pacific Northwest Native Americans.[46] Smallpox epidemics in 1780–1782 and 1837–1838 brought devastation and drastic depopulation among the Plains Indians.[47] Some believe the death of up to 95% of the Native American population of the New World was caused by Old World diseases such as smallpox, measles, and influenza.[48] Over the centuries, the Europeans had developed high degrees of immunity to these diseases, while the indigenous peoples had no such immunity.[49]
Smallpox devastated the native population of Australia, killing around 50% of Indigenous Australians in the early years of British colonisation.[50] It also killed many New Zealand Māori.[51] As late as 1848–49, as many as 40,000 out of 150,000 Hawaiians are estimated to have died of measles, whooping cough and influenza. Introduced diseases, notably smallpox, nearly wiped out the native population of Easter Island.[52] Measles killed more than 40,000 Fijians, approximately one-third of the population, in 1875,[53] and in the early 21st century devastated the Andamanese population.[54] The Ainu population decreased drastically in the 19th century, due in large part to infectious diseases brought by Japanese settlers pouring into Hokkaido.[55]
Researchers concluded that syphilis was carried from the New World to Europe after Columbus' voyages. The findings suggested Europeans could have carried the nonvenereal tropical bacteria home, where the organisms may have mutated into a more deadly form in the different conditions of Europe.[56] The disease was more frequently fatal than it is today. Syphilis was a major killer in Europe during the Renaissance.[57] Between 1602 and 1796, the Dutch East India Company sent almost a million Europeans to work in Asia. Ultimately, fewer than a third made their way back to Europe. The majority died of diseases.[58] Disease killed more British soldiers in India and South Africa than war.[59]
As early as 1803, the Spanish Crown organized a mission (the Balmis expedition) to transport the smallpox vaccine to the Spanish colonies, and establish mass vaccination programs there.[60] By 1832, the federal government of the United States established a smallpox vaccination program for Native Americans.[61] From the beginning of the 20th century onwards, the elimination or control of disease in tropical countries became a driving force for all colonial powers.[62] The sleeping sickness epidemic in Africa was arrested due to mobile teams systematically screening millions of people at risk.[63] In the 20th century, the world saw the biggest increase in its population in human history due to lessening of the mortality rate in many countries due to medical advances.[64] The world population has grown from 1.6 billion in 1900 to an estimated 6.8 billion in 2011.[65]
Cholera[edit]
Main article: Cholera outbreaks and pandemics
Since it became widespread in the 19th century, cholera has killed tens of millions of people.[66]
1817–1824 cholera pandemic. Previously restricted to the Indian subcontinent, the pandemic began in Bengal, then spread across India by 1820. 10,000 British troops and countless Indians died during this pandemic.[67] It extended as far as China, Indonesia (where more than 100,000 people succumbed on the island of Java alone) and the Caspian Sea before receding. Deaths in the Indian subcontinent between 1817 and 1860 are estimated to have exceeded 15 million persons. Another 23 million died between 1865 and 1917. Russian deaths during a similar period exceeded 2 million.[68]
1826–1837 cholera pandemic. Reached Russia (see Cholera Riots), Hungary (about 100,000 deaths) and Germany in 1831, London in 1832 (more than 55,000 persons died in the United Kingdom),[69] France, Canada (Ontario), and United States (New York City) in the same year,[70] and the Pacific coast of North America by 1834. It is believed that more than 150,000 Americans died of cholera between 1832 and 1849.[71]
1846–1860 cholera pandemic. Deeply affected Russia, with more than a million deaths. A two-year outbreak began in England and Wales in 1848 and claimed 52,000 lives.[72] Throughout Spain, cholera caused more than 236,000 deaths in 1854–55.[73] It claimed 200,000 lives in Mexico.[74]
1863–75 cholera pandemic. Spread mostly in Europe and Africa. At least 30,000 of the 90,000 Mecca pilgrims fell victim to the disease. Cholera claimed 90,000 lives in Russia in 1866.[75]
In 1866, there was an outbreak in North America. It killed some 50,000 Americans.[71]
1881–96 cholera pandemic. The 1883–1887 epidemic cost 250,000 lives in Europe and at least 50,000 in the Americas. Cholera claimed 267,890 lives in Russia (1892);[76] 120,000 in Spain;[77] 90,000 in Japan and 60,000 in Persia.
In 1892, cholera contaminated the water supply of Hamburg, and caused 8,606 deaths.[78]
1899–1923 cholera pandemic. Had little effect in Europe because of advances in public health, but Russia was badly affected again (more than 500,000 people dying of cholera during the first quarter of the 20th century).[79] The sixth pandemic killed more than 800,000 in India. The 1902–1904 cholera epidemic claimed more than 200,000 lives in the Philippines.[80]
1961–75 cholera pandemic. Began in Indonesia, called El Tor after the new biotype responsible for the pandemic, and reached Bangladesh in 1963, India in 1964, and the Soviet Union in 1966. Since then the pandemic has reached Africa, South America, and Central America.
Influenza[edit]
Main article: Influenza pandemic
Advice for travelers (in French and English) on the risks of epidemics abroad; posters from the Charles De Gaulle airport, Paris
The Greek physician Hippocrates, the "Father of Medicine", first described influenza in 412 BC.[81]
The first influenza pandemic was recorded in 1580, and since then, influenza pandemics occurred every 10 to 30 years.[82][83][84]
The 1889–1890 flu pandemic, also known as Russian Flu, was first reported in May 1889 in Bukhara, Uzbekistan. By October, it had reached Tomsk and the Caucasus. It rapidly spread west and hit North America in December 1889, South America in February–April 1890, India in February–March 1890, and Australia in March–April 1890. The H3N8 and H2N2 subtypes of the Influenza A virus have each been identified as possible causes. It had a very high attack and mortality rate, causing around a million fatalities.[85]
The "Spanish flu", 1918–1919. First identified early in March 1918 in U.S. troops training at Camp Funston, Kansas. By October 1918, it had spread to become a worldwide pandemic on all continents, and eventually infected about one-third of the world's population (or ≈500 million persons).[37] Unusually deadly and virulent, it ended almost as quickly as it began, vanishing completely within 18 months. Within six months, some 50 million people were dead;[37] some estimates put the total number of fatalities worldwide at over twice that number.[86] About 17 million died in India, 675,000 in the United States,[87] and 200,000 in the United Kingdom. The virus that caused Spanish flu was also implicated as a cause of encephalitis lethargica in children.[88] The virus was recently reconstructed by scientists at the CDC studying remains preserved by the Alaskan permafrost. The H1N1 virus has a small but crucial structure that is similar to the Spanish flu.[89]
The "Asian Flu", 1957–58. A H2N2 virus first identified in China in late February 1957. It caused about two million deaths globally.[90] The Asian flu spread to the United States by June 1957 and caused about 70,000 deaths in the U.S.
The "Hong Kong Flu", 1968–69. A H3N2 virus first detected in Hong Kong in early 1968, and spread to the United States later that year. This pandemic of 1968 and 1969 killed approximately one million people worldwide.[91] It caused about 34,000 deaths in the United States.
The "Swine Flu", 2009–10. An H1N1 virus first detected in Mexico in early 2009, and spread to the United States later that year. This pandemic was estimated to have killed around 284,000 people worldwide.[92][failed verification] It was estimated to have caused about 12,000 deaths in the United States alone.
Typhus[edit]
Typhus is sometimes called "camp fever" because of its pattern of flaring up in times of strife. (It is also known as "gaol fever" and "ship fever", for its habits of spreading wildly in cramped quarters, such as jails and ships.) Emerging during the Crusades, it had its first impact in Europe in 1489, in Spain. During fighting between the Christian Spaniards and the Muslims in Granada, the Spanish lost 3,000 to war casualties, and 20,000 to typhus. In 1528, the French lost 18,000 troops in Italy, and lost supremacy in Italy to the Spanish. In 1542, 30,000 soldiers died of typhus while fighting the Ottomans in the Balkans.
During the Thirty Years' War (1618–1648), about eight million Germans were killed by bubonic plague and typhus.[93] The disease also played a major role in the destruction of Napoleon's Grande Armée in Russia in 1812. During the retreat from Moscow, more French military personnel died of typhus than were killed by the Russians.[94] Of the 450,000 soldiers who crossed the Neman on 25 June 1812, fewer than 40,000 returned. More military personnel were killed from 1500–1914 by typhus than from military action.[95] In early 1813, Napoleon raised a new army of 500,000 to replace his Russian losses. In the campaign of that year, more than 219,000 of Napoleon's soldiers died of typhus.[96] Typhus played a major factor in the Irish Potato Famine. During World War I, typhus epidemics killed more than 150,000 in Serbia. There were about 25 million infections and 3 million deaths from epidemic typhus in Russia from 1918 to 1922.[96] Typhus also killed numerous prisoners in the Nazi concentration camps and Soviet prisoner of war camps during World War II. More than 3.5 million Soviet POWs died out of the 5.7 million in Nazi custody.[97]
Smallpox[edit]
A child with smallpox infection, c. 1908
Smallpox was a contagious disease caused by the variola virus. The disease killed an estimated 400,000 Europeans per year during the closing years of the 18th century.[98] During the 20th century, it is estimated that smallpox was responsible for 300–500 million deaths.[99][100] As recently as the early 1950s, an estimated 50 million cases of smallpox occurred in the world each year.[101] After successful vaccination campaigns throughout the 19th and 20th centuries, the WHO certified the eradication of smallpox in December 1979. To this day, smallpox is the only human infectious disease to have been completely eradicated,[102] and one of two infectious viruses ever to be eradicated along with rinderpest.[103]
Measles[edit]
Historically, measles was prevalent throughout the world, as it is highly contagious. According to the U.S. National Immunization Program, 90% of people were infected with measles by age 15. Before the vaccine was introduced in 1963, there were an estimated three to four million cases in the U.S. each year.[104] Measles killed around 200 million people worldwide over the last 150 years.[105] In 2000 alone, measles killed some 777,000 worldwide out of 40 million cases globally.[106]
Measles is an endemic disease, meaning it has been continually present in a community, and many people develop resistance. In populations that have not been exposed to measles, exposure to a new disease can be devastating. In 1529, a measles outbreak in Cuba killed two-thirds of the natives who had previously survived smallpox.[107] The disease had ravaged Mexico, Central America, and the Inca civilization.[108]
Tuberculosis[edit]
In 2007, the prevalence of TB per 100,000 people was highest in Sub-Saharan Africa, and was also relatively high in Asian countries like India.
One-quarter of the world's current population has been infected with Mycobacterium tuberculosis, and new infections occur at a rate of one per second.[109] About 5–10% of these latent infections will eventually progress to active disease, which, if left untreated, kills more than half its victims. Annually, eight million people become ill with tuberculosis, and two million die from the disease worldwide.[110] In the 19th century, tuberculosis killed an estimated one-quarter of the adult population of Europe;[111] by 1918, one in six deaths in France were still caused by tuberculosis. During the 20th century, tuberculosis killed approximately 100 million people.[105] TB is still one of the most important health problems in the developing world.[112]
Leprosy[edit]
Leprosy, also known as Hansen's disease, is caused by a bacillus, Mycobacterium leprae. It is a chronic disease with an incubation period of up to five years. Since 1985, 15 million people worldwide have been cured of leprosy.[113]
Historically, leprosy has affected people since at least 600 BC.[114] Leprosy outbreaks began to occur in Western Europe around 1000 AD.[115][116] Numerous leprosoria, or leper hospitals, sprang up in the Middle Ages; Matthew Paris estimated that in the early 13th century, there were 19,000 of them across Europe.[117]
Malaria[edit]
Past and current malaria prevalence in 2009
Malaria is widespread in tropical and subtropical regions, including parts of the Americas, Asia, and Africa. Each year, there are approximately 350–500 million cases of malaria.[118] Drug resistance poses a growing problem in the treatment of malaria in the 21st century, since resistance is now common against all classes of antimalarial drugs, except for the artemisinins.[119]
Malaria was once common in most of Europe and North America, where it is now for all purposes non-existent.[120] Malaria may have contributed to the decline of the Roman Empire.[121] The disease became known as "Roman fever".[122] Plasmodium falciparum became a real threat to colonists and indigenous people alike when it was introduced into the Americas along with the slave trade. Malaria devastated the Jamestown colony and regularly ravaged the South and Midwest of the United States. By 1830, it had reached the Pacific Northwest.[123] During the American Civil War, there were more than 1.2 million cases of malaria among soldiers of both sides.[124] The southern U.S. continued to be afflicted with millions of cases of malaria into the 1930s.[125]
Yellow fever[edit]
Yellow fever has been a source of several devastating epidemics.[126] Cities as far north as New York, Philadelphia, and Boston were hit with epidemics. In 1793, one of the largest yellow fever epidemics in U.S. history killed as many as 5,000 people in Philadelphia—roughly 10% of the population. About half of the residents had fled the city, including President George Washington.[127] In colonial times, West Africa became known as "the white man's grave" because of malaria and yellow fever.[128]
Concerns about future pandemics[edit]
See also: Pandemic prevention
Antibiotic resistance[edit]
Main article: Antibiotic resistance
Antibiotic-resistant microorganisms, sometimes referred to as "superbugs", may contribute to the re-emergence of diseases which are currently well controlled.[129] For example, cases of tuberculosis that are resistant to traditionally effective treatments remain a cause of great concern to health professionals. Every year, nearly half a million new cases of multidrug-resistant tuberculosis (MDR-TB) are estimated to occur worldwide.[130] China and India have the highest rate of multidrug-resistant TB.[131] The World Health Organization (WHO) reports that approximately 50 million people worldwide are infected with MDR TB, with 79 percent of those cases resistant to three or more antibiotics. In 2005, 124 cases of MDR TB were reported in the United States. Extensively drug-resistant tuberculosis (XDR TB) was identified in Africa in 2006, and subsequently discovered to exist in 49 countries, including the United States. There are about 40,000 new cases of XDR-TB per year, the WHO estimates.[132]
In the past 20 years, common bacteria including Staphylococcus aureus, Serratia marcescens and Enterococcus, have developed resistance to various antibiotics such as vancomycin, as well as whole classes of antibiotics, such as the aminoglycosides and cephalosporins. Antibiotic-resistant organisms have become an important cause of healthcare-associated (nosocomial) infections (HAI). In addition, infections caused by community-acquired strains of methicillin-resistant Staphylococcus aureus (MRSA) in otherwise healthy individuals have become more frequent in recent years.
Viral hemorrhagic fevers[edit]
Viral hemorrhagic fevers such as Ebola virus disease, Lassa fever, Rift Valley fever, Marburg virus disease and Bolivian hemorrhagic fever are highly contagious and deadly diseases, with the theoretical potential to become pandemics.[133] Their ability to spread efficiently enough to cause a pandemic is limited, however, as transmission of these viruses requires close contact with the infected vector, and the vector has only a short time before death or serious illness. Furthermore, the short time between a vector becoming infectious and the onset of symptoms allows medical professionals to quickly quarantine vectors, and prevent them from carrying the pathogen elsewhere. Genetic mutations could occur, which could elevate their potential for causing widespread harm; thus close observation by contagious disease specialists is merited.[citation needed]
Coronaviruses[edit]
Coronaviruses (CoV) are a large family of viruses that cause illness ranging from the common cold to more severe diseases such as Middle East Respiratory Syndrome (MERS-CoV) and Severe Acute Respiratory Syndrome (SARS-CoV). A new strain of coronavirus (SARS-CoV-2) causes Coronavirus disease 2019, or COVID-19.[134]
COVID-19 was declared a pandemic by the WHO on 11 March 2020.
Some coronaviruses are zoonotic, meaning they are transmitted between animals and people. Detailed investigations found that SARS-CoV was transmitted from civet cats to humans, and MERS-CoV from dromedary camels to humans. Several known coronaviruses are circulating in animals that have not yet infected humans. Common signs of infection include respiratory symptoms, fever, cough, shortness of breath, and breathing difficulties. In more severe cases, infection can cause pneumonia, severe acute respiratory syndrome, kidney failure and even death. Standard recommendations to prevent the spread of infection include regular hand washing, covering mouth and nose when coughing and sneezing, thoroughly cooking meat and eggs, and avoiding close contact with anyone showing symptoms of respiratory illness such as coughing and sneezing. The recommended distance from other people is 6 feet, a practice more commonly called social distancing.
Severe acute respiratory syndrome[edit]
In 2003 the Italian physician Carlo Urbani (1956–2003) was the first to identify severe acute respiratory syndrome (SARS) as a new and dangerously contagious disease, although he became infected and died. It is caused by a coronavirus dubbed SARS-CoV. Rapid action by national and international health authorities such as the World Health Organization helped to slow transmission and eventually broke the chain of transmission, which ended the localized epidemics before they could become a pandemic. However, the disease has not been eradicated and could re-emerge. This warrants monitoring and reporting of suspicious cases of atypical pneumonia.[135]
Influenza[edit]
Main article: Influenza pandemic
President Barack Obama is briefed in the Situation Room about the 2009 flu pandemic, which killed as many as 17,000 Americans.[136]
Wild aquatic birds are the natural hosts for a range of influenza A viruses. Occasionally, viruses are transmitted from these species to other species, and may then cause outbreaks in domestic poultry or, rarely, in humans.[137][138]
H5N1 (Avian flu)[edit]
Main article: Influenza A virus subtype H5N1
In February 2004, avian influenza virus was detected in birds in Vietnam, increasing fears of the emergence of new variant strains. It is feared that if the avian influenza virus combines with a human influenza virus (in a bird or a human), the new subtype created could be both highly contagious and highly lethal in humans. Such a subtype could cause a global influenza pandemic, similar to the Spanish flu or the lower mortality pandemics such as the Asian Flu and the Hong Kong Flu.
From October 2004 to February 2005, some 3,700 test kits of the 1957 Asian Flu virus were accidentally spread around the world from a lab in the U.S.[139]
In May 2005, scientists urgently called upon nations to prepare for a global influenza pandemic that could strike as much as 20% of the world's population.[140]
In October 2005, cases of the avian flu (the deadly strain H5N1) were identified in Turkey. EU Health Commissioner Markos Kyprianou said: "We have received now confirmation that the virus found in Turkey is an avian flu H5N1 virus. There is a direct relationship with viruses found in Russia, Mongolia and China." Cases of bird flu were also identified shortly thereafter in Romania, and then Greece. Possible cases of the virus have also been found in Croatia, Bulgaria and the United Kingdom.[141]
By November 2007, numerous confirmed cases of the H5N1 strain had been identified across Europe.[142] However, by the end of October, only 59 people had died as a result of H5N1, which was atypical of previous influenza pandemics.
Avian flu cannot be categorized as a "pandemic" because the virus cannot yet cause sustained and efficient human-to-human transmission. Cases so far are recognized to have been transmitted from bird to human, but as of December 2006 there had been few (if any) cases of proven human-to-human transmission.[143] Regular influenza viruses establish infection by attaching to receptors in the throat and lungs, but the avian influenza virus can attach only to receptors located deep in the lungs of humans, requiring close, prolonged contact with infected patients, and thus limiting person-to-person transmission.
Zika virus[edit]
Main articles: 2015–16 Zika virus epidemic, Zika virus, and Zika fever
An outbreak of Zika virus began in 2015 and strongly intensified throughout the start of 2016, with more than 1.5 million cases across more than a dozen countries in the Americas. The World Health Organization warned that Zika had the potential to become an explosive global pandemic if the outbreak was not controlled.[144]
Economic consequences[edit]
In 2016, the Commission on a Global Health Risk Framework for the Future estimated that pandemic disease events would cost the global economy over $6 trillion in the 21st century—over $60 billion per year.[145] The same report recommended spending $4.5 billion annually on global prevention and response capabilities to reduce the threat posed by pandemic events.
Biological warfare[edit]
Further information: Biological warfare
In 1346, according to secondhand and uncorroborated accounts by Mussi, the bodies of Mongol warriors who had died of plague were thrown over the walls of the besieged Crimean city of Kaffa (now Theodosia). After a protracted siege, during which the Mongol army under Jani Beg was suffering the disease, they catapulted the infected corpses over the city walls to infect the inhabitants. It has been speculated that this operation may have been responsible for the arrival of the Black Death in Europe. However, historians believe it would have taken far too long for the bodies to become contagious.[146]
The Native American population was devastated after contact with the Old World by introduction of many fatal diseases.[147][148][149] In a well documented case of germ warfare involving British commander Jeffery Amherst and Swiss-British officer Colonel Henry Bouquet, their correspondence included a proposal and agreement to give smallpox-infected blankets to Indians in order to "Extirpate this Execrable Race". During the siege of Fort Pitt late in the French and Indian War, as recorded in his journal by sundries trader and militia Captain, William Trent, on 24 June 1763, dignitaries from the Delaware tribe met with Fort Pitt officials, warned them of "great numbers of Indians" coming to attack the fort, and pleaded with them to leave the fort while there was still time. The commander of the fort refused to abandon the fort. Instead, the British gave as gifts two blankets, one silk handkerchief and one linen from the smallpox hospital to two Delaware Indian dignitaries.[150] The dignitaries were met again later and they seemingly hadn't contracted smallpox.[151] A relatively small outbreak of smallpox had begun spreading earlier that spring, with a hundred dying from it among Native American tribes in the Ohio Valley and Great Lakes area through 1763 and 1764.[151] The effectiveness of the biological warfare itself remains unknown, and the method used is inefficient compared to respiratory transmission and these attempts to spread the disease are difficult to differentiate from epidemics occurring from previous contacts with colonists,[152] as smallpox outbreaks happened every dozen or so years.[153] However historian Francis Jennings believes that the attempt at biological warfare was "unquestionably effective at Fort Pitt".[154]
During the Sino-Japanese War (1937–1945), Unit 731 of the Imperial Japanese Army conducted human experimentation on thousands, mostly Chinese. In military campaigns, the Japanese army used biological weapons on Chinese soldiers and civilians. Plague fleas, infected clothing, and infected supplies encased in bombs were dropped on various targets. The resulting cholera, anthrax, and plague were estimated to have killed around 400,000 Chinese civilians.
Diseases considered for or known to be used as a weapon include anthrax, ebola, Marburg virus, plague, cholera, typhus, Rocky Mountain spotted fever, tularemia, brucellosis, Q fever, machupo, Coccidioides mycosis, Glanders, Melioidosis, Shigella, Psittacosis, Japanese B encephalitis, Rift Valley fever, yellow fever, and smallpox.[155]
Spores of weaponized anthrax were accidentally released from a military facility near the Soviet closed city of Sverdlovsk in 1979. The Sverdlovsk anthrax leak is sometimes called "biological Chernobyl".[155] In January 2009, an Al-Qaeda training camp in Algeria was reportedly wiped out by the plague, killing approximately 40 Islamic extremists. Some experts said the group was developing biological weapons,[156] however, a couple of days later the Algerian Health Ministry flatly denied this rumour stating "No case of plague of any type has been recorded in any region of Algeria since 2003".[157]
In popular culture[edit]
This section contains a list of miscellaneous information. Please relocate any relevant information into other sections or articles. (March 2020)
Pieter Bruegel's The Triumph of Death (c. 1562) reflects the social upheaval and terror that followed the plague that devastated medieval Europe.
Pandemics appear in multiple fiction works. A common use is in disaster films, where the protagonists must avoid the effects of the plague, for example zombies.[clarification needed]
Literature
The Decameron, a 14th-century writing by Italian author Giovanni Boccaccio, circa 1353
The Last Man, an 1826 novel by Mary Shelley
The Betrothed, an 1842 historical novel by Alessandro Manzoni describing the plague that struck Milan around 1630.
Pale Horse, Pale Rider, a 1939 short novel by Katherine Anne Porter
The Plague, a 1947 novel by Albert Camus
Earth Abides, a 1949 novel by George R. Stewart
I Am Legend, a 1954 science fiction/horror novel by American writer Richard Matheson
The Andromeda Strain, a 1969 science fiction novel by Michael Crichton
The Last Canadian, a 1974 novel by William C. Heine
The Black Death, a 1977 novel by Gwyneth Cravens describing an outbreak of the Pneumonic plague in New York[158]
The Stand, a 1978 novel by Stephen King
And the Band Played On, a 1987 non-fiction account by Randy Shilts about the emergence and discovery of the HIV / AIDS pandemic
Doomsday Book, a 1992 time-travel novel by Connie Willis
The Last Town on Earth, a 2006 novel by Thomas Mullen
World War Z, a 2006 novel by Max Brooks
Company of Liars (2008), by Karen Maitland
The Passage trilogy by Justin Cronin with The Passage (2010), The Twelve (2012), and The City of Mirrors (2016)
Station Eleven, a 2014 novel by Emily St. John Mandel
Film
The Seventh Seal (1957), set during the Black Death
The Last Man on Earth (1964), a horror/science fiction film based on the Richard Matheson novel I Am Legend
Andromeda Strain (1971), a U.S. science fiction film based on the 1969 science fiction novel by Michael Crichton.
The Omega Man (1971), an English science fiction film, based on the Richard Matheson novel I Am Legend
And the Band Played On (film) (1993), a HBO movie about the emergence of the HIV / AIDS pandemic; based on the 1987 non-fiction book by journalistRandy Shilts
The Stand (1994), based on the eponymous novel by Stephen King about a worldwide pandemic of biblical proportions
The Horseman on the Roof (Le Hussard sur le Toit) (1995), a French film dealing with an 1832 cholera outbreak
Twelve Monkeys (1995), set in a future world devastated by a man-made virus
Outbreak (1995), fiction film focusing on an outbreak of an Ebola-like virus in Zaire and later in a small town in California.
Smallpox 2002 (2002), a fictional BBC docudrama
28 Days Later (2002), a fictional horror film following the outbreak of an infectious 'Rage' virus that destroys all of mainland Britain
Yesterday (2004), a movie about the social aspects of the AIDS crisis in Africa.
End Day (2005), a fictional BBC docudrama
I Am Legend (2007), a post-apocalyptic action thriller film film starring Will Smith based on the Richard Matheson novel I Am Legend
28 Weeks Later (2007), the sequel film to 28 Days Later, ending with the evident spread of infection to mainland Europe
The Happening (2008), a fictional suspense film about an epidemic caused by an unknown neurotoxin that induces human suicides to reduce population and restore ecological balance
Doomsday (2008), in which Scotland is quarantined following an epidemic
Black Death (2010) action horror film set during the time of the first outbreak of bubonic plague in England
After Armageddon (2010), fictional History Channel docudrama
Contagion (2011), American thriller centering on the threat posed by a deadly disease and an international team of doctors contracted by the CDC to deal with the outbreak
How to Survive a Plague (2012), a documentary film about the early years of the AIDS epidemic
World War Z (2013) American apocalyptic action horror film based on the novel by Max Brooks
The Normal Heart (2014), film depicts the rise of the HIV-AIDS crisis in New York City between 1981 and 1984
Television
Spanish Flu: The Forgotten Fallen (2009), a television drama
Helix (2014–2015), a television series that depicts a team of scientists from the Centers for Disease Control and Prevention (CDC) who are tasked to prevent pandemics from occurring.
The Last Man on Earth (2015–2018), a television series about a group of survivors after a pandemic has wiped out most life (humans and animals) on Earth
12 Monkeys (2015–2018), a television series that depicts James Cole, a time traveler, who travels from the year 2043 to the present day to stop the release of a deadly virus.
Survivors (1975–1977), classic BBC series created by Terry Nation. The series follows a group of people as they come to terms with the aftermath of a world pandemic.
Survivors (2008), BBC series, loosely based on the Terry Nation book which came after the series, instead of a retelling of the original TV series.
The Last Train 1999 written by Matthew Graham
World Without End (2012), chronicles the experiences of the medieval English town of Kingsbridge during the outbreak of the Black Death, based on Ken Follett's 2007 novel of the same name.
The Hot Zone (2019), a television series based on the 1994 non-fiction book of the same name by Richard Preston.
Pandemic: How to Prevent an Outbreak (2020), Netflix's docuseries
The Walking Dead (2010–), a virus appears that kills people and then revives them by turning them into zombies. An Atlanta group will try to survive in this new, post-apocalyptic world
Games
Resident Evil series (1996-2020), video game series focusing on T-virus pandemic and eventual zombie apocalypse as part of a bioterrorism act. The video games later evolved to be focusing on parasites and bioweapons.
Deus Ex, A World Wide Plague known as grey death infects the world created by Majestic 12 to bring about population reduction and New World order.
Pandemic (2008), a cooperative board game in which the players have to discover the cures for four diseases that break out at the same time.
Plague Inc. (2012), a smartphone game from Ndemic Creations, where the goal is to kill off the human race with a plague.
The Last of Us (2013), a post-apocalyptic survival game centred around an outbreak of a Cordyceps-like fungal infection.
Tom Clancy's The Division (2015) A video game about a bioterrorist attack that has devastated the United States and thrown New York into anarchy.
See also[edit]
Pandemic portal
iconViruses portal
List of epidemics
Biological hazard
Bushmeat
Compartmental models in epidemiology
Crowdmapping
Disease X
European Centre for Disease Prevention and Control (ECDC)
Mathematical modelling of infectious disease
Medieval demography
Mortality from infectious diseases
Pandemic severity index
Public health emergency of international concern
Super-spreader
Syndemic
Tropical disease
Timeline of global health
WHO pandemic phases
Notes[edit]
^ For clarification, WHO does not use the old system of six phases—ranging from phase 1 (no reports of animal influenza causing human infections) to phase 6 (a pandemic)—that some people may be familiar with from H1N1 in 2009.
References[edit]
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The Indian Flying Fox, also known as the greater Indian Fruit Bat, is a species of megabat in the Pteropodidae family. It is nocturnal and feeds mainly on ripe fruits, such as mangoes and bananas, and nectar. At dusk, these bats forage for ripe fruit. While ingesting fruit, these bats expel waste that pollinates and disperse seeds. They are mammals and have live births. Their offspring have no specific name besides 'young'. They have one to two young. This bat is gregarious and roosts in colonies which can number up to 1,000 individuals, during the day. Like other fruit bats, the Indian flying fox has been found to act as a natural reservoir for a number of diseases including ebola, rabies, and coronaviruses. These can prove fatal to humans and domestic animals. Clicked in the backyard where they are often seen hanging from the branches of trees looking like a fox in a cloak hanging upside down. They have pretty big wingspans and are an eerie sight when seen from close and in flight.
During the COVID-19 pandemic, face masks, such as surgical masks and cloth masks, have been employed as a public and personal health control measure against the spread of SARS-CoV-2. In both community and healthcare settings, their use is intended as source control to limit transmission of the virus and personal protection to prevent infection. Their function for source control is emphasized in community settings.
The use of face masks (or coverings in some cases) has been recommended by American immunologist and NIAID director Anthony Fauci to reduce the risk of contagion. In the COVID-19 pandemic, governments recommend the use of face masks with a main purpose for the general population: to avoid the contagion from infected people to others. Masks with exhalation valves are not recommended, because they expel the breath of the wearer outwards, and an infected wearer would transmit the viruses through the valve. A second purpose of the face masks is to protect to each wearer from environments that can be infected, which can be achieved by many models of masks..Between the different types of face masks that have been recommended throughout the COVID-19 pandemic, with higher or lower effectivity, it is possible to include: cloth face masks surgical masks (medical masks) uncertified face-covering dust masks certified face-covering masks, considered respirators, with certifications such as N95 and N99, and FFP filtering respirators with certifications such as N95 and N99, and FFP other respirators, including elastomeric respirators, some of which may also be considered filtering masks There are some other types of personal protective equipment (PPE), as face shields and medical goggles, that are sometimes used in conjunction with face masks but are not recommended as a replacement. Other kinds of PPE include gloves, aprons, gowns, shoe covers and hair covers. A cloth face mask is worn over the mouth and nose and made of commonly available textiles. Masks vary widely in effectiveness, depending on material, fit and seal, number of layers, and other factors. Although they are usually less effective than medical-grade masks,[citation needed] some health authorities recommend their use by the general public when medical-grade masks are in short supply, as a low-cost and reusable option. Unlike disposable masks, there are no required standards for cloth masks. One study gives evidence that an improvised mask was better than nothing, but not as good as soft electret-filter surgical mask, for protecting healthcare workers while simulating treatment of an artificially infected patient. Research on commonly available fabrics used in cloth masks found that cloth masks can provide significant protection against the transmission of particles in the aerosol size range, with enhanced performance across the nano- and micronscale when masks utilize both mechanical and electrostatic-based filtration, but that leakage due to improper fit can degrade performance.[10] A review of available research published in January 2021 concludes that cloth masks are not considered adequate to protect healthcare practitioners in a clinical setting. Another study had volunteers wear masks they made themselves, from cotton T-shirts and following the pattern of a standard tie behind the head surgical mask, and found the number of microscopic particles that leaked to the inside of the homemade masks were twice that of commercial masks. Wearing homemade masks also leaked a median average of three times as many microorganisms as commercial masks. But another study found that masks made of at least two layers T-shirt fabric could be as protective against virus droplets as medical masks, and as breathable. A woman sews a multi-layered woven cloth face mask on a sewing machine. Many people made cloth face masks at home during the pandemic. World Health Organization infographic on how to wear a non-medical fabric mask safely. A peer-reviewed summary of published literature on the filtration properties of cloth and cloth masks suggested two to four layers of plain-weave cotton or flannel, of at least 100 threads per inch. There is a necessary trade-off: increasing the number of layers increases the filtration of the material but decreases breathability. Decreased breathability makes it harder to wear a mask and also increases the amount of leak around the edge of the mask. A plain-language summary of this work,[16] along with a hand-sewn design, suggestions on materials and layering, and how to put on, take off, and clean cloth masks are available. As of May 2020, there was no research on decontaminating and reusing cloth masks. The CDC recommends removing a mask by handling only the ear loops or ties, placing it directly in a washing machine, and immediately washing hands in soap and water for at least twenty seconds. Cold water is considered as effective as warm water for decontamination. The CDC also recommends washing hands before putting on the mask, and again immediately after touching it. There is no information on reusing an interlayer filter. Disposing of filters after a single use may be desirable. A narrative review of the literature on filtration properties of cloth and other household materials did not find support for the idea of using a filter. A layer of cloth, if tolerated, was suggested instead, or a PM2.5 filter, as a third layer. A surgical mask is a loose-fitting, disposable mask that creates a physical barrier separating the mouth and nose of the wearer from potential contaminants in the immediate environment. If worn properly, a surgical mask is meant to help block large-particle droplets, splashes, sprays, or splatter that may contain viruses and bacteria, keeping them from reaching the wearer's mouth and nose. Surgical masks may also help reduce exposure of others to the wearer's saliva and respiratory secretions. Certified medical masks are made of non-woven material and they are mostly multi-layer. Filters may be made of microfibers with an electrostatic charge; that is, the fibers are electrets. An electret filter increases the chances that smaller particles will veer and hit a fiber, rather than going straight through (electrostatic capture). While there is some development work on making electret filtering materials that can be washed and reused, current commercially produced electret filters are ruined by many forms of disinfection, including washing with soap and water or alcohol, which destroys the electric charge.[30] During the COVID-19 pandemic, public health authorities issued guidelines on how to save, disinfect and reuse electret-filter masks without damaging the filtration efficiency. Standard disposable surgical masks are not designed to be washed. Surgical masks may be labeled as surgical, isolation, dental, or medical procedure masks. The material surgical masks are made from is much poorer at filtering very small particles (in range a tenth of a micrometre to a micrometre across) than that of filtering respirators (for example N95, FFP2) and the fit is much poorer. Surgical masks are made of a non-woven fabric created using a melt blowing process. Random control studies of respiratory infections like influenza find little difference in protection between surgical masks and respirators (such as N95 or FFP masks). However, the filtering performance of correctly worn N95/FFP2 type filtering respirators is clearly superior to surgical and to cloth masks and for influenza, work by the UK Health and Safety executive found that live virus penetrated all surgical masks tested but properly fitted respirators reduced the viral dose by a factor of at least a hundred. Tsai Ing-wen, President of Taiwan, wearing a surgical mask Surgical masks made to different standards in different parts of the world have different ranges of particles which they filter. For example, the People's Republic of China regulates two types of such masks: single-use medical masks (Chinese standard YY/T 0969) and surgical masks (YY 0469). The latter ones are required to filter bacteria-sized particles (BFE ≥ 95%) and some virus-sized particles (PFE ≥ 30%), while the former ones are required to only filter bacteria-sized particles. The effectiveness of surgical masks in limiting particle transmission is a function of material and fit. Since the start of the pandemic, scientists have evaluated various modifications to ear loop surgical masks aimed at improving mask efficacy by reducing or eliminating gaps between the mask and face. The CDC evaluated and recommends two such modifications to ear loop masks to reduce transmission of SARS-CoV-2. Under normal use, the CDC found that a surgical mask worn by a coughing individual blocked 41.3% of simulated cough aerosols (0.1–7.0 μm particle size) from reaching a second individual six feet away. However, by applying a knot and tuck technique,[a] 62.9% of particles were blocked. When the surgical mask was covered with a larger cloth mask, 82% of particles were blocked. When both the source and recipient wore masks, 84% of particles were blocked. The number increased to more than 95% when both parties either wore double masks (surgical mask with larger cloth mask) or used the knot and tuck technique. Il Another type of modifications was aimed to improve the comfort of the wearers. Early on in the pandemic, healthcare workers were required to continue wearing surgical masks for 12 or more hours a day. This caused the ear loops of the masks to chafe the back of their ears. Ear savers, plastic straps and hooks that go around wearer's heads, were invented to move the ear loops away from the wearer's ears. They could be made on demand by using 3D printing process. An N95 mask is a particulate-filtering facepiece respirator that meets the N95 air filtration rating of the US National Institute for Occupational Safety and Health, meaning it filters at least 95 percent of airborne particles, while not resistant to oil like the P95. It is the most common particulate-filtering facepiece respirator. It is an example of a mechanical filter respirator, which provides protection against particulates, but not gases or vapors. Like the middle layer of surgical masks, the N95 mask is made of four layers[ of melt-blown nonwoven polypropylene fabric. The corresponding face mask used in the European Union is the FFP2 respirator. Hard electret-filter masks like N95 and FFP masks must fit the face to provide full protection. Untrained users often get a reasonable fit, but fewer than one in four gets a perfect fit. Fit testing is thus standard. A line of petroleum jelly on the edge of the mask. has been shown to reduce edge leakage in lab tests using mannequins that simulate breathing. Some N95 series respirators, especially those intended for industrial use, have an exhalation valve to improve comfort, making exhalation easier and reducing leakage on exhalation and steaming-up of glasses. But those respirators are not reliable for the control of infected people (source control) in respiratory diseases such as COVID-19, because infected users (asymptomatic or not) would transmit the virus to others through the valve. During the COVID-19 pandemic, there were shortages of filtering facepiece respirators, and they had to be used for extended periods, and/or disinfected and reused. At the time, public health authorities issued guidelines on how to save, disinfect and reuse masks, as some disinfection methods damaged their filtration efficiency. Some hospitals stockpiled used masks as a precaution, and some had to sanitize and reuse masks. The US Centers for Disease Control and Prevention (CDC) does not recommend the use of face shields as a substitute for masks to help slow the spread of COVID-19.[54] In a study by Lindsley et al. (7 January 2021) funded by the National Institute for Occupational Safety and Health, part of the CDC, face shields were found to block very few cough aerosols in contrast to face coverings – such as cloth masks, procedure masks, and N95 respirators – indicating that face shields are not effective as source control devices for small respiratory aerosols and that face coverings are more effective than face shields as source control devices to reduce the community transmission of SARS-CoV-2. In a scoping review, Godoy et al. (5 May 2020) said face shields are used for barrier protection against splash and splatter contamination, but should not be used as primary protection against respiratory disease transmission due to the lack of a peripheral seal rather than as an adjunct to other facial protection. They remarked that face shields have been used like this alongside medical-grade masks during the COVID-19 pandemic. They cited a cough simulation study by Lindsley et al. (2014) in which face shields were shown to reduce the risk of inhalation exposure up to 95% immediately following aerosol production, but the protection was decreased with smaller aerosol particles and persistent airborne particles around the sides. A systematic review of observational studies on the transmission of coronaviruses, funded by the World Health Organization found that eye protection including face shields was associated with less infection (adjusted odds ratio 0.22; 95% confidence interval 0·12 to 0·39), but the evidence was rated as low certainty. Elastomeric respirators are reusable personal protective equipment comprising a tight-fitting half-facepiece or full-facepiece respirator with exchangeable filters such as cartridge filters. They provide an alternative respiratory protection option to filtering facepiece respirators such as N95 masks for healthcare workers during times of short supply caused by the pandemic, as they can be reused over an extended period in healthcare settings. However, elastomeric respirators have a vent to exhalate the air outwards and unfiltered, so the wearer must be attentive that he or she is not infected with SARS-CoV-2, to prevent a possible transmission of the virus to others through the vent. For the COVID-19 response when supplies are short, the US CDC says contingency and crisis strategies should be followed: Each elastomeric respirator is issued for the exclusive use of an individual healthcare provider, but must be cleaned and disinfected as often as necessary to remain unsoiled and sanitary. If there is no other option than to share a respirator between healthcare providers, the respirator must be cleaned and disinfected before it is worn by a different individual. Filters (except for unprotected disc types) may be used for an extended period, but the filter housing of cartridge types must be disinfected after each patient interaction. A powered air-purifying respirator (PAPR) is a personal protective equipment in which a device with a filter and fan creates a highly filtered airflow towards the headpiece and a positive outflow of air from the headpiece. There is an increased risk for healthcare workers to become exposed to SARS-CoV-2 when they conduct aerosol-generating procedures on COVID-19 patients, which is why it is argued that such situations may require enhanced personal protective equipment (i.e., higher than N95) such as PAPRs for healthcare workers. In a systematic review, Licina, Silvers, and Stuart (8 August 2020) said field studies indicate that there was equivalent rates of infection between healthcare workers, who performed airway procedures on critical COVID-19 patients, utilizing PAPRs or other appropriate respiratory equipment (such as N95 or FFP2), but remarked that there is a need to further collect field data about optimal respiratory protection during highly virulent pandemics. Some masks include an exhalation valve to expel the breath outwards, but that current of air is not filtered. Certification (as N95 or FFP2) is about the mask itself and does not warrant any safety about the air that is exhaled. Putting tape over the exhalation valve can make a mask or respirator as effective as one without a valve. Scientists have visualized droplet dispersal for masks with exhalation valves and face shields, and concluded that they can be ineffective against COVID-19 spread (e.g., after a cough) and recommended alternatives. The use of face masks or coverings by the general public has been recommended by health officials to minimize the risk of transmissions, with authorities either requiring their use in certain settings, such as on public transport and in shops, or universally in public. Health officials have advised that medical-grade face masks, such as respirators, should be prioritized for use by healthcare workers in view of critical shortages, so they generally first and foremost recommend cloth masks for the general public. The recommendations have changed as the body of scientific knowledge evolved. According to #Masks4All, about 95% of the world population lives in countries where the government and leading disease experts recommend or require the use of masks in public places to limit the spread of COVID-19. Early in 2020, the WHO had only recommended medical masks for people with suspected infection and respiratory symptoms, their caregivers and those sharing living space, and healthcare workers.[71][72][73] In April 2020, the WHO acknowledged that wearing a medical mask can limit the spread of certain respiratory viral diseases including COVID-19, but claimed that medical masks would create a false sense of security and neglect of other necessary measures, such as hand hygiene. The early WHO advice on limited mask usage was scrutinized for several reasons. First, experts and researchers pointed out the asymptomatic transmission of the virus. Second, according to Marteau et al. (27 July 2020), available evidence does not support the notion that masking adversely affects hand hygiene: Dame Theresa Marteau, one of the researchers, remarked that "The concept of risk compensation, rather than risk compensation itself, seems the greater threat to public health through delaying potentially effective interventions that can help prevent the spread of disease." The WHO revised its mask guidance in June 2020, with its officials acknowledging that studies indicated asymptomatic or pre-symptomatic spread.[81] The updated advice recommended that the general public should wear non-medical fabric masks where there is known or suspected widespread transmission and where physical distancing is not possible, and that vulnerable people (60 and over, or with underlying health risks) and people with any symptoms suggestive of COVID-19 as well as caregivers and healthcare workers should wear surgical or procedure masks.[68] They stated that the purpose of mask usage is to prevent the wearer transmitting the virus to others (source control) and to offer protection to healthy wearers against infection (prevention). The WHO advises that non-medical fabric masks should comprise a minimum of three layers, suggesting an inner layer made of absorbent material (such as cotton), a middle layer made of non-woven material (such as polypropylene) which may enhance filtration or retain droplets, and an outer layer made of non-absorbent material (such as polyester or its blends) which may limit external contamination from penetration. On 21 August 2020, the WHO and UNICEF released an annex guidance for children.[83] For children five and younger, they advise that masks should not be required in consideration to a child's developmental milestones, compliance challenges, and autonomy required to use a mask properly, but recognized that the evidence supporting their cut-off age is limited and countries may hold a different and lower age of cut-off. For children 6–11, they advise that mask usage should be decided in consideration of several factors including the intensity of local viral transmission, (the latest evidence about) the risk of infection for the age group, the social and cultural environment (which influences social interactions in communities and populations), the capacity to comply with appropriate mask usage, the availability of appropriate adult supervision, and the potential impact on learning and psychosocial development, as well as additional factors involving specific settings or circumstances (such as disabilities, underlying diseases, elderly people, sport activities, and schools). For children 12 and older, they advise that masks should be worn under the same conditions for adults in accordance to WHO guidance or national guidelines. Regarding the use of non-medical fabric masks in the general population, the WHO has stated that high-quality evidence for its widespread use is limited, but advises governments to encourage its use as physical distancing may not be possible in some settings, there is some evidence for asymptomatic transmission, and masks could be helpful to provide a barrier to limit the spread of potentially infectious droplets.
en.wikipedia.org/wiki/Face_masks_during_the_COVID-19_pand...
Coronavirus disease 2019 (COVID-19) is an infectious disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).[8] The disease was first identified in December 2019 in Wuhan, the capital of China's Hubei province, and has since spread globally, resulting in the ongoing 2019–20 coronavirus pandemic.[9][10] As of 26 April 2020, more than 2.89 million cases have been reported across 185 countries and territories, resulting in more than 203,000 deaths. More than 822,000 people have recovered.[7]
Common symptoms include fever, cough, fatigue, shortness of breath and loss of smell.[5][11][12] While the majority of cases result in mild symptoms, some progress to viral pneumonia, multi-organ failure, or cytokine storm.[13][9][14] More concerning symptoms include difficulty breathing, persistent chest pain, confusion, difficulty waking, and bluish skin.[5] The time from exposure to onset of symptoms is typically around five days but may range from two to fourteen days.[5][15]
The virus is primarily spread between people during close contact,[a] often via small droplets produced by coughing,[b] sneezing, or talking.[6][16][18] The droplets usually fall to the ground or onto surfaces rather than remaining in the air over long distances.[6][19][20] People may also become infected by touching a contaminated surface and then touching their face.[6][16] In experimental settings, the virus may survive on surfaces for up to 72 hours.[21][22][23] It is most contagious during the first three days after the onset of symptoms, although spread may be possible before symptoms appear and in later stages of the disease.[24] The standard method of diagnosis is by real-time reverse transcription polymerase chain reaction (rRT-PCR) from a nasopharyngeal swab.[25] Chest CT imaging may also be helpful for diagnosis in individuals where there is a high suspicion of infection based on symptoms and risk factors; however, guidelines do not recommend using it for routine screening.[26][27]
Recommended measures to prevent infection include frequent hand washing, maintaining physical distance from others (especially from those with symptoms), covering coughs, and keeping unwashed hands away from the face.[28][29] In addition, the use of a face covering is recommended for those who suspect they have the virus and their caregivers.[30][31] Recommendations for face covering use by the general public vary, with some authorities recommending against their use, some recommending their use, and others requiring their use.[32][31][33] Currently, there is not enough evidence for or against the use of masks (medical or other) in healthy individuals in the wider community.[6] Also masks purchased by the public may impact availability for health care providers.
Currently, there is no vaccine or specific antiviral treatment for COVID-19.[6] Management involves the treatment of symptoms, supportive care, isolation, and experimental measures.[34] The World Health Organization (WHO) declared the 2019–20 coronavirus outbreak a Public Health Emergency of International Concern (PHEIC)[35][36] on 30 January 2020 and a pandemic on 11 March 2020.[10] Local transmission of the disease has occurred in most countries across all six WHO regions.[37]
File:En.Wikipedia-VideoWiki-Coronavirus disease 2019.webm
Video summary (script)
Contents
1Signs and symptoms
2Cause
2.1Transmission
2.2Virology
3Pathophysiology
3.1Immunopathology
4Diagnosis
4.1Pathology
5Prevention
6Management
6.1Medications
6.2Protective equipment
6.3Mechanical ventilation
6.4Acute respiratory distress syndrome
6.5Experimental treatment
6.6Information technology
6.7Psychological support
7Prognosis
7.1Reinfection
8History
9Epidemiology
9.1Infection fatality rate
9.2Sex differences
10Society and culture
10.1Name
10.2Misinformation
10.3Protests
11Other animals
12Research
12.1Vaccine
12.2Medications
12.3Anti-cytokine storm
12.4Passive antibodies
13See also
14Notes
15References
16External links
16.1Health agencies
16.2Directories
16.3Medical journals
Signs and symptoms
Symptom[4]Range
Fever83–99%
Cough59–82%
Loss of Appetite40–84%
Fatigue44–70%
Shortness of breath31–40%
Coughing up sputum28–33%
Loss of smell15[38] to 30%[12][39]
Muscle aches and pains11–35%
Fever is the most common symptom, although some older people and those with other health problems experience fever later in the disease.[4][40] In one study, 44% of people had fever when they presented to the hospital, while 89% went on to develop fever at some point during their hospitalization.[4][41]
Other common symptoms include cough, loss of appetite, fatigue, shortness of breath, sputum production, and muscle and joint pains.[4][5][42][43] Symptoms such as nausea, vomiting and diarrhoea have been observed in varying percentages.[44][45][46] Less common symptoms include sneezing, runny nose, or sore throat.[47]
More serious symptoms include difficulty breathing, persistent chest pain or pressure, confusion, difficulty waking, and bluish face or lips. Immediate medical attention is advised if these symptoms are present.[5][48]
In some, the disease may progress to pneumonia, multi-organ failure, and death.[9][14] In those who develop severe symptoms, time from symptom onset to needing mechanical ventilation is typically eight days.[4] Some cases in China initially presented with only chest tightness and palpitations.[49]
Loss of smell was identified as a common symptom of COVID‑19 in March 2020,[12][39] although perhaps not as common as initially reported.[38] A decreased sense of smell and/or disturbances in taste have also been reported.[50] Estimates for loss of smell range from 15%[38] to 30%.[12][39]
As is common with infections, there is a delay between the moment a person is first infected and the time he or she develops symptoms. This is called the incubation period. The incubation period for COVID‑19 is typically five to six days but may range from two to 14 days,[51][52] although 97.5% of people who develop symptoms will do so within 11.5 days of infection.[53]
A minority of cases do not develop noticeable symptoms at any point in time.[54][55] These asymptomatic carriers tend not to get tested, and their role in transmission is not yet fully known.[56][57] However, preliminary evidence suggests they may contribute to the spread of the disease.[58][59] In March 2020, the Korea Centers for Disease Control and Prevention (KCDC) reported that 20% of confirmed cases remained asymptomatic during their hospital stay.[59][60]
A number of neurological symptoms has been reported including seizures, stroke, encephalitis and Guillain-Barre syndrome.[61] Cardiovascular related complications may include heart failure, irregular electrical activity, blood clots, and heart inflammation.[62]
Cause
See also: Severe acute respiratory syndrome coronavirus 2
Transmission
Cough/sneeze droplets visualised in dark background using Tyndall scattering
Respiratory droplets produced when a man is sneezing visualised using Tyndall scattering
File:COVID19 in numbers- R0, the case fatality rate and why we need to flatten the curve.webm
A video discussing the basic reproduction number and case fatality rate in the context of the pandemic
Some details about how the disease is spread are still being determined.[16][18] The WHO and the U.S. Centers for Disease Control and Prevention (CDC) say it is primarily spread during close contact and by small droplets produced when people cough, sneeze or talk;[6][16] with close contact being within approximately 1–2 m (3–7 ft).[6][63] Both sputum and saliva can carry large viral loads.[64] Loud talking releases more droplets than normal talking.[65] A study in Singapore found that an uncovered cough can lead to droplets travelling up to 4.5 metres (15 feet).[66] An article published in March 2020 argued that advice on droplet distance might be based on 1930s research which ignored the effects of warm moist exhaled air surrounding the droplets and that an uncovered cough or sneeze can travel up to 8.2 metres (27 feet).[17]
Respiratory droplets may also be produced while breathing out, including when talking. Though the virus is not generally airborne,[6][67] the National Academy of Sciences has suggested that bioaerosol transmission may be possible.[68] In one study cited, air collectors positioned in the hallway outside of people's rooms yielded samples positive for viral RNA but finding infectious virus has proven elusive.[68] The droplets can land in the mouths or noses of people who are nearby or possibly be inhaled into the lungs.[16] Some medical procedures such as intubation and cardiopulmonary resuscitation (CPR) may cause respiratory secretions to be aerosolised and thus result in an airborne spread.[67] Initial studies suggested a doubling time of the number of infected persons of 6–7 days and a basic reproduction number (R0 ) of 2.2–2.7, but a study published on April 7, 2020, calculated a much higher median R0 value of 5.7 in Wuhan.[69]
It may also spread when one touches a contaminated surface, known as fomite transmission, and then touches one's eyes, nose or mouth.[6] While there are concerns it may spread via faeces, this risk is believed to be low.[6][16]
The virus is most contagious when people are symptomatic; though spread is may be possible before symptoms emerge and from those who never develop symptoms.[6][70] A portion of individuals with coronavirus lack symptoms.[71] The European Centre for Disease Prevention and Control (ECDC) says while it is not entirely clear how easily the disease spreads, one person generally infects two or three others.[18]
The virus survives for hours to days on surfaces.[6][18] Specifically, the virus was found to be detectable for one day on cardboard, for up to three days on plastic (polypropylene) and stainless steel (AISI 304), and for up to four hours on 99% copper.[21][23] This, however, varies depending on the humidity and temperature.[72][73] Surfaces may be decontaminated with many solutions (with one minute of exposure to the product achieving a 4 or more log reduction (99.99% reduction)), including 78–95% ethanol (alcohol used in spirits), 70–100% 2-propanol (isopropyl alcohol), the combination of 45% 2-propanol with 30% 1-propanol, 0.21% sodium hypochlorite (bleach), 0.5% hydrogen peroxide, or 0.23–7.5% povidone-iodine. Soap and detergent are also effective if correctly used; soap products degrade the virus' fatty protective layer, deactivating it, as well as freeing them from the skin and other surfaces.[74] Other solutions, such as benzalkonium chloride and chlorhexidine gluconate (a surgical disinfectant), are less effective.[75]
In a Hong Kong study, saliva samples were taken a median of two days after the start of hospitalization. In five of six patients, the first sample showed the highest viral load, and the sixth patient showed the highest viral load on the second day tested.[64]
Virology
Main article: Severe acute respiratory syndrome coronavirus 2
Illustration of SARSr-CoV virion
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a novel severe acute respiratory syndrome coronavirus, first isolated from three people with pneumonia connected to the cluster of acute respiratory illness cases in Wuhan.[76] All features of the novel SARS-CoV-2 virus occur in related coronaviruses in nature.[77] Outside the human body, the virus is killed by household soap, which bursts its protective bubble.[26]
SARS-CoV-2 is closely related to the original SARS-CoV.[78] It is thought to have a zoonotic origin. Genetic analysis has revealed that the coronavirus genetically clusters with the genus Betacoronavirus, in subgenus Sarbecovirus (lineage B) together with two bat-derived strains. It is 96% identical at the whole genome level to other bat coronavirus samples (BatCov RaTG13).[47] In February 2020, Chinese researchers found that there is only one amino acid difference in the binding domain of the S protein between the coronaviruses from pangolins and those from humans; however, whole-genome comparison to date found that at most 92% of genetic material was shared between pangolin coronavirus and SARS-CoV-2, which is insufficient to prove pangolins to be the intermediate host.[79]
Pathophysiology
The lungs are the organs most affected by COVID‑19 because the virus accesses host cells via the enzyme angiotensin-converting enzyme 2 (ACE2), which is most abundant in type II alveolar cells of the lungs. The virus uses a special surface glycoprotein called a "spike" (peplomer) to connect to ACE2 and enter the host cell.[80] The density of ACE2 in each tissue correlates with the severity of the disease in that tissue and some have suggested that decreasing ACE2 activity might be protective,[81][82] though another view is that increasing ACE2 using angiotensin II receptor blocker medications could be protective and these hypotheses need to be tested.[83] As the alveolar disease progresses, respiratory failure might develop and death may follow.[82]
The virus also affects gastrointestinal organs as ACE2 is abundantly expressed in the glandular cells of gastric, duodenal and rectal epithelium[84] as well as endothelial cells and enterocytes of the small intestine.[85]
ACE2 is present in the brain, and there is growing evidence of neurological manifestations in people with COVID‑19. It is not certain if the virus can directly infect the brain by crossing the barriers that separate the circulation of the brain and the general circulation. Other coronaviruses are able to infect the brain via a synaptic route to the respiratory centre in the medulla, through mechanoreceptors like pulmonary stretch receptors and chemoreceptors (primarily central chemoreceptors) within the lungs.[medical citation needed] It is possible that dysfunction within the respiratory centre further worsens the ARDS seen in COVID‑19 patients. Common neurological presentations include a loss of smell, headaches, nausea, and vomiting. Encephalopathy has been noted to occur in some patients (and confirmed with imaging), with some reports of detection of the virus after cerebrospinal fluid assays although the presence of oligoclonal bands seems to be a common denominator in these patients.[86]
The virus can cause acute myocardial injury and chronic damage to the cardiovascular system.[87] An acute cardiac injury was found in 12% of infected people admitted to the hospital in Wuhan, China,[88] and is more frequent in severe disease.[89] Rates of cardiovascular symptoms are high, owing to the systemic inflammatory response and immune system disorders during disease progression, but acute myocardial injuries may also be related to ACE2 receptors in the heart.[87] ACE2 receptors are highly expressed in the heart and are involved in heart function.[87][90] A high incidence of thrombosis (31%) and venous thromboembolism (25%) have been found in ICU patients with COVID‑19 infections and may be related to poor prognosis.[91][92] Blood vessel dysfunction and clot formation (as suggested by high D-dimer levels) are thought to play a significant role in mortality, incidences of clots leading to pulmonary embolisms, and ischaemic events within the brain have been noted as complications leading to death in patients infected with SARS-CoV-2. Infection appears to set off a chain of vasoconstrictive responses within the body, constriction of blood vessels within the pulmonary circulation has also been posited as a mechanism in which oxygenation decreases alongside with the presentation of viral pneumonia.[93]
Another common cause of death is complications related to the kidneys[93]—SARS-CoV-2 directly infects kidney cells, as confirmed in post-mortem studies. Acute kidney injury is a common complication and cause of death; this is more significant in patients with already compromised kidney function, especially in people with pre-existing chronic conditions such as hypertension and diabetes which specifically cause nephropathy in the long run.[94]
Autopsies of people who died of COVID‑19 have found diffuse alveolar damage (DAD), and lymphocyte-containing inflammatory infiltrates within the lung.[95]
Immunopathology
Although SARS-COV-2 has a tropism for ACE2-expressing epithelial cells of the respiratory tract, patients with severe COVID‑19 have symptoms of systemic hyperinflammation. Clinical laboratory findings of elevated IL-2, IL-7, IL-6, granulocyte-macrophage colony-stimulating factor (GM-CSF), interferon-γ inducible protein 10 (IP-10), monocyte chemoattractant protein 1 (MCP-1), macrophage inflammatory protein 1-α (MIP-1α), and tumour necrosis factor-α (TNF-α) indicative of cytokine release syndrome (CRS) suggest an underlying immunopathology.[96]
Additionally, people with COVID‑19 and acute respiratory distress syndrome (ARDS) have classical serum biomarkers of CRS, including elevated C-reactive protein (CRP), lactate dehydrogenase (LDH), D-dimer, and ferritin.[97]
Systemic inflammation results in vasodilation, allowing inflammatory lymphocytic and monocytic infiltration of the lung and the heart. In particular, pathogenic GM-CSF-secreting T-cells were shown to correlate with the recruitment of inflammatory IL-6-secreting monocytes and severe lung pathology in COVID‑19 patients.[98] Lymphocytic infiltrates have also been reported at autopsy.[95]
Diagnosis
Main article: COVID-19 testing
Demonstration of a nasopharyngeal swab for COVID-19 testing
CDC rRT-PCR test kit for COVID-19[99]
The WHO has published several testing protocols for the disease.[100] The standard method of testing is real-time reverse transcription polymerase chain reaction (rRT-PCR).[101] The test is typically done on respiratory samples obtained by a nasopharyngeal swab; however, a nasal swab or sputum sample may also be used.[25][102] Results are generally available within a few hours to two days.[103][104] Blood tests can be used, but these require two blood samples taken two weeks apart, and the results have little immediate value.[105] Chinese scientists were able to isolate a strain of the coronavirus and publish the genetic sequence so laboratories across the world could independently develop polymerase chain reaction (PCR) tests to detect infection by the virus.[9][106][107] As of 4 April 2020, antibody tests (which may detect active infections and whether a person had been infected in the past) were in development, but not yet widely used.[108][109][110] The Chinese experience with testing has shown the accuracy is only 60 to 70%.[111] The FDA in the United States approved the first point-of-care test on 21 March 2020 for use at the end of that month.[112]
Diagnostic guidelines released by Zhongnan Hospital of Wuhan University suggested methods for detecting infections based upon clinical features and epidemiological risk. These involved identifying people who had at least two of the following symptoms in addition to a history of travel to Wuhan or contact with other infected people: fever, imaging features of pneumonia, normal or reduced white blood cell count, or reduced lymphocyte count.[113]
A study asked hospitalised COVID‑19 patients to cough into a sterile container, thus producing a saliva sample, and detected the virus in eleven of twelve patients using RT-PCR. This technique has the potential of being quicker than a swab and involving less risk to health care workers (collection at home or in the car).[64]
Along with laboratory testing, chest CT scans may be helpful to diagnose COVID-19 in individuals with a high clinical suspicion of infection but are not recommended for routine screening.[26][27] Bilateral multilobar ground-glass opacities with a peripheral, asymmetric, and posterior distribution are common in early infection.[26] Subpleural dominance, crazy paving (lobular septal thickening with variable alveolar filling), and consolidation may appear as the disease progresses.[26][114]
In late 2019, WHO assigned the emergency ICD-10 disease codes U07.1 for deaths from lab-confirmed SARS-CoV-2 infection and U07.2 for deaths from clinically or epidemiologically diagnosed COVID‑19 without lab-confirmed SARS-CoV-2 infection.[115]
Typical CT imaging findings
CT imaging of rapid progression stage
Pathology
Few data are available about microscopic lesions and the pathophysiology of COVID‑19.[116][117] The main pathological findings at autopsy are:
Macroscopy: pleurisy, pericarditis, lung consolidation and pulmonary oedema
Four types of severity of viral pneumonia can be observed:
minor pneumonia: minor serous exudation, minor fibrin exudation
mild pneumonia: pulmonary oedema, pneumocyte hyperplasia, large atypical pneumocytes, interstitial inflammation with lymphocytic infiltration and multinucleated giant cell formation
severe pneumonia: diffuse alveolar damage (DAD) with diffuse alveolar exudates. DAD is the cause of acute respiratory distress syndrome (ARDS) and severe hypoxemia.
healing pneumonia: organisation of exudates in alveolar cavities and pulmonary interstitial fibrosis
plasmocytosis in BAL[118]
Blood: disseminated intravascular coagulation (DIC);[119] leukoerythroblastic reaction[120]
Liver: microvesicular steatosis
Prevention
See also: 2019–20 coronavirus pandemic § Prevention, flatten the curve, and workplace hazard controls for COVID-19
Progressively stronger mitigation efforts to reduce the number of active cases at any given time—known as "flattening the curve"—allows healthcare services to better manage the same volume of patients.[121][122][123] Likewise, progressively greater increases in healthcare capacity—called raising the line—such as by increasing bed count, personnel, and equipment, helps to meet increased demand.[124]
Mitigation attempts that are inadequate in strictness or duration—such as premature relaxation of distancing rules or stay-at-home orders—can allow a resurgence after the initial surge and mitigation.[122][125]
Preventive measures to reduce the chances of infection include staying at home, avoiding crowded places, keeping distance from others, washing hands with soap and water often and for at least 20 seconds, practising good respiratory hygiene, and avoiding touching the eyes, nose, or mouth with unwashed hands.[126][127][128] The CDC recommends covering the mouth and nose with a tissue when coughing or sneezing and recommends using the inside of the elbow if no tissue is available.[126] Proper hand hygiene after any cough or sneeze is encouraged.[126] The CDC has recommended the use of cloth face coverings in public settings where other social distancing measures are difficult to maintain, in part to limit transmission by asymptomatic individuals.[129] The U.S. National Institutes of Health guidelines do not recommend any medication for prevention of COVID‑19, before or after exposure to the SARS-CoV-2 virus, outside of the setting of a clinical trial.[130]
Social distancing strategies aim to reduce contact of infected persons with large groups by closing schools and workplaces, restricting travel, and cancelling large public gatherings.[131] Distancing guidelines also include that people stay at least 6 feet (1.8 m) apart.[132] There is no medication known to be effective at preventing COVID‑19.[133] After the implementation of social distancing and stay-at-home orders, many regions have been able to sustain an effective transmission rate ("Rt") of less than one, meaning the disease is in remission in those areas.[134]
As a vaccine is not expected until 2021 at the earliest,[135] a key part of managing COVID‑19 is trying to decrease the epidemic peak, known as "flattening the curve".[122] This is done by slowing the infection rate to decrease the risk of health services being overwhelmed, allowing for better treatment of current cases, and delaying additional cases until effective treatments or a vaccine become available.[122][125]
According to the WHO, the use of masks is recommended only if a person is coughing or sneezing or when one is taking care of someone with a suspected infection.[136] For the European Centre for Disease Prevention and Control (ECDC) face masks "... could be considered especially when visiting busy closed spaces ..." but "... only as a complementary measure ..."[137] Several countries have recommended that healthy individuals wear face masks or cloth face coverings (like scarves or bandanas) at least in certain public settings, including China,[138] Hong Kong,[139] Spain,[140] Italy (Lombardy region),[141] and the United States.[129]
Those diagnosed with COVID‑19 or who believe they may be infected are advised by the CDC to stay home except to get medical care, call ahead before visiting a healthcare provider, wear a face mask before entering the healthcare provider's office and when in any room or vehicle with another person, cover coughs and sneezes with a tissue, regularly wash hands with soap and water and avoid sharing personal household items.[30][142] The CDC also recommends that individuals wash hands often with soap and water for at least 20 seconds, especially after going to the toilet or when hands are visibly dirty, before eating and after blowing one's nose, coughing or sneezing. It further recommends using an alcohol-based hand sanitiser with at least 60% alcohol, but only when soap and water are not readily available.[126]
For areas where commercial hand sanitisers are not readily available, the WHO provides two formulations for local production. In these formulations, the antimicrobial activity arises from ethanol or isopropanol. Hydrogen peroxide is used to help eliminate bacterial spores in the alcohol; it is "not an active substance for hand antisepsis". Glycerol is added as a humectant.[143]
Prevention efforts are multiplicative, with effects far beyond that of a single spread. Each avoided case leads to more avoided cases down the line, which in turn can stop the outbreak in its tracks.
File:COVID19 W ENG.ogv
Handwashing instructions
Management
People are managed with supportive care, which may include fluid therapy, oxygen support, and supporting other affected vital organs.[144][145][146] The CDC recommends that those who suspect they carry the virus wear a simple face mask.[30] Extracorporeal membrane oxygenation (ECMO) has been used to address the issue of respiratory failure, but its benefits are still under consideration.[41][147] Personal hygiene and a healthy lifestyle and diet have been recommended to improve immunity.[148] Supportive treatments may be useful in those with mild symptoms at the early stage of infection.[149]
The WHO, the Chinese National Health Commission, and the United States' National Institutes of Health have published recommendations for taking care of people who are hospitalised with COVID‑19.[130][150][151] Intensivists and pulmonologists in the U.S. have compiled treatment recommendations from various agencies into a free resource, the IBCC.[152][153]
Medications
See also: Coronavirus disease 2019 § Research
As of April 2020, there is no specific treatment for COVID‑19.[6][133] Research is, however, ongoing. For symptoms, some medical professionals recommend paracetamol (acetaminophen) over ibuprofen for first-line use.[154][155][156] The WHO and NIH do not oppose the use of non-steroidal anti-inflammatory drugs (NSAIDs) such as ibuprofen for symptoms,[130][157] and the FDA says currently there is no evidence that NSAIDs worsen COVID‑19 symptoms.[158]
While theoretical concerns have been raised about ACE inhibitors and angiotensin receptor blockers, as of 19 March 2020, these are not sufficient to justify stopping these medications.[130][159][160][161] Steroids, such as methylprednisolone, are not recommended unless the disease is complicated by acute respiratory distress syndrome.[162][163]
Medications to prevent blood clotting have been suggested for treatment,[91] and anticoagulant therapy with low molecular weight heparin appears to be associated with better outcomes in severe COVID‐19 showing signs of coagulopathy (elevated D-dimer).[164]
Protective equipment
See also: COVID-19 related shortages
The CDC recommends four steps to putting on personal protective equipment (PPE).[165]
Precautions must be taken to minimise the risk of virus transmission, especially in healthcare settings when performing procedures that can generate aerosols, such as intubation or hand ventilation.[166] For healthcare professionals caring for people with COVID‑19, the CDC recommends placing the person in an Airborne Infection Isolation Room (AIIR) in addition to using standard precautions, contact precautions, and airborne precautions.[167]
The CDC outlines the guidelines for the use of personal protective equipment (PPE) during the pandemic. The recommended gear is a PPE gown, respirator or facemask, eye protection, and medical gloves.[168][169]
When available, respirators (instead of facemasks) are preferred.[170] N95 respirators are approved for industrial settings but the FDA has authorised the masks for use under an Emergency Use Authorisation (EUA). They are designed to protect from airborne particles like dust but effectiveness against a specific biological agent is not guaranteed for off-label uses.[171] When masks are not available, the CDC recommends using face shields or, as a last resort, homemade masks.[172]
Mechanical ventilation
Most cases of COVID‑19 are not severe enough to require mechanical ventilation or alternatives, but a percentage of cases are.[173][174] The type of respiratory support for individuals with COVID‑19 related respiratory failure is being actively studied for people in the hospital, with some evidence that intubation can be avoided with a high flow nasal cannula or bi-level positive airway pressure.[175] Whether either of these two leads to the same benefit for people who are critically ill is not known.[176] Some doctors prefer staying with invasive mechanical ventilation when available because this technique limits the spread of aerosol particles compared to a high flow nasal cannula.[173]
Severe cases are most common in older adults (those older than 60 years,[173] and especially those older than 80 years).[177] Many developed countries do not have enough hospital beds per capita, which limits a health system's capacity to handle a sudden spike in the number of COVID‑19 cases severe enough to require hospitalisation.[178] This limited capacity is a significant driver behind calls to flatten the curve.[178] One study in China found 5% were admitted to intensive care units, 2.3% needed mechanical support of ventilation, and 1.4% died.[41] In China, approximately 30% of people in hospital with COVID‑19 are eventually admitted to ICU.[4]
Acute respiratory distress syndrome
Main article: Acute respiratory distress syndrome
Mechanical ventilation becomes more complex as acute respiratory distress syndrome (ARDS) develops in COVID‑19 and oxygenation becomes increasingly difficult.[179] Ventilators capable of pressure control modes and high PEEP[180] are needed to maximise oxygen delivery while minimising the risk of ventilator-associated lung injury and pneumothorax.[181] High PEEP may not be available on older ventilators.
Options for ARDS[179]
TherapyRecommendations
High-flow nasal oxygenFor SpO2 <93%. May prevent the need for intubation and ventilation
Tidal volume6mL per kg and can be reduced to 4mL/kg
Plateau airway pressureKeep below 30 cmH2O if possible (high respiratory rate (35 per minute) may be required)
Positive end-expiratory pressureModerate to high levels
Prone positioningFor worsening oxygenation
Fluid managementGoal is a negative balance of 0.5–1.0L per day
AntibioticsFor secondary bacterial infections
GlucocorticoidsNot recommended
Experimental treatment
See also: § Research
Research into potential treatments started in January 2020,[182] and several antiviral drugs are in clinical trials.[183][184] Remdesivir appears to be the most promising.[133] Although new medications may take until 2021 to develop,[185] several of the medications being tested are already approved for other uses or are already in advanced testing.[186] Antiviral medication may be tried in people with severe disease.[144] The WHO recommended volunteers take part in trials of the effectiveness and safety of potential treatments.[187]
The FDA has granted temporary authorisation to convalescent plasma as an experimental treatment in cases where the person's life is seriously or immediately threatened. It has not undergone the clinical studies needed to show it is safe and effective for the disease.[188][189][190]
Information technology
See also: Contact tracing and Government by algorithm
In February 2020, China launched a mobile app to deal with the disease outbreak.[191] Users are asked to enter their name and ID number. The app can detect 'close contact' using surveillance data and therefore a potential risk of infection. Every user can also check the status of three other users. If a potential risk is detected, the app not only recommends self-quarantine, it also alerts local health officials.[192]
Big data analytics on cellphone data, facial recognition technology, mobile phone tracking, and artificial intelligence are used to track infected people and people whom they contacted in South Korea, Taiwan, and Singapore.[193][194] In March 2020, the Israeli government enabled security agencies to track mobile phone data of people supposed to have coronavirus. The measure was taken to enforce quarantine and protect those who may come into contact with infected citizens.[195] Also in March 2020, Deutsche Telekom shared aggregated phone location data with the German federal government agency, Robert Koch Institute, to research and prevent the spread of the virus.[196] Russia deployed facial recognition technology to detect quarantine breakers.[197] Italian regional health commissioner Giulio Gallera said he has been informed by mobile phone operators that "40% of people are continuing to move around anyway".[198] German government conducted a 48 hours weekend hackathon with more than 42.000 participants.[199][200] Two million people in the UK used an app developed in March 2020 by King's College London and Zoe to track people with COVID‑19 symptoms.[201] Also, the president of Estonia, Kersti Kaljulaid, made a global call for creative solutions against the spread of coronavirus.[202]
Psychological support
See also: Mental health during the 2019–20 coronavirus pandemic
Individuals may experience distress from quarantine, travel restrictions, side effects of treatment, or fear of the infection itself. To address these concerns, the National Health Commission of China published a national guideline for psychological crisis intervention on 27 January 2020.[203][204]
The Lancet published a 14-page call for action focusing on the UK and stated conditions were such that a range of mental health issues was likely to become more common. BBC quoted Rory O'Connor in saying, "Increased social isolation, loneliness, health anxiety, stress and an economic downturn are a perfect storm to harm people's mental health and wellbeing."[205][206]
Prognosis
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The severity of diagnosed cases in China
The severity of diagnosed COVID-19 cases in China[207]
Case fatality rates for COVID-19 by age by country.
Case fatality rates by age group:
China, as of 11 February 2020[208]
South Korea, as of 15 April 2020[209]
Spain, as of 24 April 2020[210]
Italy, as of 23 April 2020[211]
Case fatality rate depending on other health problems
Case fatality rate in China depending on other health problems. Data through 11 February 2020.[208]
Case fatality rate by country and number of cases
The number of deaths vs total cases by country and approximate case fatality rate[212]
The severity of COVID‑19 varies. The disease may take a mild course with few or no symptoms, resembling other common upper respiratory diseases such as the common cold. Mild cases typically recover within two weeks, while those with severe or critical diseases may take three to six weeks to recover. Among those who have died, the time from symptom onset to death has ranged from two to eight weeks.[47]
Children make up a small proportion of reported cases, with about 1% of cases being under 10 years, and 4% aged 10-19 years.[22] They are likely to have milder symptoms and a lower chance of severe disease than adults; in those younger than 50 years, the risk of death is less than 0.5%, while in those older than 70 it is more than 8%.[213][214][215] Pregnant women may be at higher risk for severe infection with COVID-19 based on data from other similar viruses, like SARS and MERS, but data for COVID-19 is lacking.[216][217] In China, children acquired infections mainly through close contact with their parents or other family members who lived in Wuhan or had traveled there.[213]
In some people, COVID‑19 may affect the lungs causing pneumonia. In those most severely affected, COVID-19 may rapidly progress to acute respiratory distress syndrome (ARDS) causing respiratory failure, septic shock, or multi-organ failure.[218][219] Complications associated with COVID‑19 include sepsis, abnormal clotting, and damage to the heart, kidneys, and liver. Clotting abnormalities, specifically an increase in prothrombin time, have been described in 6% of those admitted to hospital with COVID-19, while abnormal kidney function is seen in 4% of this group.[220] Approximately 20-30% of people who present with COVID‑19 demonstrate elevated liver enzymes (transaminases).[133] Liver injury as shown by blood markers of liver damage is frequently seen in severe cases.[221]
Some studies have found that the neutrophil to lymphocyte ratio (NLR) may be helpful in early screening for severe illness.[222]
Most of those who die of COVID‑19 have pre-existing (underlying) conditions, including hypertension, diabetes mellitus, and cardiovascular disease.[223] The Istituto Superiore di Sanità reported that out of 8.8% of deaths where medical charts were available for review, 97.2% of sampled patients had at least one comorbidity with the average patient having 2.7 diseases.[224] According to the same report, the median time between the onset of symptoms and death was ten days, with five being spent hospitalised. However, patients transferred to an ICU had a median time of seven days between hospitalisation and death.[224] In a study of early cases, the median time from exhibiting initial symptoms to death was 14 days, with a full range of six to 41 days.[225] In a study by the National Health Commission (NHC) of China, men had a death rate of 2.8% while women had a death rate of 1.7%.[226] Histopathological examinations of post-mortem lung samples show diffuse alveolar damage with cellular fibromyxoid exudates in both lungs. Viral cytopathic changes were observed in the pneumocytes. The lung picture resembled acute respiratory distress syndrome (ARDS).[47] In 11.8% of the deaths reported by the National Health Commission of China, heart damage was noted by elevated levels of troponin or cardiac arrest.[49] According to March data from the United States, 89% of those hospitalised had preexisting conditions.[227]
The availability of medical resources and the socioeconomics of a region may also affect mortality.[228] Estimates of the mortality from the condition vary because of those regional differences,[229] but also because of methodological difficulties. The under-counting of mild cases can cause the mortality rate to be overestimated.[230] However, the fact that deaths are the result of cases contracted in the past can mean the current mortality rate is underestimated.[231][232] Smokers were 1.4 times more likely to have severe symptoms of COVID‑19 and approximately 2.4 times more likely to require intensive care or die compared to non-smokers.[233]
Concerns have been raised about long-term sequelae of the disease. The Hong Kong Hospital Authority found a drop of 20% to 30% in lung capacity in some people who recovered from the disease, and lung scans suggested organ damage.[234] This may also lead to post-intensive care syndrome following recovery.[235]
Case fatality rates (%) by age and country
Age0–910–1920–2930–3940–4950–5960–6970–7980-8990+
China as of 11 February[208]0.00.20.20.20.41.33.68.014.8
Denmark as of 25 April[236]0.24.515.524.940.7
Italy as of 23 April[211]0.20.00.10.40.92.610.024.930.826.1
Netherlands as of 17 April[237]0.00.30.10.20.51.57.623.230.029.3
Portugal as of 24 April[238]0.00.00.00.00.30.62.88.516.5
S. Korea as of 15 April[209]0.00.00.00.10.20.72.59.722.2
Spain as of 24 April[210]0.30.40.30.30.61.34.413.220.320.1
Switzerland as of 25 April[239]0.90.00.00.10.00.52.710.124.0
Case fatality rates (%) by age in the United States
Age0–1920–4445–5455–6465–7475–8485+
United States as of 16 March[240]0.00.1–0.20.5–0.81.4–2.62.7–4.94.3–10.510.4–27.3
Note: The lower bound includes all cases. The upper bound excludes cases that were missing data.
Estimate of infection fatality rates and probability of severe disease course (%) by age based on cases from China[241]
0–910–1920–2930–3940–4950–5960–6970–7980+
Severe disease0.0
(0.0–0.0)0.04
(0.02–0.08)1.0
(0.62–2.1)3.4
(2.0–7.0)4.3
(2.5–8.7)8.2
(4.9–17)11
(7.0–24)17
(9.9–34)18
(11–38)
Death0.0016
(0.00016–0.025)0.0070
(0.0015–0.050)0.031
(0.014–0.092)0.084
(0.041–0.19)0.16
(0.076–0.32)0.60
(0.34–1.3)1.9
(1.1–3.9)4.3
(2.5–8.4)7.8
(3.8–13)
Total infection fatality rate is estimated to be 0.66% (0.39–1.3). Infection fatality rate is fatality per all infected individuals, regardless of whether they were diagnosed or had any symptoms. Numbers in parentheses are 95% credible intervals for the estimates.
Reinfection
As of March 2020, it was unknown if past infection provides effective and long-term immunity in people who recover from the disease.[242] Immunity is seen as likely, based on the behaviour of other coronaviruses,[243] but cases in which recovery from COVID‑19 have been followed by positive tests for coronavirus at a later date have been reported.[244][245][246][247] These cases are believed to be worsening of a lingering infection rather than re-infection.[247]
History
Main article: Timeline of the 2019–20 coronavirus pandemic
The virus is thought to be natural and has an animal origin,[77] through spillover infection.[248] The actual origin is unknown, but by December 2019 the spread of infection was almost entirely driven by human-to-human transmission.[208][249] A study of the first 41 cases of confirmed COVID‑19, published in January 2020 in The Lancet, revealed the earliest date of onset of symptoms as 1 December 2019.[250][251][252] Official publications from the WHO reported the earliest onset of symptoms as 8 December 2019.[253] Human-to-human transmission was confirmed by the WHO and Chinese authorities by 20 January 2020.[254][255]
Epidemiology
Main article: 2019–20 coronavirus pandemic
Several measures are commonly used to quantify mortality.[256] These numbers vary by region and over time and are influenced by the volume of testing, healthcare system quality, treatment options, time since the initial outbreak, and population characteristics such as age, sex, and overall health.[257]
The death-to-case ratio reflects the number of deaths divided by the number of diagnosed cases within a given time interval. Based on Johns Hopkins University statistics, the global death-to-case ratio is 7.0% (203,044/2,899,830) as of 26 April 2020.[7] The number varies by region.[258]
Other measures include the case fatality rate (CFR), which reflects the percent of diagnosed individuals who die from a disease, and the infection fatality rate (IFR), which reflects the percent of infected individuals (diagnosed and undiagnosed) who die from a disease. These statistics are not time-bound and follow a specific population from infection through case resolution. Many academics have attempted to calculate these numbers for specific populations.[259]
Total confirmed cases over time
Total deaths over time
Total confirmed cases of COVID‑19 per million people, 10 April 2020[260]
Total confirmed deaths due to COVID‑19 per million people, 10 April 2020[261]
Infection fatality rate
Our World in Data states that as of March 25, 2020, the infection fatality rate (IFR) cannot be accurately calculated.[262] In February, the World Health Organization estimated the IFR at 0.94%, with a confidence interval between 0.37 percent to 2.9 percent.[263] The University of Oxford Centre for Evidence-Based Medicine (CEBM) estimated a global CFR of 0.72 percent and IFR of 0.1 percent to 0.36 percent.[264] According to CEBM, random antibody testing in Germany suggested an IFR of 0.37 percent there.[264] Firm lower limits to local infection fatality rates were established, such as in Bergamo province, where 0.57% of the population has died, leading to a minimum IFR of 0.57% in the province. This population fatality rate (PFR) minimum increases as more people get infected and run through their disease.[265][266] Similarly, as of April 22 in the New York City area, there were 15,411 deaths confirmed from COVID-19, and 19,200 excess deaths.[267] Very recently, the first results of antibody testing have come in, but there are no valid scientific reports based on them available yet. A Bloomberg Opinion piece provides a survey.[268][269]
Sex differences
Main article: Gendered impact of the 2019–20 coronavirus pandemic
The impact of the pandemic and its mortality rate are different for men and women.[270] Mortality is higher in men in studies conducted in China and Italy.[271][272][273] The highest risk for men is in their 50s, with the gap between men and women closing only at 90.[273] In China, the death rate was 2.8 percent for men and 1.7 percent for women.[273] The exact reasons for this sex-difference are not known, but genetic and behavioural factors could be a reason.[270] Sex-based immunological differences, a lower prevalence of smoking in women, and men developing co-morbid conditions such as hypertension at a younger age than women could have contributed to the higher mortality in men.[273] In Europe, of those infected with COVID‑19, 57% were men; of those infected with COVID‑19 who also died, 72% were men.[274] As of April 2020, the U.S. government is not tracking sex-related data of COVID‑19 infections.[275] Research has shown that viral illnesses like Ebola, HIV, influenza, and SARS affect men and women differently.[275] A higher percentage of health workers, particularly nurses, are women, and they have a higher chance of being exposed to the virus.[276] School closures, lockdowns, and reduced access to healthcare following the 2019–20 coronavirus pandemic may differentially affect the genders and possibly exaggerate existing gender disparity.[270][277]
Society and culture
Name
During the initial outbreak in Wuhan, China, the virus and disease were commonly referred to as "coronavirus" and "Wuhan coronavirus",[278][279][280] with the disease sometimes called "Wuhan pneumonia".[281][282] In the past, many diseases have been named after geographical locations, such as the Spanish flu,[283] Middle East Respiratory Syndrome, and Zika virus.[284]
In January 2020, the World Health Organisation recommended 2019-nCov[285] and 2019-nCoV acute respiratory disease[286] as interim names for the virus and disease per 2015 guidance and international guidelines against using geographical locations (e.g. Wuhan, China), animal species or groups of people in disease and virus names to prevent social stigma.[287][288][289]
The official names COVID‑19 and SARS-CoV-2 were issued by the WHO on 11 February 2020.[290] WHO chief Tedros Adhanom Ghebreyesus explained: CO for corona, VI for virus, D for disease and 19 for when the outbreak was first identified (31 December 2019).[291] The WHO additionally uses "the COVID‑19 virus" and "the virus responsible for COVID‑19" in public communications.[290] Both the disease and virus are commonly referred to as "coronavirus" in the media and public discourse.
Misinformation
Main article: Misinformation related to the 2019–20 coronavirus pandemic
After the initial outbreak of COVID‑19, conspiracy theories, misinformation, and disinformation emerged regarding the origin, scale, prevention, treatment, and other aspects of the disease and rapidly spread online.[292][293][294][295]
Protests
Beginning April 17, 2020, news media began reporting on a wave of demonstrations protesting against state-mandated quarantine restrictions in in Michigan, Ohio, and Kentucky.[296][297]
Other animals
Humans appear to be capable of spreading the virus to some other animals. A domestic cat in Liège, Belgium, tested positive after it started showing symptoms (diarrhoea, vomiting, shortness of breath) a week later than its owner, who was also positive.[298] Tigers at the Bronx Zoo in New York, United States, tested positive for the virus and showed symptoms of COVID‑19, including a dry cough and loss of appetite.[299]
A study on domesticated animals inoculated with the virus found that cats and ferrets appear to be "highly susceptible" to the disease, while dogs appear to be less susceptible, with lower levels of viral replication. The study failed to find evidence of viral replication in pigs, ducks, and chickens.[300]
Research
Main article: COVID-19 drug development
No medication or vaccine is approved to treat the disease.[186] International research on vaccines and medicines in COVID‑19 is underway by government organisations, academic groups, and industry researchers.[301][302] In March, the World Health Organisation initiated the "SOLIDARITY Trial" to assess the treatment effects of four existing antiviral compounds with the most promise of efficacy.[303]
Vaccine
Main article: COVID-19 vaccine
There is no available vaccine, but various agencies are actively developing vaccine candidates. Previous work on SARS-CoV is being used because both SARS-CoV and SARS-CoV-2 use the ACE2 receptor to enter human cells.[304] Three vaccination strategies are being investigated. First, researchers aim to build a whole virus vaccine. The use of such a virus, be it inactive or dead, aims to elicit a prompt immune response of the human body to a new infection with COVID‑19. A second strategy, subunit vaccines, aims to create a vaccine that sensitises the immune system to certain subunits of the virus. In the case of SARS-CoV-2, such research focuses on the S-spike protein that helps the virus intrude the ACE2 enzyme receptor. A third strategy is that of the nucleic acid vaccines (DNA or RNA vaccines, a novel technique for creating a vaccination). Experimental vaccines from any of these strategies would have to be tested for safety and efficacy.[305]
On 16 March 2020, the first clinical trial of a vaccine started with four volunteers in Seattle, United States. The vaccine contains a harmless genetic code copied from the virus that causes the disease.[306]
Antibody-dependent enhancement has been suggested as a potential challenge for vaccine development for SARS-COV-2, but this is controversial.[307]
Medications
Main article: COVID-19 drug repurposing research
At least 29 phase II–IV efficacy trials in COVID‑19 were concluded in March 2020 or scheduled to provide results in April from hospitals in China.[308][309] There are more than 300 active clinical trials underway as of April 2020.[133] Seven trials were evaluating already approved treatments, including four studies on hydroxychloroquine or chloroquine.[309] Repurposed antiviral drugs make up most of the Chinese research, with nine phase III trials on remdesivir across several countries due to report by the end of April.[308][309] Other candidates in trials include vasodilators, corticosteroids, immune therapies, lipoic acid, bevacizumab, and recombinant angiotensin-converting enzyme 2.[309]
The COVID‑19 Clinical Research Coalition has goals to 1) facilitate rapid reviews of clinical trial proposals by ethics committees and national regulatory agencies, 2) fast-track approvals for the candidate therapeutic compounds, 3) ensure standardised and rapid analysis of emerging efficacy and safety data and 4) facilitate sharing of clinical trial outcomes before publication.[310][311]
Several existing medications are being evaluated for the treatment of COVID‑19,[186] including remdesivir, chloroquine, hydroxychloroquine, lopinavir/ritonavir, and lopinavir/ritonavir combined with interferon beta.[303][312] There is tentative evidence for efficacy by remdesivir, as of March 2020.[313][314] Clinical improvement was observed in patients treated with compassionate-use remdesivir.[315] Remdesivir inhibits SARS-CoV-2 in vitro.[316] Phase III clinical trials are underway in the U.S., China, and Italy.[186][308][317]
In 2020, a trial found that lopinavir/ritonavir was ineffective in the treatment of severe illness.[318] Nitazoxanide has been recommended for further in vivo study after demonstrating low concentration inhibition of SARS-CoV-2.[316]
There are mixed results as of 3 April 2020 as to the effectiveness of hydroxychloroquine as a treatment for COVID‑19, with some studies showing little or no improvement.[319][320] The studies of chloroquine and hydroxychloroquine with or without azithromycin have major limitations that have prevented the medical community from embracing these therapies without further study.[133]
Oseltamivir does not inhibit SARS-CoV-2 in vitro and has no known role in COVID‑19 treatment.[133]
Anti-cytokine storm
Cytokine release syndrome (CRS) can be a complication in the later stages of severe COVID‑19. There is preliminary evidence that hydroxychloroquine may have anti-cytokine storm properties.[321]
Tocilizumab has been included in treatment guidelines by China's National Health Commission after a small study was completed.[322][323] It is undergoing a phase 2 non-randomised trial at the national level in Italy after showing positive results in people with severe disease.[324][325] Combined with a serum ferritin blood test to identify cytokine storms, it is meant to counter such developments, which are thought to be the cause of death in some affected people.[326][327][328] The interleukin-6 receptor antagonist was approved by the FDA to undergo a phase III clinical trial assessing the medication's impact on COVID‑19 based on retrospective case studies for the treatment of steroid-refractory cytokine release syndrome induced by a different cause, CAR T cell therapy, in 2017.[329] To date, there is no randomised, controlled evidence that tocilizumab is an efficacious treatment for CRS. Prophylactic tocilizumab has been shown to increase serum IL-6 levels by saturating the IL-6R, driving IL-6 across the blood-brain barrier, and exacerbating neurotoxicity while having no impact on the incidence of CRS.[330]
Lenzilumab, an anti-GM-CSF monoclonal antibody, is protective in murine models for CAR T cell-induced CRS and neurotoxicity and is a viable therapeutic option due to the observed increase of pathogenic GM-CSF secreting T-cells in hospitalised patients with COVID‑19.[331]
The Feinstein Institute of Northwell Health announced in March a study on "a human antibody that may prevent the activity" of IL-6.[332]
Passive antibodies
Transferring purified and concentrated antibodies produced by the immune systems of those who have recovered from COVID‑19 to people who need them is being investigated as a non-vaccine method of passive immunisation.[333] This strategy was tried for SARS with inconclusive results.[333] Viral neutralisation is the anticipated mechanism of action by which passive antibody therapy can mediate defence against SARS-CoV-2. Other mechanisms, however, such as antibody-dependent cellular cytotoxicity and/or phagocytosis, may be possible.[333] Other forms of passive antibody therapy, for example, using manufactured monoclonal antibodies, are in development.[333] Production of convalescent serum, which consists of the liquid portion of the blood from recovered patients and contains antibodies specific to this virus, could be increased for quicker deployment.[334]
From Wikipedia, the free encyclopedia
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This article is about the group of viruses. For the disease involved in the 2019–20 coronavirus pandemic, see Coronavirus disease 2019. For the virus that causes this disease, see Severe acute respiratory syndrome coronavirus 2.
Orthocoronavirinae
Coronaviruses 004 lores.jpg
Transmission electron micrograph (TEM) of avian infectious bronchitis virus
SARS-CoV-2 without background.png
Illustration of the morphology of coronaviruses; the club-shaped viral spike peplomers, colored red, create the look of a corona surrounding the virion when observed with an electron microscope.
Virus classification e
(unranked):Virus
Realm:Riboviria
Phylum:incertae sedis
Order:Nidovirales
Family:Coronaviridae
Subfamily:Orthocoronavirinae
Genera[1]
Alphacoronavirus
Betacoronavirus
Gammacoronavirus
Deltacoronavirus
Synonyms[2][3][4]
Coronavirinae
Coronaviruses are a group of related viruses that cause diseases in mammals and birds. In humans, coronaviruses cause respiratory tract infections that can range from mild to lethal. Mild illnesses include some cases of the common cold (which has other possible causes, predominantly rhinoviruses), while more lethal varieties can cause SARS, MERS, and COVID-19. Symptoms in other species vary: in chickens, they cause an upper respiratory tract disease, while in cows and pigs they cause diarrhea. There are yet to be vaccines or antiviral drugs to prevent or treat human coronavirus infections.
Coronaviruses constitute the subfamily Orthocoronavirinae, in the family Coronaviridae, order Nidovirales, and realm Riboviria.[5][6] They are enveloped viruses with a positive-sense single-stranded RNA genome and a nucleocapsid of helical symmetry. The genome size of coronaviruses ranges from approximately 26 to 32 kilobases, one of the largest among RNA viruses.[7] They have characteristic club-shaped spikes that project from their surface, which in electron micrographs create an image reminiscent of the solar corona from which their name derives.[8]
Contents
1Discovery
2Etymology
3Morphology
4Genome
5Life cycle
5.1Entry
5.2Replication
5.3Release
6Transmission
7Taxonomy
8Evolution
9Human coronaviruses
10Outbreaks of coronavirus diseases
10.1Severe acute respiratory syndrome (SARS)
10.2Middle East respiratory syndrome (MERS)
10.3Coronavirus disease 2019 (COVID-19)
11Other animals
11.1Diseases caused
11.2Domestic animals
12Genomic cis-acting elements
13Genome packaging
14See also
15References
16Further reading
Discovery
Coronaviruses were first discovered in the 1930s when an acute respiratory infection of domesticated chickens was shown to be caused by infectious bronchitis virus (IBV). In the 1940s, two more animal coronaviruses, mouse hepatitis virus (MHV) and transmissible gastroenteritis virus (TGEV), were isolated.[9]
Human coronaviruses were discovered in the 1960s.[10] The earliest ones studied were from human patients with the common cold, which were later named human coronavirus 229E and human coronavirus OC43.[11] Other human coronaviruses have since been identified, including SARS-CoV in 2003, HCoV NL63 in 2004, HKU1 in 2005, MERS-CoV in 2012, and SARS-CoV-2 in 2019. Most of these have involved serious respiratory tract infections.
Etymology
The name "coronavirus" is derived from Latin corona, meaning "crown" or "wreath", itself a borrowing from Greek κορώνη korṓnē, "garland, wreath". The name refers to the characteristic appearance of virions (the infective form of the virus) by electron microscopy, which have a fringe of large, bulbous surface projections creating an image reminiscent of a crown or of a solar corona. This morphology is created by the viral spike peplomers, which are proteins on the surface of the virus.[8][12]
Morphology
Cross-sectional model of a coronavirus
Cross-sectional model of a coronavirus
Coronaviruses are large pleomorphic spherical particles with bulbous surface projections.[13] The average diameter of the virus particles is around 120 nm (.12 μm). The diameter of the envelope is ~80 nm (.08 μm) and the spikes are ~20 nm (.02 μm) long. The envelope of the virus in electron micrographs appears as a distinct pair of electron dense shells.[14][15]
The viral envelope consists of a lipid bilayer where the membrane (M), envelope (E) and spike (S) structural proteins are anchored.[16] A subset of coronaviruses (specifically the members of betacoronavirus subgroup A) also have a shorter spike-like surface protein called hemagglutinin esterase (HE).[5]
Inside the envelope, there is the nucleocapsid, which is formed from multiple copies of the nucleocapsid (N) protein, which are bound to the positive-sense single-stranded RNA genome in a continuous beads-on-a-string type conformation.[15][17] The lipid bilayer envelope, membrane proteins, and nucleocapsid protect the virus when it is outside the host cell.[18]
Genome
See also: Severe acute respiratory syndrome-related coronavirus § Genome
Schematic representation of the genome organization and functional domains of S protein for SARS-CoV and MERS-CoV
Coronaviruses contain a positive-sense, single-stranded RNA genome. The genome size for coronaviruses ranges from 26.4 to 31.7 kilobases.[7] The genome size is one of the largest among RNA viruses. The genome has a 5′ methylated cap and a 3′ polyadenylated tail.[15]
The genome organization for a coronavirus is 5′-leader-UTR-replicase/transcriptase-spike (S)-envelope (E)-membrane (M)-nucleocapsid (N)-3′UTR-poly (A) tail. The open reading frames 1a and 1b, which occupy the first two-thirds of the genome, encode the replicase/transcriptase polyprotein. The replicase/transcriptase polyprotein self cleaves to form nonstructural proteins.[15]
The later reading frames encode the four major structural proteins: spike, envelope, membrane, and nucleocapsid.[19] Interspersed between these reading frames are the reading frames for the accessory proteins. The number of accessory proteins and their function is unique depending on the specific coronavirus.[15]
Life cycle
Entry
The life cycle of a coronavirus
Infection begins when the viral spike (S) glycoprotein attaches to its complementary host cell receptor. After attachment, a protease of the host cell cleaves and activates the receptor-attached spike protein. Depending on the host cell protease available, cleavage and activation allows the virus to enter the host cell by endocytosis or direct fusion of the viral envelop with the host membrane.[20]
On entry into the host cell, the virus particle is uncoated, and its genome enters the cell cytoplasm.[15] The coronavirus RNA genome has a 5′ methylated cap and a 3′ polyadenylated tail, which allows the RNA to attach to the host cell's ribosome for translation.[15] The host ribosome translates the initial overlapping open reading frame of the virus genome and forms a long polyprotein. The polyprotein has its own proteases which cleave the polyprotein into multiple nonstructural proteins.[15]
Replication
A number of the nonstructural proteins coalesce to form a multi-protein replicase-transcriptase complex (RTC). The main replicase-transcriptase protein is the RNA-dependent RNA polymerase (RdRp). It is directly involved in the replication and transcription of RNA from an RNA strand. The other nonstructural proteins in the complex assist in the replication and transcription process. The exoribonuclease nonstructural protein, for instance, provides extra fidelity to replication by providing a proofreading function which the RNA-dependent RNA polymerase lacks.[21]
One of the main functions of the complex is to replicate the viral genome. RdRp directly mediates the synthesis of negative-sense genomic RNA from the positive-sense genomic RNA. This is followed by the replication of positive-sense genomic RNA from the negative-sense genomic RNA.[15] The other important function of the complex is to transcribe the viral genome. RdRp directly mediates the synthesis of negative-sense subgenomic RNA molecules from the positive-sense genomic RNA. This is followed by the transcription of these negative-sense subgenomic RNA molecules to their corresponding positive-sense mRNAs.[15]
Release
The replicated positive-sense genomic RNA becomes the genome of the progeny viruses. The mRNAs are gene transcripts of the last third of the virus genome after the initial overlapping reading frame. These mRNAs are translated by the host's ribosomes into the structural proteins and a number of accessory proteins.[15] RNA translation occurs inside the endoplasmic reticulum. The viral structural proteins S, E, and M move along the secretory pathway into the Golgi intermediate compartment. There, the M proteins direct most protein-protein interactions required for assembly of viruses following its binding to the nucleocapsid.[22] Progeny viruses are then released from the host cell by exocytosis through secretory vesicles.[22]
Transmission
The interaction of the coronavirus spike protein with its complement host cell receptor is central in determining the tissue tropism, infectivity, and species range of the virus.[23][24] The SARS coronavirus, for example, infects human cells by attaching to the angiotensin-converting enzyme 2 (ACE2) receptor.[25]
Taxonomy
For a more detailed list of members, see Coronaviridae.
Phylogenetic tree of coronaviruses
The scientific name for coronavirus is Orthocoronavirinae or Coronavirinae.[2][3][4] Coronavirus belongs to the family of Coronaviridae.
Genus: Alphacoronavirus
Species: Human coronavirus 229E, Human coronavirus NL63, Miniopterus bat coronavirus 1, Miniopterus bat coronavirus HKU8, Porcine epidemic diarrhea virus, Rhinolophus bat coronavirus HKU2, Scotophilus bat coronavirus 512
Genus Betacoronavirus; type species: Murine coronavirus
Species: Betacoronavirus 1 (Human coronavirus OC43), Human coronavirus HKU1, Murine coronavirus, Pipistrellus bat coronavirus HKU5, Rousettus bat coronavirus HKU9, Severe acute respiratory syndrome-related coronavirus (SARS-CoV, SARS-CoV-2), Tylonycteris bat coronavirus HKU4, Middle East respiratory syndrome-related coronavirus, Hedgehog coronavirus 1 (EriCoV)
Genus Gammacoronavirus; type species: Infectious bronchitis virus
Species: Beluga whale coronavirus SW1, Infectious bronchitis virus
Genus Deltacoronavirus; type species: Bulbul coronavirus HKU11
Species: Bulbul coronavirus HKU11, Porcine coronavirus HKU15
Evolution
The most recent common ancestor (MRCA) of all coronaviruses has been estimated to have existed as recently as 8000 BCE, though some models place the MRCA as far back as 55 million years or more, implying long term coevolution with bats.[26] The MRCAs of the alphacoronavirus line has been placed at about 2400 BCE, the betacoronavirus line at 3300 BCE, the gammacoronavirus line at 2800 BCE, and the deltacoronavirus line at about 3000 BCE. It appears that bats and birds, as warm-blooded flying vertebrates, are ideal hosts for the coronavirus gene source (with bats for alphacoronavirus and betacoronavirus, and birds for gammacoronavirus and deltacoronavirus) to fuel coronavirus evolution and dissemination.[27]
Bovine coronavirus and canine respiratory coronaviruses diverged from a common ancestor recently (~ 1950).[28] Bovine coronavirus and human coronavirus OC43 diverged around the 1890s. Bovine coronavirus diverged from the equine coronavirus species at the end of the 18th century.[29]
The MRCA of human coronavirus OC43 has been dated to the 1950s.[30]
MERS-CoV, although related to several bat coronavirus species, appears to have diverged from these several centuries ago.[31] The human coronavirus NL63 and a bat coronavirus shared an MRCA 563–822 years ago.[32]
The most closely related bat coronavirus and SARS-CoV diverged in 1986.[33] A path of evolution of the SARS virus and keen relationship with bats have been proposed. The authors suggest that the coronaviruses have been coevolved with bats for a long time and the ancestors of SARS-CoV first infected the species of the genus Hipposideridae, subsequently spread to species of the Rhinolophidae and then to civets, and finally to humans.[34][35]
Alpaca coronavirus and human coronavirus 229E diverged before 1960.[36]
Human coronaviruses
Illustration of SARSr-CoV virion
Coronaviruses vary significantly in risk factor. Some can kill more than 30% of those infected (such as MERS-CoV), and some are relatively harmless, such as the common cold.[15] Coronaviruses cause colds with major symptoms, such as fever, and a sore throat from swollen adenoids, occurring primarily in the winter and early spring seasons.[37] Coronaviruses can cause pneumonia (either direct viral pneumonia or secondary bacterial pneumonia) and bronchitis (either direct viral bronchitis or secondary bacterial bronchitis).[38] The human coronavirus discovered in 2003, SARS-CoV, which causes severe acute respiratory syndrome (SARS), has a unique pathogenesis because it causes both upper and lower respiratory tract infections.[38]
Six species of human coronaviruses are known, with one species subdivided into two different strains, making seven strains of human coronaviruses altogether. Four of these strains produce the generally mild symptoms of the common cold:
Human coronavirus OC43 (HCoV-OC43), of the genus β-CoV
Human coronavirus HKU1 (HCoV-HKU1), β-CoV, its genome has 75% similarity to OC43[39]
Human coronavirus 229E (HCoV-229E), α-CoV
Human coronavirus NL63 (HCoV-NL63), α-CoV
Three strains (two species) produce symptoms that are potentially severe; all three of these are β-CoV strains:
Middle East respiratory syndrome-related coronavirus (MERS-CoV)
Severe acute respiratory syndrome coronavirus (SARS-CoV)
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)
The coronaviruses HCoV-229E, -NL63, -OC43, and -HKU1 continually circulate in the human population and cause respiratory infections in adults and children worldwide.[40]
Outbreaks of coronavirus diseases
Severe acute respiratory syndrome (SARS)
Main article: Severe acute respiratory syndrome
Characteristics of human coronavirus strains
MERS-CoV, SARS-CoV, SARS-CoV-2,
and related diseases
MERS-CoVSARS-CoVSARS-CoV-2
DiseaseMERSSARSCOVID-19
Outbreaks2012, 2015,
20182002–20042019–2020
pandemic
Epidemiology
Date of first
identified caseJune
2012November
2002December
2019[41]
Location of first
identified caseJeddah,
Saudi ArabiaShunde,
ChinaWuhan,
China
Age average5644[42][a]56[43]
Sex ratio3.3:10.8:1[44]1.6:1[43]
Confirmed cases24948096[45]1,601,018[46][b]
Deaths858774[45]95,718[46][b]
Case fatality rate37%9.2%6.0%[46]
Symptoms
Fever98%99–100%87.9%[47]
Dry cough47%29–75%67.7%[47]
Dyspnea72%40–42%18.6%[47]
Diarrhea26%20–25%3.7%[47]
Sore throat21%13–25%13.9%[47]
Ventilatory support24.5%[48]14–20%4.1%[49]
Notes
^ Based on data from Hong Kong.
^ Jump up to: a b Data as of 10 April 2020.
vte
In 2003, following the outbreak of severe acute respiratory syndrome (SARS) which had begun the prior year in Asia, and secondary cases elsewhere in the world, the World Health Organization (WHO) issued a press release stating that a novel coronavirus identified by a number of laboratories was the causative agent for SARS. The virus was officially named the SARS coronavirus (SARS-CoV). More than 8,000 people were infected, about ten percent of whom died.[25]
Middle East respiratory syndrome (MERS)
Main article: Middle East respiratory syndrome
In September 2012, a new type of coronavirus was identified, initially called Novel Coronavirus 2012, and now officially named Middle East respiratory syndrome coronavirus (MERS-CoV).[50][51] The World Health Organization issued a global alert soon after.[52] The WHO update on 28 September 2012 said the virus did not seem to pass easily from person to person.[53] However, on 12 May 2013, a case of human-to-human transmission in France was confirmed by the French Ministry of Social Affairs and Health.[54] In addition, cases of human-to-human transmission were reported by the Ministry of Health in Tunisia. Two confirmed cases involved people who seemed to have caught the disease from their late father, who became ill after a visit to Qatar and Saudi Arabia. Despite this, it appears the virus had trouble spreading from human to human, as most individuals who are infected do not transmit the virus.[55] By 30 October 2013, there were 124 cases and 52 deaths in Saudi Arabia.[56]
After the Dutch Erasmus Medical Centre sequenced the virus, the virus was given a new name, Human Coronavirus—Erasmus Medical Centre (HCoV-EMC). The final name for the virus is Middle East respiratory syndrome coronavirus (MERS-CoV). The only U.S. cases (both survived) were recorded in May 2014.[57]
In May 2015, an outbreak of MERS-CoV occurred in the Republic of Korea, when a man who had traveled to the Middle East, visited four hospitals in the Seoul area to treat his illness. This caused one of the largest outbreaks of MERS-CoV outside the Middle East.[58] As of December 2019, 2,468 cases of MERS-CoV infection had been confirmed by laboratory tests, 851 of which were fatal, a mortality rate of approximately 34.5%.[59]
Coronavirus disease 2019 (COVID-19)
Main article: Coronavirus disease 2019
In December 2019, a pneumonia outbreak was reported in Wuhan, China.[60] On 31 December 2019, the outbreak was traced to a novel strain of coronavirus,[61] which was given the interim name 2019-nCoV by the World Health Organization (WHO),[62][63][64] later renamed SARS-CoV-2 by the International Committee on Taxonomy of Viruses. Some researchers have suggested the Huanan Seafood Wholesale Market may not be the original source of viral transmission to humans.[65][66]
As of 10 April 2020, there have been at least 95,718[46] confirmed deaths and more than 1,601,018[46] confirmed cases in the coronavirus pneumonia pandemic. The Wuhan strain has been identified as a new strain of Betacoronavirus from group 2B with approximately 70% genetic similarity to the SARS-CoV.[67] The virus has a 96% similarity to a bat coronavirus, so it is widely suspected to originate from bats as well.[65][68] The pandemic has resulted in travel restrictions and nationwide lockdowns in several countries.
Other animals
Coronaviruses have been recognized as causing pathological conditions in veterinary medicine since the 1930s.[9] Except for avian infectious bronchitis, the major related diseases have mainly an intestinal location.[69]
Diseases caused
Coronaviruses primarily infect the upper respiratory and gastrointestinal tract of mammals and birds. They also cause a range of diseases in farm animals and domesticated pets, some of which can be serious and are a threat to the farming industry. In chickens, the infectious bronchitis virus (IBV), a coronavirus, targets not only the respiratory tract but also the urogenital tract. The virus can spread to different organs throughout the chicken.[70] Economically significant coronaviruses of farm animals include porcine coronavirus (transmissible gastroenteritis coronavirus, TGE) and bovine coronavirus, which both result in diarrhea in young animals. Feline coronavirus: two forms, feline enteric coronavirus is a pathogen of minor clinical significance, but spontaneous mutation of this virus can result in feline infectious peritonitis (FIP), a disease associated with high mortality. Similarly, there are two types of coronavirus that infect ferrets: Ferret enteric coronavirus causes a gastrointestinal syndrome known as epizootic catarrhal enteritis (ECE), and a more lethal systemic version of the virus (like FIP in cats) known as ferret systemic coronavirus (FSC).[71] There are two types of canine coronavirus (CCoV), one that causes mild gastrointestinal disease and one that has been found to cause respiratory disease. Mouse hepatitis virus (MHV) is a coronavirus that causes an epidemic murine illness with high mortality, especially among colonies of laboratory mice.[72] Sialodacryoadenitis virus (SDAV) is highly infectious coronavirus of laboratory rats, which can be transmitted between individuals by direct contact and indirectly by aerosol. Acute infections have high morbidity and tropism for the salivary, lachrymal and harderian glands.[73]
A HKU2-related bat coronavirus called swine acute diarrhea syndrome coronavirus (SADS-CoV) causes diarrhea in pigs.[74]
Prior to the discovery of SARS-CoV, MHV had been the best-studied coronavirus both in vivo and in vitro as well as at the molecular level. Some strains of MHV cause a progressive demyelinating encephalitis in mice which has been used as a murine model for multiple sclerosis. Significant research efforts have been focused on elucidating the viral pathogenesis of these animal coronaviruses, especially by virologists interested in veterinary and zoonotic diseases.[75]
Domestic animals
Infectious bronchitis virus (IBV) causes avian infectious bronchitis.
Porcine coronavirus (transmissible gastroenteritis coronavirus of pigs, TGEV).[76][77]
Bovine coronavirus (BCV), responsible for severe profuse enteritis in of young calves.
Feline coronavirus (FCoV) causes mild enteritis in cats as well as severe Feline infectious peritonitis (other variants of the same virus).
the two types of canine coronavirus (CCoV) (one causing enteritis, the other found in respiratory diseases).
Turkey coronavirus (TCV) causes enteritis in turkeys.
Ferret enteric coronavirus causes epizootic catarrhal enteritis in ferrets.
Ferret systemic coronavirus causes FIP-like systemic syndrome in ferrets.[78]
Pantropic canine coronavirus.
Rabbit enteric coronavirus causes acute gastrointestinal disease and diarrhea in young European rabbits. Mortality rates are high.[79]
Porcine epidemic diarrhea virus (PED or PEDV), has emerged around the world.[80]
Genomic cis-acting elements
In common with the genomes of all other RNA viruses, coronavirus genomes contain cis-acting RNA elements that ensure the specific replication of viral RNA by a virally encoded RNA-dependent RNA polymerase. The embedded cis-acting elements devoted to coronavirus replication constitute a small fraction of the total genome, but this is presumed to be a reflection of the fact that coronaviruses have the largest genomes of all RNA viruses. The boundaries of cis-acting elements essential to replication are fairly well-defined, and the RNA secondary structures of these regions are understood. However, how these cis-acting structures and sequences interact with the viral replicase and host cell components to allow RNA synthesis is not well understood.[81][5]
Genome packaging
The assembly of infectious coronavirus particles requires the selection of viral genomic RNA from a cellular pool that contains an abundant excess of non-viral and viral RNAs. Among the seven to ten specific viral mRNAs synthesized in virus-infected cells, only the full-length genomic RNA is packaged efficiently into coronavirus particles. Studies have revealed cis-acting elements and trans-acting viral factors involved in the coronavirus genome encapsidation and packaging. Understanding the molecular mechanisms of genome selection and packaging is critical for developing antiviral strategies and viral expression vectors based on the coronavirus genome.[81][5]
A missing filter... Picture or maybe in the air of the time that brews a little anguish, it grinds ideas by dint of filtering the words... the cunning life with a twist. Angel or mill?
The COVID-19 pandemic has resulted in conspiracy theories and misinformation about the scale of the pandemic and the origin, prevention, diagnosis, and treatment of the disease.[1][2][3] False information, including intentional disinformation, has been spread through social media,[2][4] text messages,[5] and mass media,[6] including the tabloid media,[7] conservative media,[8][9] state media of countries such as China,[10][11] Russia,[12][13] Iran,[14] and Turkmenistan.[2][15] It has also been spread by state-backed covert operations to generate panic and sow distrust in other countries.[16][17]
Misinformation has been propagated by celebrities, politicians[18][19] (including heads of state in countries such as the United States,[20][21] Iran,[22] and Brazil[23]), and other prominent public figures.[24] Commercial scams have claimed to offer at-home tests, supposed preventives, and "miracle" cures.[25][26] Politicians and leaders of some countries have promoted purported cures, while some religious groups said that the faith of their followers and God will protect them from the virus.[27][28][29] Others have claimed the virus is a lab-developed bio-weapon that was accidentally leaked,[30][31] or deliberately designed to target a country,[32] or one with a patented vaccine, a population control scheme, the result of a spy operation,[3][4] or linked to 5G networks.[33]
The World Health Organization has declared an "infodemic" of incorrect information about the virus, which poses risks to global health.[2]
Types and origin and effect
On January 30, the BBC reported about the increasing spread of conspiracy theories and false health advice in relation to COVID-19. Notable examples at the time included false health advice shared on social media and private chats, as well as conspiracy theories such as the origin in bat soup and the outbreak being planned with the participation of the Pirbright Institute.[1][34] On January 31, The Guardian listed seven instances of misinformation, adding the conspiracy theories about bioweapons and the link to 5G technology, and including varied false health advice.[35]
In an attempt to speed up research sharing, many researches have turned to preprint servers such as arXiv, bioRxiv, medRxiv or SSRN. Papers can be uploaded to these servers without peer review or any other editorial process that ensures research quality. Some of these papers have contributed to the spread of conspiracy theories. The most notable case was a preprint paper uploaded to bioRxiv which claimed that the virus contained HIV "insertions". Following the controversy, the paper was withdrawn.[36][37][38]
According to a study published by the Reuters Institute for the Study of Journalism, most misinformation related to COVID-19 involves "various forms of reconfiguration, where existing and often true information is spun, twisted, recontextualised, or reworked". While less misinformation "was completely fabricated". The study found no deep fakes in the studied sample. The study also found that "top-down misinformation from politicians, celebrities, and other prominent public figures", while accounting for a minority of the samples, captured a majority of the social media engagement. According to their classification, the largest category of misinformation (39%) includes "misleading or false claims about the actions or policies of public authorities, including government and international bodies like the WHO or the UN".[39]
A natural experiment correlated coronavirus misinformation with increased infection and death; of two similar television news shows on the same network, one took coronavirus seriously about a month earlier than the other. People and groups exposed to the slow-response news show had higher infection and death rates.[40]
The misinformations have been used by politicians, interest groups, and state actors in many countries to scapegoat other countries for the mishandling of the domestic responses, as well as furthering political, financial agenda.[41][42][43]
Combative efforts
Further information: Impact of the 2019–20 coronavirus pandemic on journalism
File:ITU - AI for Good Webinar Series - COVID-19 Misinformation and Disinformation during COVID-19.webm
International Telecommunication Union
On February 2, the World Health Organization (WHO) described a "massive infodemic", citing an over-abundance of reported information, accurate and false, about the virus that "makes it hard for people to find trustworthy sources and reliable guidance when they need it". The WHO stated that the high demand for timely and trustworthy information has incentivised the creation of a direct WHO 24/7 myth-busting hotline where its communication and social media teams have been monitoring and responding to misinformation through its website and social media pages.[44][45][46] The WHO specifically debunked several claims as false, including the claim that a person can tell if they have the virus or not simply by holding their breath; the claim that drinking large amounts of water will protect against the virus; and the claim that gargling salt water prevents infection.[47]
In early February, Facebook, Twitter and Google said they were working with WHO to address "misinformation".[48] In a blogpost, Facebook stated they would remove content flagged by global health organizations and local authorities that violate its content policy on misinformation leading to "physical harm".[49] Facebook is also giving free advertising to WHO.[50] Nonetheless, a week after Trump's speculation that sunlight could kill the virus, the New York Times found "780 Facebook groups, 290 Facebook pages, nine Instagram accounts and thousands of tweets pushing UV light therapies," content which those companies declined to remove from their platforms.[51]
At the end of February, Amazon removed more than a million products claimed to cure or protect against coronavirus, and removed tens of thousands of listings for health products whose prices were "significantly higher than recent prices offered on or off Amazon", although numerous items were "still being sold at unusually high prices" as of February 28.[52]
Millions of instances of COVID-19 misinformation have occurred across a number of online platforms.[53] Other fake news researchers noted certain rumors started in China; many of them later spread to Korea and the United States, prompting several universities in Korea to start the multilingual Facts Before Rumors campaign to separate common claims seen online.[54][55][56][57]
The media has praised Wikipedia's coverage of COVID-19 and its combating the inclusion of misinformation through efforts led by the Wiki Project Med Foundation and the English-language Wikipedia's WikiProject Medicine, among other groups.[58][59][60]
Many local newspapers have been severely affected by losses in advertising revenues from coronavirus; journalists have been laid off, and some have closed altogether.[61]
Many newspapers with paywalls lowered them for some or all their coronavirus coverage.[62][63] Many scientific publishers made scientific papers related to the outbreak open access.[64]
The Turkish Interior Ministry has been arresting social media users whose posts were "targeting officials and spreading panic and fear by suggesting the virus had spread widely in Turkey and that officials had taken insufficient measures".[65] Iran's military said 3600 people have been arrested for "spreading rumors" about coronavirus in the country.[66] In Cambodia, some individuals who expressed concerns about the spread of COVID-19 have been arrested on fake news charges.[67][68] Algerian lawmakers passed a law criminalising "fake news" deemed harmful to "public order and state security".[69] In the Philippines,[70] China,[71] India,[72][73] Egypt,[74] Bangladesh,[75] Morocco,[76] Pakistan,[77] Saudi Arabia,[78] Oman,[79] Iran,[80] Vietnam, Laos,[81] Indonesia,[73] Mongolia,[73] Sri Lanka,[73] Kenya, South Africa,[82] Somalia,[83] Thailand,[84] Kazakhstan,[85] Azerbaijan,[86] Malaysia[87] and Hong Kong, people have been arrested for allegedly spreading false information about the coronavirus pandemic.[88][73] The United Arab Emirates have introduced criminal penalties for the spread of misinformation and rumours related to the outbreak.[89]
Conspiracy theories
Conspiracy theories have appeared both in social media and in mainstream news outlets, and are heavily influenced by geopolitics.[90]
Accidental leakage
Virologist and immunologist Vincent R. Racaniello said that "accident theories – and the lab-made theories before them – reflect a lack of understanding of the genetic make-up of Sars-CoV-2."[91]
A number of allegations have emerged supposing a link between the virus and Wuhan Institute of Virology (WIV); among these is that the virus was an accidental leakage from WIV.[92] In 2017, U.S. molecular biologist Richard H. Ebright expressed caution when the WIV was expanded to become mainland China's first biosafety level 4 (BSL-4) laboratory, noting previous escapes of the SARS virus at other Chinese laboratories.[93] While Ebright refuted several conspiracy theories regarding the WIV (e.g., bioweapons research, or that the virus was engineered), he told BBC China this did not represent the possibility that the virus can be "completely ruled out" from entering the population due to a laboratory accident.[92] Various researchers contacted by NPR concluded there was "virtually no chance" (in NPR's words) that the pandemic virus had accidentally escaped from a laboratory.[94] Disinformation researcher Nina Jankowicz from Wilson Center indicates the lab leakage claim entered mainstream media in United States during April, propagated by pro-Trump news outlet.[43]
On February 14, 2020, Chinese scientists explored the possibility of accidental leakage and published speculations on scientific social networking website ResearchGate. The paper was neither peer-reviewed nor presented any evidence for its claims.[95] On March 5, the author of paper told Wall Street Journal in an interview why he decided to withdrew the paper by the end of February, stating: "the speculation about the possible origins in the post was based on published papers and media, and was not supported by direct proofs."[96][97] Several newspapers have referenced the paper.[95] Scientific American reported that Shi Zhengli, the lead researcher at WIV, started investigation on mishandling of experimental materials in the lab records, especially during disposal. She also tried to cross-check the novel coronavirus genome with the genetic information of other bat coronaviruses her team had collected. The result showed none of the sequences matched those of the viruses her team had sampled from bat caves.[98]
In February, it was alleged that the first person infected may have been a researcher at the institute named Huang Yanling.[99] Rumours circulated on Chinese social media that the researcher had become infected and died, prompting a denial from WIV, saying she was a graduate student enrolled in the Institute until 2015 and is not the patient zero.[100][99] In April, the conspiracy theory started to circulate around on Youtube and got picked up by conservative media, National Review.[101][6]
The South China Morning Post (SCMP) reported that one of the WIV's lead researchers, Shi Zhengli, was the particular focus of personal attacks in Chinese social media alleging that her work on bat-based viruses was the source of the virus; this led Shi to post: "I swear with my life, [the virus] has nothing to do with the lab". When asked by the SCMP to comment on the attacks, Shi responded: "My time must be spent on more important matters".[102] Caixin reported Shi made further public statements against "perceived tinfoil-hat theories about the new virus's source", quoting her as saying: "The novel 2019 coronavirus is nature punishing the human race for keeping uncivilized living habits. I, Shi Zhengli, swear on my life that it has nothing to do with our laboratory".[103] Immunologist Vincent Racaniello stated that virus leaking theory "reflect a lack of understanding of the genetic make-up of Sars-CoV-2 and its relationship to the bat virus". He says the bat virus researched in the institution "would not have been able to infect humans—the human Sars-CoV-2 has additional changes that allows it to infect humans."[91]
On April 14, the U.S. Chairman of the Joint Chiefs of Staff, General Mark Milley, in response to questions about the virus being manufactured in a lab, said "... it's inconclusive, although the weight of evidence seems to indicate natural. But we don't know for certain."[104] On that same day, Washington Post columnist Josh Rogin detailed a leaked cable of a 2018 trip made to the WIV by scientists from the U.S. Embassy. The article was referenced and cited by conservative media to push the lab leakage theory.[43] Rogin's article went on to say that "What the U.S. officials learned during their visits concerned them so much that they dispatched two diplomatic cables categorized as Sensitive But Unclassified back to Washington. The cables warned about safety and management weaknesses at the WIV lab and proposed more attention and help. The first cable, which I obtained, also warns that the lab's work on bat coronaviruses and their potential human transmission represented a risk of a new SARS-like pandemic."[105] Rogin's article pointed out there was no evidence that the coronavirus was engineered, "But that is not the same as saying it didn't come from the lab, which spent years testing bat coronaviruses in animals."[105] The article went on to quote Xiao Qiang, a research scientist at the School of Information at the University of California, Berkeley, "I don't think it's a conspiracy theory. I think it's a legitimate question that needs to be investigated and answered. To understand exactly how this originated is critical knowledge for preventing this from happening in the future."[105] Washington Post's article and subsequent broadcasts drew criticism from virologist Angela Rasmussen of Columbia University, which she states "It's irresponsible for political reporters like Rogin [to] uncritically regurgitate a secret 'cable' without asking a single virologist or ecologist or making any attempt to understand the scientific context."[43] Rasmussen later compared biosafety procedure concerns to "having the health inspector come to your restaurant. It could just be, ‘Oh, you need to keep your chemical showers better stocked.’ It doesn’t suggest, however, that there are tremendous problems.”[106]
Days later, multiple media outlets confirmed that U.S. intelligence officials were investigating the possibility that the virus started in the WIV.[107][108][109][110] On April 23, Vox presented disputed arguments on lab leakage claims from several scientists.[111] Scientists suggested that virus samples cultured in the lab have significant amount of difference compare to SARS-CoV-2. The virus institution sampled RaTG13 in Yunnan, the closest known relative of the novel coronavirus with 96% shared genome. Edward Holmes, SARS-CoV-2 researcher at the University of Sydney, explained 4% of difference "is equivalent to an average of 50 years (and at least 20 years) of evolutionary change."[111][112] Virologist Peter Daszak, president of the EcoHealth Alliance, which studies emerging infectious diseases, noted the estimation that 1–7 million people in Southeast Asia who live or work in proximity to bats are infected each year with bat coronaviruses. In the interview with Vox, he comments, "There are probably half a dozen people that do work in those labs. So let's compare 1 million to 7 million people a year to half a dozen people; it's just not logical."[94][111]
On April 30, The New York Times reported the Trump administration demanded intelligence agencies to find evidence linking WIV with the origin of SARS-Cov-2. Secretary of State and former Central Intelligence Agency (C.I.A) director Mike Pompeo was reportedly leading the push on finding information regarding the virus origin. Analysts were concerned that pressure from senior officials could distort assessments from the intelligence community. Anthony Ruggiero, the head of the National Security Council which responsible for tracking weapons of mass destruction, expressed frustration during a video conference that C.I.A. was unable to form conclusive answer on the origin of the virus. According to current and former government officials, as of April 30, C.I.A has yet to gather any information beyond circumstantial evidence to bolster the lab theory.[113][114] US intelligence officers suggested that Chinese officials tried to conceal the severity of the outbreak in early days, but no evidence had shown China attempted to cover up a lab accident.[115] One day later, Trump claimed he has evidence of the lab theory, but offers no further details on it.[116][117] Jamie Metzl, a senior fellow at the Atlantic Council, claimed the SARS-CoV-2 virus "likely" came from a Wuhan virology testing laboratory, based on "circumstantial evidence". He was quoted as saying, "I have no definitive way of proving this thesis."[118]
On April 30, 2020, the U.S. intelligence and scientific communities issued a public statement dismissing the idea that the virus was not natural, while the investigation of the lab accident theory was ongoing.[119][120] The White House suggested an alternative explanation, along with a seemingly contradictory message, that the virus was man-made. In an interview with ABC News, Secretary of State Pompeo said he has no reason to disbelieve the intelligence community that the virus was natural. However, this contradicted the comment he made earlier in the same interview, in which he said "the best experts so far seem to think it was man-made. I have no reason to disbelieve that at this point."[121][122][123] On May 4, Australian tabloid The Daily Telegraph claimed a reportedly leaked dossier from Five Eyes, which alleged the probable outbreak was from the Wuhan lab.[124] Fox News and national security commentators in the US quickly followed up The Telegraph story,[125][126] rising the tension within international intelligence community.[127] Australian government, which is part of the Five Eyes nations, determined the leaked dossier was not a Five Eyes document, but a compilation of open-source materials that contained no information generated by intelligence gathering.[128] German intelligence community denied the claim of the leaked dossier, instead supported the probability of a natural cause.[129][130] Australian government sees the promotion of the lab theory from the United States counterproductive to Australia’s push for a more broad international-supported independent inquiry into the virus origins.[127] Senior officials in Australian government speculated the dossier was leaked by US embassy in Canberra to promote a narrative in Australia media that diverged from the mainstream belief of Australia.[127][128][125]
Beijing rejected the White House's claim, calling the claim "part of an election year strategy by President Donald Trump’s Republican Party".[131] Hua Chunying, Chinese Foreign Ministry spokeswoman, urged Mike Pompeo to present evidence for his claim. "Mr. Pompeo cannot present any evidence because he does not have any," Hua told a journalist during a regular briefing, "This matter should be handled by scientists and professionals instead of politicians out of their domestic political needs."[131][132] The Chinese ambassador, in an opinion published in the Washington Post, called on the White House to end the "blame game" over the coronavirus.[133][134] As of May 5, assessments and internal sources from the Five Eyes nations indicated that the coronavirus outbreak was the result of a laboratory accident was "highly unlikely", since the human infection was "highly likely" a result of natural human and animal interaction. However, to reach such a conclusion with total certainty would still require greater cooperation and transparency from the Chinese side.[135]
Anti-Israeli and antisemitic
Further information: Antisemitic canard
Iran's Press TV asserted that "Zionist elements developed a deadlier strain of coronavirus against Iran".[14] Similarly, various Arab media outlets accused Israel and the United States of creating and spreading COVID-19, avian flu, and SARS.[136] Users on social media offered a variety of theories, including the supposition that Jews had manufactured COVID-19 to precipitate a global stock market collapse and thereby profit via insider trading,[137] while a guest on Turkish television posited a more ambitious scenario in which Jews and Zionists had created COVID-19, avian flu, and Crimean–Congo hemorrhagic fever to "design the world, seize countries, [and] neuter the world's population".[138]
Israeli attempts to develop a COVID-19 vaccine prompted mixed reactions. Grand Ayatollah Naser Makarem Shirazi denied initial reports that he had ruled that a Zionist-made vaccine would be halal,[139] and one Press TV journalist tweeted that "I'd rather take my chances with the virus than consume an Israeli vaccine".[140] A columnist for the Turkish Yeni Akit asserted that such a vaccine could be a ruse to carry out mass sterilization.[141]
An alert by the U.S. Federal Bureau of Investigation regarding the possible threat of far-right extremists intentionally spreading the coronavirus mentioned blame being assigned to Jews and Jewish leaders for causing the pandemic and several statewide shutdowns.[142]
Anti-Muslim
Further information: 2020 Tablighi Jamaat coronavirus hotspot in Delhi
In India, Muslims have been blamed for spreading infection following the emergence of cases linked to a Tablighi Jamaat religious gathering.[143] There are reports of vilification of Muslims on social media and attacks on individuals in India.[144] Claims have been made Muslims are selling food contaminated with coronavirus and that a mosque in Patna was sheltering people from Italy and Iran.[145] These claims were shown to be false.[146] In the UK, there are reports of far-right groups blaming Muslims for the coronavirus outbreak and falsely claiming that mosques remained open after the national ban on large gatherings.[147]
Bioengineered virus
It has been repeatedly claimed that the virus was deliberately created by humans.
Nature Medicine published an article arguing against the conspiracy theory that the virus was created artificially. The high-affinity binding of its peplomers to human angiotensin-converting enzyme 2 (ACE2) was shown to be "most likely the result of natural selection on a human or human-like ACE2 that permits another optimal binding solution to arise".[148] In case of genetic manipulation, one of the several reverse-genetic systems for betacoronaviruses would probably have been used, while the genetic data irrefutably showed that the virus is not derived from a previously used virus template.[148] The overall molecular structure of the virus was found to be distinct from the known coronaviruses and most closely resembles that of viruses of bats and pangolins that were little studied and never known to harm humans.[149]
In February 2020, the Financial Times quoted virus expert and global co-lead coronavirus investigator Trevor Bedford: "There is no evidence whatsoever of genetic engineering that we can find", and "The evidence we have is that the mutations [in the virus] are completely consistent with natural evolution".[150] Bedford further explained, "The most likely scenario, based on genetic analysis, was that the virus was transmitted by a bat to another mammal between 20–70 years ago. This intermediary animal—not yet identified—passed it on to its first human host in the city of Wuhan in late November or early December 2019".[150]
On February 19, 2020, The Lancet published a letter of a group of scientists condemning "conspiracy theories suggesting that COVID-19 does not have a natural origin".[151]
Chinese biological weapon
India
Amidst a rise in Sinophobia, there have been conspiracy theories reported on India's social networks that the virus is "a bioweapon that went rogue" and also fake videos alleging that Chinese authorities are killing citizens to prevent its spread.[152]
Ukraine
According to the Kyiv Post, two common conspiracy theories online in Ukraine are that American author Dean Koontz predicted the pandemic in his 1981 novel The Eyes of Darkness, and that the coronavirus is a bioweapon leaked from a secret lab in Wuhan.[153]
United Kingdom
Tobias Ellwood said, "It would be irresponsible to suggest the source of this outbreak was an error in a Chinese military biological weapons programme ... But without greater Chinese transparency we cannot entirely completely sure."[154]
In February, Conservative MP Tobias Ellwood, chair of the Defence Select Committee of the UK House of Commons, publicly questioned the role of the Chinese Army's Wuhan Institute for Biological Products and called for the "greater transparency over the origins of the coronavirus".[154][non-primary source needed] The Daily Mail reported in early April 2020 that a member of COBRA (an ad-hoc government committee tasked with advising on crises[citation needed]) has stated while government intelligence does not dispute that the virus has a zoonotic origin, it also does not discount the idea of a leak from a Wuhan laboratory, saying "Perhaps it is no coincidence that there is that laboratory in Wuhan"; the Asia Times reported the story as if it were factual,[155] perhaps unaware of the reputation of the Daily Mail.
United States
Further information: Cyberwarfare in the United States and Propaganda in the United States
In January 2020, BBC News published an article about coronavirus misinformation, citing two January 24 articles from The Washington Times that said the virus was part of a Chinese biological weapons program, based at the Wuhan Institute of Virology (WIV).[1] The Washington Post later published an article debunking the conspiracy theory, citing U.S. experts who explained why the WIV was unsuitable for bioweapon research, that most countries had abandoned bioweapons as fruitless, and that there was no evidence the virus was genetically engineered.[156]
On January 29, financial news website and blog ZeroHedge suggested without evidence that a scientist at the WIV created the COVID-19 strain responsible for the coronavirus outbreak. Zerohedge listed the full contact details of the scientist supposedly responsible, a practice known as doxing, by including the scientist's name, photo, and phone number, suggesting to readers that they "pay [the Chinese scientist] a visit" if they wanted to know "what really caused the coronavirus pandemic".[157] Twitter later permanently suspended the blog's account for violating its platform-manipulation policy.[158]
Logo of the fictional Umbrella Corporation, which some internet rumours linked to the pandemic. The corporation was invented for the Resident Evil game series.
In January 2020, Buzzfeed News reported on an internet meme of a link between the logo of the WIV and "Umbrella Corporation", the agency that created the virus responsible for a zombie apocalypse in the Resident Evil franchise. Posts online noted that "Racoon [sic]" (the main city in Resident Evil) was an anagram of "Corona".[159] Snopes noted that the logo was not from the WIV, but a company named Shanghai Ruilan Bao Hu San Biotech Ltd (located some 500 miles (800 km) away in Shanghai), and that the correct name of the city in Resident Evil was "Raccoon City".[159]
In February 2020, U.S. Senator Tom Cotton (R-AR) suggested the virus may have originated in a Chinese bioweapon laboratory.[160] Francis Boyle, a law professor, also expressed support for the bioweapon theory suggesting it was the result of unintended leaks.[161] Cotton elaborated on Twitter that his opinion was only one of "at least four hypotheses". Multiple medical experts have indicated there is no evidence for these claims.[162] Conservative political commentator Rush Limbaugh said on The Rush Limbaugh Show—the most popular radio show in the U.S.—that the virus was probably "a ChiCom laboratory experiment" and the Chinese government was using the virus and the media hysteria surrounding it to bring down Donald Trump.[163][164]
On February 6, the White House asked scientists and medical researchers to rapidly investigate the origins of the virus both to address the current spread and "to inform future outbreak preparation and better understand animal/human and environmental transmission aspects of coronaviruses".[165] American magazine Foreign Policy said Xi Jinping's "political agenda may turn out to be a root cause of the epidemic" and that his Belt and Road Initiative has "made it possible for a local disease to become a global menace".[90]
The Inverse reported that "Christopher Bouzy, the founder of Bot Sentinel, conducted a Twitter analysis for Inverse and found [online] bots and trollbots are making an array of false claims. These bots are claiming China intentionally created the virus, that it's a biological weapon, that Democrats are overstating the threat to hurt Donald Trump and more. While we can't confirm the origin of these bots, they are decidedly pro-Trump."[166]
Conservative commentator Josh Bernstein claimed that the Democratic Party and the "medical deep state" were collaborating with the Chinese government to create and release the coronavirus to bring down Donald Trump. Bernstein went on to suggest those responsible should be locked in a room with infected coronavirus patients as punishment.[167][168]
Jerry Falwell Jr., the president of Liberty University, promoted a conspiracy theory on Fox News that North Korea and China conspired together to create the coronavirus.[169] He also said people were overreacting to the coronavirus outbreak and that Democrats were trying to use the situation to harm President Trump.[170]
Hospital ship attack
The hospital ship USNS Mercy (T-AH-19) deployed to the Port of Los Angeles to provide backup medical services for the region. On March 31, 2020, a Pacific Harbor Line freight train was deliberately derailed by its onboard engineer in an attempt to crash into the ship, but the attack was unsuccessful and no one was injured.[171][172] According to U.S. federal prosecutors, the train's engineer "[...] was suspicious of the Mercy, believing it had an alternate purpose related to COVID-19 or a government takeover".[173]
Population control scheme
See also: List of conspiracy theories § RFID chips
According to the BBC, Jordan Sather, a conspiracy theory YouTuber supporting the far-right QAnon conspiracy theory and the anti-vax movement, has falsely claimed the outbreak was a population control scheme created by Pirbright Institute in England and by former Microsoft CEO Bill Gates. This belief is held mostly by right-wing libertarians, NWO conspiracy theorists, and Christian Fundamentalists.[1][174]
Spy operation
Some people have alleged that the coronavirus was stolen from a Canadian virus research lab by Chinese scientists. Health Canada and the Public Health Agency of Canada said that conspiracy theory had "no factual basis".[175] The stories seem to have been derived[176] from a July 2019 news article[177] stating that some Chinese researchers had their security access to a Canadian Level 4 virology facility revoked in a federal police investigation; Canadian officials described this as an administrative matter and "there is absolutely no risk to the Canadian public."[177]
This article was published by the Canadian Broadcasting Corporation (CBC);[176] responding to the conspiracy theories, the CBC later stated that "CBC reporting never claimed the two scientists were spies, or that they brought any version of the coronavirus to the lab in Wuhan". While pathogen samples were transferred from the lab in Winnipeg, Canada to Beijing, China, on March 31, 2019, neither of the samples was a coronavirus, the Public Health Agency of Canada says the shipment conformed to all federal policies, and there has not been any statement that the researchers under investigation were responsible for sending the shipment. The current location of the researchers under investigation by the Royal Canadian Mounted Police is not being released.[175][178][179]
In the midst of the coronavirus epidemic, a senior research associate and expert in biological warfare with the Begin-Sadat Center for Strategic Studies, referring to a NATO press conference, identified suspicions of espionage as the reason behind the expulsions from the lab, but made no suggestion that coronavirus was taken from the Canadian lab or that it is the result of bioweapons defense research in China.[180]
U.S. biological weapon
Arab world
According to Washington DC-based nonprofit Middle East Media Research Institute, numerous writers in the Arabic press have promoted the conspiracy theory that COVID-19, as well as SARS and the swine flu virus, were deliberately created and spread to sell vaccines against these diseases, and it is "part of an economic and psychological war waged by the U.S. against China with the aim of weakening it and presenting it as a backward country and a source of diseases".[181] Iraqi political analyst Sabah Al-Akili on Al-Etejah TV, Saudi daily Al-Watan writer Sa'ud Al-Shehry, Syrian daily Al-Thawra columnist Hussein Saqer, and Egyptian journalist Ahmad Rif'at on Egyptian news website Vetogate, were some examples given by MEMRI as propagators of the U.S. biowarfare conspiracy theory in the Arabic world.[181]
China
Further information: Cyberwarfare by China, Propaganda in China, and Chinese information operations and information warfare
The Xinhua News Agency is among the news outlets that have published false information about COVID-19's origins.
According to London-based The Economist, plenty of conspiracy theories exist on China's internet about COVID-19 being the CIA's creation to keep China down.[182] NBC News however has noted that there have also been debunking efforts of U.S.-related conspiracy theories posted online, with a WeChat search of "Coronavirus is from the U.S." reported to mostly yield articles explaining why such claims are unreasonable.[183] According to an investigation by ProPublica, such conspiracy theories and disinformation have been propagated under the direction of China News Service, the country's second largest government-owned media outlet controlled by the United Front Work Department.[184] Global Times and Xinhua News Agency have similarly been implicated in propagating disinformation related to COVID-19's origins.[185][186]
Multiple conspiracy articles in Chinese from the SARS era resurfaced during the outbreak with altered details, claiming SARS is biological warfare. Some said BGI Group from China sold genetic information of the Chinese people to the U.S., which then specifically targeted the genome of Chinese individuals.[187]
On January 26, Chinese military enthusiast website Xilu published an article, claimed how the U.S. artificially combined the virus to "precisely target Chinese people".[188][189] The article was removed in early February. The article was further distorted on social media in Taiwan, which claimed "Top Chinese military website admitted novel coronavirus was Chinese-made bio-weapons".[190] Taiwan Fact-check center debunked the original article and its divergence, suggesting the original Xilu article distorted the conclusion from a legitimate research on Chinese scientific magazine Science China Life Sciences, which never mentioned the virus was engineered.[190] The fact-check center explained Xilu is a military enthusiastic tabloid established by a private company, thus it doesn't represent the voice of Chinese military.[190]
Some articles on popular sites in China have also cast suspicion on U.S. military athletes participating in the Wuhan 2019 Military World Games, which lasted until the end of October 2019, and have suggested they deployed the virus. They claim the inattentive attitude and disproportionately below-average results of American athletes in the games indicate they might have been there for other purposes and they might actually be bio-warfare operatives. Such posts stated that their place of residence during their stay in Wuhan was also close to the Huanan Seafood Wholesale Market, where the first known cluster of cases occurred.[191]
In March 2020, this conspiracy theory was endorsed by Zhao Lijian, a spokesperson from the Ministry of Foreign Affairs of the People's Republic of China.[192][193][194][195] On March 13, the U.S. government summoned Chinese Ambassador Cui Tiankai to Washington over the coronavirus conspiracy theory.[196] Over the next month, conspiracy theorists narrowed their focus to one U.S. Army Reservist, a woman who participated in the games in Wuhan as a cyclist, claiming she is "patient zero". According to a CNN report, these theories have been spread by George Webb, who has nearly 100,000 followers on YouTube, and have been amplified by a report by CPC-owned newspaper Global Times.[197][198]
Iran
Further information: Propaganda in Iran
Reza Malekzadeh, deputy health minister, rejected bioterrorism theories.
According to Radio Farda, Iranian cleric Seyyed Mohammad Saeedi accused U.S. President Donald Trump of targeting Qom with coronavirus "to damage its culture and honor". Saeedi claimed that Trump is fulfilling his promise to hit Iranian cultural sites, if Iranians took revenge for the airstrike that killed of Quds Force Commander Qasem Soleimani.[199]
Iranian TV personality Ali Akbar Raefipour claimed the coronavirus was part of a "hybrid warfare" programme waged by the United States on Iran and China.[200] Brigadier General Gholam Reza Jalali, head of Iranian Civil Defense Organization, claimed the coronavirus is likely a biological attack on China and Iran with economic goals.[201][202]
Hossein Salami, the head of Islamic Revolutionary Guard Corps (IRGC), claimed the coronavirus outbreak in Iran may be due to a U.S. "biological attack".[203] Several Iranian politicians, including Hossein Amir-Abdollahian, Rasoul Falahati, Alireza Panahian, Abolfazl Hasanbeigi and Gholamali Jafarzadeh Imanabadi, also made similar remarks.[204] Iranian Supreme Leader, the Ayatollah Ali Khamenei, made similar suggestions.[205]
Former Iranian president Mahmoud Ahmadinejad sent a letter to the United Nations on March 9, claiming that "it is clear to the world that the mutated coronavirus was produced in lab" and that COVID-19 is "a new weapon for establishing and/or maintaining political and economic upper hand in the global arena".[206]
The late[207] Ayatollah Hashem Bathaie Golpayegani claimed that "America is the source of coronavirus, because America went head to head with China and realised it cannot keep up with it economically or militarily."[208]
Reza Malekzadeh, Iran's deputy health minister and former Minister of Health, rejected claims that the virus was a biological weapon, pointing out that the U.S. would be suffering heavily from it. He said Iran was hard-hit because its close ties to China and reluctance to cut air ties introduced the virus, and because early cases had been mistaken for influenza.[205]
Philippines
In the Philippine Senate, Tito Sotto has promoted his belief that COVID-19 is a bioweapon.
A Filipino Senator, Tito Sotto, played a bioweapon conspiracy video in a February 2020 Senate hearing, suggesting the coronavirus is biowarfare waged against China.[209][210]
Russia
Further information: Cyberwarfare by Russia and Propaganda in the Russian Federation
On February 22, U.S. officials alleged that Russia is behind an ongoing disinformation campaign, using thousands of social media accounts on Twitter, Facebook and Instagram to deliberately promote unfounded conspiracy theories, claiming the virus is a biological weapon manufactured by the CIA and the U.S. is waging economic war on China using the virus.[211][12][212] The acting assistant secretary of state for Europe and Eurasia, Philip Reeker, said "Russia's intent is to sow discord and undermine U.S. institutions and alliances from within" and "by spreading disinformation about coronavirus, Russian malign actors are once again choosing to threaten public safety by distracting from the global health response."[211] Russia denies the allegation, saying "this is a deliberately false story".[213]
According to U.S.-based The National Interest magazine, although official Russian channels had been muted on pushing the U.S. biowarfare conspiracy theory, other Russian media elements do not share the Kremlin's restraint.[214] Zvezda, a news outlet funded by the Russian Defense Ministry, published an article titled "Coronavirus: American biological warfare against Russia and China", claiming that the virus is intended to damage the Chinese economy, weakening its hand in the next round of trade negotiations.[214] Ultra-nationalist politician and leader of the Liberal Democratic Party of Russia, Vladimir Zhirinovsky, claimed on a Moscow radio station that the virus was an experiment by the Pentagon and pharmaceutical companies. Politician Igor Nikulin made rounds on Russian television and news media, arguing that Wuhan was chosen for the attack because the presence of a BSL-4 virus lab provided a cover story for the Pentagon and CIA about a Chinese bio-experiment leak.[214] An EU-document claims 80 attempts by Russian media to spread disinformation related to the epidemic.[215]
According to the East StratCom Task Force, the Sputnik news agency was active publishing stories speculating that the virus could've been invented in Latvia, that it was used by Communist Party of China to curb protests in Hong Kong, that it was introduced intentionally to reduce the number of elder people in Italy, that it was targeted against the Yellow Vests movement, and making many other speculations. Sputnik branches in countries including Armenia, Belarus, Spain, and in the Middle East came up with versions of these stories.[216]
Venezuela
Constituent Assembly member Elvis Méndez declared that the coronavirus was a "bacteriological sickness created in '89, in '90 and historically" and that it was a sickness "inoculated by the gringos". Méndez theorized that the virus was a weapon against Latin America and China and that its purpose was "to demoralize the person, to weaken to install their system".[217]
COVID-19 recovery
It has been wrongly claimed that anyone infected with COVID-19 will have the virus in their bodies for life. While there is no curative treatment, infected individuals can recover from the disease, eliminating the virus from their bodies; getting supportive medical care early can help.[279]
COVID-19 xenophobic blaming by ethnicity and religion
Main article: List of incidents of xenophobia and racism related to the 2019–20 coronavirus pandemic
File:IOM - Fighting Stigma and Discrimination against Migrants during COVID-19.webm
UN video warns that misinformation against groups may lower testing rates and increase transmission.
COVID-19-related xenophobic attacks have been made against people the attacker blamed for COVID-19 on the basis of their ethnicity. People who are considered to look Chinese have been subjected to COVID-19-related verbal and physical attacks in many other countries, often by people accusing them of transmitting the virus.[281][282][283] Within China, there has been discrimination (such as evictions and non-service in shops) against people from anywhere closer to Wuhan (where the pandemic started) and against anyone perceived as being non-Chinese (especially those considered African), as the Chinese government has blamed continuing cases on re-introductions of the virus from abroad (90% of reintroduced cases were by Chinese passport-holders). Neighbouring countries have also discriminated against people seen as Westerners.[284][285][286] People have also simply blamed other local groups along the lines of pre-existing social tensions and divisions, sometimes citing reporting of COVID-19 cases within that group. For instance, Muslims have been widely blamed, shunned, and discriminated against in India (including some violent attacks), amid unfounded claims that Muslims are deliberately spreading COVID-19, and a Muslim event at which the disease did spread has received far more public attention than many similar events run by other groups and the government.[287] White supremacist groups have blamed COVID-19 on non-whites and advocated deliberately infecting minorities they dislike, such as Jews.[288]
False causes
5G
5G towers have been burned by people wrongly blaming them for COVID-19.
Openreach engineers appealed on anti-5G Facebook groups, saying they aren't involved in mobile networks, and workplace abuse is making it difficult for them to maintain phonelines and broadband.
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In February 2020 BBC News reported that conspiracy theorists on social media groups alleged a link between coronavirus and 5G mobile networks, claiming that Wuhan and Diamond Princess outbreaks were directly caused by electromagnetic fields and by the introduction of 5G and wireless technologies. Some conspiracy theorists also alleged that the coronavirus outbreak was a cover-up for a 5G-related illness.[33] In March 2020, Thomas Cowan, a holistic medical practitioner who trained as a physician and operates on probation with Medical Board of California, alleged that coronavirus is caused by 5G, based on the claims that African countries were not affected significantly by the pandemic and Africa was not a 5G region.[289][290] Cowan also falsely alleged that the viruses were wastes from cells that are poisoned by electromagnetic fields and historical viral pandemics coincided with the major developments in radio technology.[290] The video of his claims went viral and was recirculated by celebrities including Woody Harrelson, John Cusack, and singer Keri Hilson.[291] The claims may also have been recirculated by an alleged "coordinated disinformation campaign", similar to campaigns used by the Internet Research Agency in Saint Petersburg, Russia.[292] The claims were criticized on social media and debunked by Reuters,[293] USA Today,[294] Full Fact[295] and American Public Health Association executive director Georges C. Benjamin.[289][296]
Professor Steve Powis, national medical director of NHS England, described theories linking 5G mobile phone networks to COVID-19 as the "worst kind of fake news".[297] Viruses cannot be transmitted by radio waves. COVID-19 has spread and continues to spread in many countries that do not have 5G networks.[279]
After telecommunications masts in several parts of the United Kingdom were the subject of arson attacks, British Cabinet Office Minister Michael Gove said the theory that COVID-19 virus may be spread by 5G wireless communication is "just nonsense, dangerous nonsense as well".[298] Vodafone announced that two Vodafone masts and two it shares with O2 had been targeted.[299][300]
By Monday April 6, 2020 at least 20 mobile phone masts in the UK had been vandalised since the previous Thursday.[301] Because of slow rollout of 5G in the UK, many of the damaged masts had only 3G and 4G equipment.[301] Mobile phone and home broadband operators estimated there were at least 30 incidents of confronting engineers maintaining equipment in the week up to April 6.[301] There have been eleven incidents of attempted arson at mobile phone masts in the Netherlands, including one case where "Fuck 5G" was written, as well as in Ireland and Cyprus.[302][303] Facebook has deleted multiple messages encouraging attacks on 5G equipment.[301]
Engineers working for Openreach posted pleas on anti-5G Facebook groups asking to be spared abuse as they are not involved with maintaining mobile networks.[304] Mobile UK said the incidents were affecting attempts to maintain networks that support home working and provide critical connections to vulnerable customers, emergency services and hospitals.[304] A widely circulated video shows people working for broadband company Community Fibre being abused by a woman who accuses them of installing 5G as part of a plan to kill the population.[304]
YouTube announced that it would reduce the amount of content claiming links between 5G and coronavirus.[299] Videos that are conspiratorial about 5G that do not mention coronavirus would not be removed, though they might be considered "borderline content", removed from search recommendations and losing advertising revenue.[299] The discredited claims had been circulated by British conspiracy theorist David Icke in videos (subsequently removed) on YouTube and Vimeo, and an interview by London Live TV network, prompting calls for action by Ofcom.[305][306]
On April 13, 2020, Gardaí were investigating fires at 5G masts in County Donegal, Ireland.[307] Gardaí and fire services had attended the fires the previous night in an attempt to put them out.[307] Although Gardaí were awaiting results of tests they were treating the fires as deliberate.[307]
There were 20 suspected arson attacks on phone masts in the UK over the Easter 2020 weekend.[297] These included an incident in Dagenham where three men were arrested on suspicion of arson, a fire in Huddersfield that affected a mast used by emergency services and a fire in a mast that provides mobile connectivity to the NHS Nightingale Hospital Birmingham.[297]
Ofcom issued guidance to ITV following comments by Eamonn Holmes after comments made by Holmes about 5G and coronavirus on This Morning.[308] Ofcom said the comments were "ambiguous" and "ill-judged" and they "risked undermining viewers' trust in advice from public authorities and scientific evidence".[308] Ofcom also local channel London Live in breach of standards for an interview it had with David Icke who it said had " expressed views which had the potential to cause significant harm to viewers in London during the pandemic".[308]
Some telecoms engineers have reported threats of violence, including threats to stab and murder them, by individuals who believe them to be working on 5G networks.[309] West Midlands Police said the crimes in question are being taken very seriously.[309]
On April 24, 2020 The Guardian revealed that an evangelical pastor from Luton had provided the male voice on a recording blaming 5G for deaths caused by coronavirus.[310] Jonathon James claimed to have formerly headed the largest business-unit at Vodafone, but insiders at the company said that he was hired for a sales position in 2014 when 5G was not a priority for the company and that 5G would not have been part of his job.[310] He left the company after less than a year.[310]
Mosquitoes
It has been claimed that mosquitoes transmit coronavirus. There is no evidence that this is true; coronavirus spreads through small droplets of saliva and mucus.[279]
Petrol pumps
A warning claiming to be from the Australia Department of Health said coronavirus spreads through petrol pumps and that everyone should wear gloves when filling up petrol in their cars.[311]
Shoe-wearing
There were claims that wearing shoes at one's home was the reason behind the spread of the coronavirus in Italy.[312]
Resistance/susceptibility based on ethnicity
There have been claims that specific ethnicities are more or less vulnerable to COVID-19. COVID-19 is a new zoonotic disease, so no population has yet had the time to develop population immunity.[medical citation needed]
Beginning on February 11, reports, quickly spread via Facebook, implied that a Cameroonian student in China had been completely cured of the virus due to his African genetics. While a student was successfully treated, other media sources have noted that no evidence implies Africans are more resistant to the virus and labeled such claims as false information.[313] Kenyan Secretary of Health Mutahi Kagwe explicitly refuted rumors that "those with black skin cannot get coronavirus", while announcing Kenya's first case on March 13.[314] This myth was cited as a contributing factor in the disproportionately high rates of infection and death observed among African Americans.[315][316]
There have been claims of "Indian immunity": that the people of India have more immunity to the COVID-19 virus due to living conditions in India. This idea was deemed "absolute drivel" by Anand Krishnan, professor at the Centre for Community Medicine of the All India Institute of Medical Sciences (AIIMS). He said there was no population immunity to the COVID-19 virus yet, as it is new, and it is not even clear whether people who have recovered from COVID-19 will have lasting immunity, as this happens with some viruses but not with others.[317]
Iran's Supreme Leader Ayatollah Ali Khamenei claimed the virus was genetically targeted at Iranians by the U.S., and this is why it is seriously affecting Iran. He did not offer any evidence.[318][22]
Religious protection
A number of religious groups have claimed protection due to their faith, some refusing to stop large religious gatherings. In Israel, some Ultra-Orthodox Jews initially refused to close synagogues and religious seminaries and disregarded government restrictions because "The Torah protects and saves",[319] which resulted in an 8 times faster rate of infection among some groups.[320] The Tablighi Jamaat movement organised mass gatherings in Malaysia, India, and Pakistan whose participants believed that God will protect them resulted the biggest rise in COVID-19 cases in a number of countries.[321][29][322] In Iran, the head of Fatima Masumeh Shrine encouraged pilgrims to visit the shrine despite calls to close the shrine, saying that they "consider this holy shrine to be a place of healing."[323] In South Korea the River of Grace Community Church in Gyeonggi Province spread the virus after spraying salt water into their members' mouths in the belief that it would kill the virus,[324] while the Shincheonji Church of Jesus in Daegu where a church leader claimed that no Shincheonji worshipers had caught the virus in February while hundreds died in Wuhan later caused in the biggest spread of the virus in the country.[325][326]
In Somalia, myths have spread claiming Muslims are immune to the virus.[327]
Unproven protective and aggravating factors
Vegetarian immunity
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This section needs expansion. You can help by adding to it. (April 2020)
Claims that vegetarians are immune to coronavirus spread online in India, causing "#NoMeat_NoCoronaVirus" to trend on Twitter.[328][better source needed] Eating meat does not have an effect on COVID-19 spread, except for people near where animals are slaughtered, said Anand Krishnan.[329] Fisheries, Dairying and Animal Husbandry Minister Giriraj Singh said the rumour had significantly affected industry, with the price of a chicken falling to a third of pre-pandemic levels. He also described efforts to improve the hygiene of the meat supply chain.[330]
Efficacy of hand sanitiser, "antibacterial" soaps
Washing in soap and water for at least 20 seconds is the best way to clean hands. Second-best is a hand sanitizer that is at least 60% alcohol.[331]
Claims that hand sanitiser is merely "antibacterial not antiviral", and therefore ineffective against COVID-19, have spread widely on Twitter and other social networks. While the effectiveness of sanitiser depends on the specific ingredients, most hand sanitiser sold commercially inactivates SARS-CoV-2, which causes COVID-19.[332][333] Hand sanitizer is recommended against COVID-19,[279] though unlike soap, it is not effective against all types of germs.[334] Washing in soap and water for at least 20 seconds is recommended by the U.S. Centers for Disease Control (CDC) as the best way to clean hands in most situations. However, if soap and water are not available, a hand sanitizer that is at least 60% alcohol can be used instead, unless hands are visibly dirty or greasy.[331][335] The CDC and the Food and Drug Administration both recommend plain soap; there is no evidence that "antibacterial soaps" are any better, and limited evidence that they might be worse long-term.[336][337]
Alcohol (ethanol and poisonous methanol)
Contrary to some reports, drinking alcohol does not protect against COVID-19, and can increase health risks[279] (short term and long term). Drinking alcohol is ethanol; other alcohols, such as methanol, which causes methanol poisoning, are acutely poisonous, and may be present in badly-prepared alcoholic beverages.[338]
Iran has reported incidents of methanol poisoning, caused by the false belief that drinking alcohol would cure or protect against coronavirus;[339] alcohol is banned in Iran, and bootleg alcohol may contain methanol.[340] According to Iranian media in March 2020, nearly 300 people have died and more than a thousand have become ill due to methanol poisoning, while Associated Press gave figures of around 480 deaths with 2,850 others affected.[341] The number of deaths due to methanol poisoning in Iran reached over 700 by April.[342] Iranian social media had circulated a story from British tabloids that a British man and others had been cured of coronavirus with whiskey and honey,[339][343] which combined with the use of alcohol-based hand sanitizers as disinfectants, led to the false belief that drinking high-proof alcohol can kill the virus.[339][340][341]
Similar incidents have occurred in Turkey, with 30 Turkmenistan citizens dying from methanol poisoning related to coronavirus cure claims.[344][345]
In Kenya, the Governor of Nairobi Mike Sonko has come under scrutiny for including small bottles of the cognac Hennessy in care packages, falsely claiming that alcohol serves as "throat sanitizer" and that, from research, it is believed that "alcohol plays a major role in killing the coronavirus."[346][347]
Cocaine
Cocaine does not protect against COVID-19. Several viral tweets purporting that snorting cocaine would sterilize one's nostrils of the coronavirus spread around Europe and Africa. In response, the French Ministry of Health released a public service announcement debunking this claim, saying "No, cocaine does NOT protect against COVID-19. It is an addictive drug that causes serious side effects and is harmful to people's health." The World Health Organisation also debunked the claim.[348]
Ibuprofen
A tweet from French health minister Olivier Véran, a bulletin from the French health ministry, and a small speculative study in The Lancet Respiratory Medicine raised concerns about ibuprofen worsening COVID-19, which spread extensively on social media. The European Medicines Agency[349] and the World Health Organization recommended COVID-19 patients keep taking ibuprofen as directed, citing lack of convincing evidence of any danger.[350]
Helicopter spraying
In some Asian countries, it has been claimed that one should stay at home on particular days when helicopters spray disinfectant over homes for killing off COVID-19; no such spraying is taking place.[351][352]
Cruise ships safety from infection
Main article: COVID-19 pandemic on cruise ships
Claims by cruise-ship operators notwithstanding, there are many cases of coronaviruses in hot climates; some countries in the Caribbean, the Mediterranean, and the Persian Gulf are severely affected.
In March 2020, the Miami New Times reported that managers at Norwegian Cruise Line had prepared a set of responses intended to convince wary customers to book cruises, including "blatantly false" claims that the coronavirus "can only survive in cold temperatures, so the Caribbean is a fantastic choice for your next cruise", that "[s]cientists and medical professionals have confirmed that the warm weather of the spring will be the end of the [c]oronavirus", and that the virus "cannot live in the amazingly warm and tropical temperatures that your cruise will be sailing to".[353]
Flu is seasonal (becoming less frequent in the summer) in some countries, but not in others. While it is possible that the COVID-19 coronavirus will also show some seasonality, it is not yet known.[354][355][356][medical citation needed] The COVID-19 coronavirus spread along international air travel routes, including to tropical locations.[357] Outbreaks on cruise ships, where an older population lives in close quarters, frequently touching surfaces which others have touched, were common.[358][359]
It seems that COVID-19 can be transmitted in all climates.[279] It has seriously affected many warm-climate countries. For instance, Dubai, with an year-round average daily high of 28.0 Celsius (82.3°F) and the airport said to have the world's most international traffic, has had thousands of cases.
Vaccine pre-existence
It was reported that multiple social media posts have promoted a conspiracy theory claiming the virus was known and that a vaccine was already available. PolitiFact and FactCheck.org noted that no vaccine currently exists for COVID-19. The patents cited by various social media posts reference existing patents for genetic sequences and vaccines for other strains of coronavirus such as the SARS coronavirus.[360][4] The WHO reported as of February 5, 2020, that amid news reports of "breakthrough" drugs being discovered to treat people infected with the virus, there were no known effective treatments;[361] this included antibiotics and herbal remedies not being useful.[362] Scientists are working to develop a vaccine, but as of March 18, 2020, no vaccine candidates have completed Phase II clinical trials.[citation needed]
Miscellaneous
Name of the disease
Social media posts and internet memes claimed that COVID-19 means "Chinese Originated Viral Infectious Disease 19", or similar, as supposedly the "19th virus to come out of China".[477] In fact, the WHO named the disease as follows: CO stands for corona, VI for virus, D for disease and 19 for when the outbreak was first identified (31 December 2019).[478]
Bat soup
Some media outlets, including Daily Mail and RT, as well as individuals, disseminated a video showing a Chinese woman eating a bat, falsely suggesting it was filmed in Wuhan and connecting it to the outbreak.[479][480] However, the widely circulated video contains unrelated footage of a Chinese travel vlogger, Wang Mengyun, eating bat soup in the island country of Palau in 2016.[479][480][481][482] Wang posted an apology on Weibo,[481][482] in which she said she had been abused and threatened,[481] and that she had only wanted to showcase Palauan cuisine.[481][482] The spread of misinformation about bat consumption has been characterized by xenophobic and racist sentiment toward Asians.[90][483][484] In contrast, scientists suggest the virus originated in bats and migrated into an intermediary host animal before infecting people.[90][485]
en.wikipedia.org/wiki/Misinformation_related_to_the_COVID...
Although sunlight can help kill coronaviruses on surfaces, it doesn’t work fast enough said Andrea Armani, a professor of chemical engineering and materials science at USC.
“
A coronavirus’ outer layer weakens as the temperature rises, Armani said. So when ultraviolet light from the sun heats up surfaces where the virus lands, its survival period will be somewhat shorter. (How much shorter depends on multiple factors, she added.)
But the sun won’t make much difference in spots where shade or clouds reduce the optical intensity of sunlight. Nor will sunshine prevent the virus from spreading from person to person through droplets of saliva or mucus in the air.
Karin Michels, chair of the epidemiology department at UCLA’s Fielding School of Public Health, said there was “no good data” to support the idea that the UV in sunlight would make any difference in the coronavirus infection rate.
The risk, she said, depends more on how many people show up to the beach and whether they can practice proper physical distancing.
Aunque la luz solar puede ayudar a matar los coronavirus en las superficies, no funciona lo suficientemente rápido, dijo Andrea Armani, profesora de ingeniería química y ciencia de los materiales en la USC.
"La capa externa de un coronavirus se debilita a medida que aumenta la temperatura, dijo Armani. Entonces, cuando la luz ultravioleta del sol calienta las superficies donde aterriza el virus, su período de supervivencia será algo más corto. (Cuánto más corto depende de múltiples factores, agregó).
Pero el sol no hará mucha diferencia en los lugares donde la sombra o las nubes reducen la intensidad óptica de la luz solar. La luz del sol tampoco impedirá que el virus se propague de persona a persona a través de gotas de saliva o moco en el aire.
Karin Michels, presidenta del departamento de epidemiología de la Fielding School of Public Health de la UCLA, dijo que "no había buenos datos" para respaldar la idea de que los rayos UV en la luz solar harían alguna diferencia en la tasa de infección por coronavirus.
El riesgo, dijo, depende más de cuántas personas se presenten en la playa y de si pueden practicar el distanciamiento físico adecuado.
he 2019–20 coronavirus pandemic is an ongoing pandemic of coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).The outbreak started in Wuhan, Hubei province, China, in December 2019. The World Health Organization (WHO) declared the outbreak to be a Public Health Emergency of International Concern on 30 January 2020 and recognized it as a pandemic on 11 March 2020. As of 4 April 2020, more than 1.18 million cases of COVID-19 have been reported in more than 200 countries and territories,[5] resulting in more than 63,900 deaths. More than 244,000 people have recovered. The virus is mainly spread during close contact,[c] and by small droplets produced during coughing,[d] sneezing, or talking. These small droplets may also be produced during breathing, but rapidly fall to the ground or surfaces and are not generally spread through the air over large distances.People may also catch COVID-19 by touching a contaminated surface and then their face. The virus can survive on surfaces up to 72 hours. It is most contagious during the first 3 days after symptom onset, although spread may be possible before symptoms appear and in later stages of the disease. The time between exposure and symptom onset is typically around five days, but may range from 2 to 14 days. Common symptoms include fever, cough, and shortness of breath.Complications may include pneumonia and acute respiratory distress syndrome. There is no known vaccine or specific antiviral treatment.Primary treatment is symptomatic and supportive therapy. Recommended preventive measures include hand washing, covering one's mouth when coughing, maintaining distance from other people, and monitoring and self-isolation for people who suspect they are infected. Efforts to prevent the virus spread include travel restrictions, quarantines, curfews, workplace hazard controls, event postponements and cancellations, and facility closures. These include national or regional quarantines throughout the world (starting with the quarantine of Hubei), curfew measures in mainland China and South Korea, various border closures or incoming passenger restrictions,screening at airports and train stations, and outgoing passenger travel bans. The pandemic has led to severe global socioeconomic disruption, the postponement or cancellation of sporting, religious, and cultural events, and widespread fears of supply shortages resulting in panic buying.Schools and universities have closed either on a nationwide or local basis in more than 160 countries, affecting nearly 90 percent of the world's student population. Misinformation about the virus has spread online, and there have been incidents of xenophobia and discrimination against Chinese people and people of East and Southeast Asian descent and appearance, as well as against people from emergent hotspots around the globe. Health authorities in Wuhan, the capital of Hubei province, China, reported a cluster of pneumonia cases of unknown cause on 31 December 2019, and an investigation was launched in early January 2020. The cases mostly had links to the Huanan Seafood Wholesale Market and so the virus is thought to have a zoonotic origin. The virus that caused the outbreak is known as SARS-CoV-2, a newly discovered virus closely related to bat coronaviruses, pangolin coronaviruses, and SARS-CoV. The earliest known person with symptoms was later discovered to have fallen ill on 1 December 2019, and that person did not have visible connections with the later wet market cluster. Of the early cluster of cases reported in December 2019, two-thirds were found to have a link with the market.[314][315][316] On 13 March 2020, an unverified report from the South China Morning Post suggested that a case traced back to 17 November 2019, in a 55-year-old from Hubei province, may have been the first. On 26 February 2020, the WHO reported that, as new cases reportedly declined in China but suddenly increased in Italy, Iran, and South Korea, the number of new cases outside China had exceeded the number of new cases within China for the first time. There may be substantial underreporting of cases, particularly among those with milder symptoms. By 26 February, relatively few cases had been reported among youths, with those 19 and under making up 2.4% of cases worldwide. Government sources in Germany and the United Kingdom estimate that 60–70% of the population will need to become infected before effective herd immunity can be achieved. Cases refers to the number of people who have been tested for COVID-19, and whose test has been confirmed positive according to official protocols.[326] The number of people infected with COVID-19 will likely be much higher, as many of those with only mild or no symptoms may not have been tested. As of 23 March, no country had tested more than 3% of its population, and many countries have had official policies not to test those with only mild symptoms, such as Italy, the Netherlands, Spain, and Switzerland. The time from development of symptoms to death has been between 6 and 41 days, with the most common being 14 days.[18] As of 4 April 2020, approximately 63,900[4] deaths had been attributed to COVID-19. In China, as of 5 February about 80% of deaths were in those over 60, and 75% had pre-existing health conditions including cardiovascular diseases and diabetes. The first confirmed death was on 9 January 2020 in Wuhan. The first death outside mainland China occurred on 1 February in the Philippines, and the first death outside Asia was in France on 14 February. By 28 February, outside mainland China, more than a dozen deaths each were recorded in Iran, South Korea, and Italy. By 13 March, more than forty countries and territories had reported deaths, on every continent except Antarctica. Several measures are commonly used to quantify mortality. These numbers vary by region and over time, and are influenced by the volume of testing, healthcare system quality, treatment options, time since initial outbreak, and population characteristics such as age, sex, and overall health. The death-to-case ratio reflects the number of deaths divided by the number of diagnosed cases within a given time interval. Based on Johns Hopkins University statistics, the global death-to-case ratio is 5.4% (63,902/1,181,825) as of 4 April 2020.[4] The number varies by region. Other measures include the case fatality rate (CFR), which reflects the percent of diagnosed individuals who die from a disease, and the infection fatality rate (IFR), which reflects the percent of infected individuals (diagnosed and undiagnosed) who die from a disease. These statistics are not time bound and follow a specific population from infection through case resolution. A number of academics have attempted to calculate these numbers for specific populations. Some researchers have also attempted to estimate the IFR for the pandemic as a whole. In China, estimates for the "crude CFR", i.e. the death-to-case ratio decreased from 17.3% (for those with symptom onset 1–10 January 2020) to 0.7% (for those with symptom onset after 1 February 2020). The WHO asserts that the pandemic can be controlled. The peak and ultimate duration of the outbreak are uncertain and may differ by location. Maciej Boni of Penn State University stated, "Left unchecked, infectious outbreaks typically plateau and then start to decline when the disease runs out of available hosts. But it's almost impossible to make any sensible projection right now about when that will be". However, the Chinese government's senior medical adviser Zhong Nanshan argued that "it could be over by June" if all countries can be mobilized to follow the WHO's advice on measures to stop the spread of the virus. Adam Kucharski of the London School of Hygiene & Tropical Medicine stated that SARS-CoV-2 "is going to be circulating, potentially for a year or two".According to the Imperial College study led by Neil Ferguson, physical distancing and other measures will be required "until a vaccine becomes available (potentially 18 months or more)". William Schaffner of Vanderbilt University stated, "I think it's unlikely that this coronavirus—because it's so readily transmissible—will disappear completely" and it "might turn into a seasonal disease, making a comeback every year". The virulence of the comeback would depend on herd immunity and the extent of mutation. Symptoms of COVID-19 can be relatively non-specific and infected people may be asymptomatic. The two most common symptoms are fever (88%) and dry cough (68%). Less common symptoms include fatigue, respiratory sputum production (phlegm), loss of the sense of smell, shortness of breath, muscle and joint pain, sore throat, headache, chills, vomiting, hemoptysis, diarrhea, or cyanosis. The WHO states that approximately one person in six becomes seriously ill and has difficulty breathing.[357] The U.S. Centers for Disease Control and Prevention (CDC) lists emergency symptoms as difficulty breathing, persistent chest pain or pressure, sudden confusion, difficulty waking, and bluish face or lips; immediate medical attention is advised if these symptoms are present. Further development of the disease can lead to severe pneumonia, acute respiratory distress syndrome, sepsis, septic shock and death. Some of those infected may be asymptomatic, with no clinical symptoms but test results that confirm infection, so researchers have issued advice that those with close contact to confirmed infected people should be closely monitored and examined to rule out infection.Chinese estimates of the asymptomatic ratio range from few to 44%. The usual incubation period (the time between infection and symptom onset) ranges from one to 14 days; it is most commonly five days. As an example of uncertainty, estimates of loss of smell for people with COVID-19 were 30%, and then estimates fell to 15%. Some details about how the disease is spread are still being determined. The disease is believed to be primarily spread during close contact and by small droplets produced during coughing, sneezing, or talking;[9][10][12] with close contact being within 1 to 2 metres (3 to 6 feet). Studies have found that an uncovered coughing can lead to droplets travelling up to 4.5 metres (15 feet) to 8.2 metres (27 feet). Respiratory droplets may also be produced during breathing out, including when talking, though the virus is not generally airborne. The droplets can land in the mouths or noses of people who are nearby or possibly be inhaled into the lungs.[369] Some medical procedures such as intubation and cardiopulmonary resuscitation (CPR) may cause respiratory secretions to be aerosolized and thus result in airborne spread. It may also spread when one touches a contaminated surface and then touches their eyes, nose, or mouth.[9] While there are concerns it may spread by feces, this risk is believed to be low.[9][10] The Government of China denied the possibility of fecal-oral transmission of SARS-CoV-2. The virus is most contagious during the first 3 days after onset of symptoms, although spread may be possible before symptoms appear and in later stages of the disease.People have tested positive for the disease up to 3 days before onset of symptoms suggesting transmission is possible before developing significant symptoms. Only few reports of laboratory-confirmed asymptomatic cases exist, but asymptomatic transmission has been identified by some countries during contact tracing investigations. The European Centre for Disease Prevention and Control (ECDC) states that while it is not entirely clear how easily the disease spreads, one person generally infects two to three others.The virus survives for hours to days on surfaces. Specifically, the virus was found to be detectable for up to three days on plastic and stainless steel, for one day on cardboard, and for up to four hours on copper. This, however, varies based on the humidity and temperature. However, pets or other livestock may test positive but can't pass on coronavirus to humans, as there were reported cases of infected pets such as a cat in Belgium and two dogs in Hong Kong. There have been reports were those diagnosed with coronavirus and seemingly recovered, have been readmitted to hospitals after testing positive for the virus a second time. These cases are believed to be worsening of a lingering infection rather than re-infection. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a novel severe acute respiratory syndrome coronavirus, first isolated from three people with pneumonia connected to the cluster of acute respiratory illness cases in Wuhan. All features of the novel SARS-CoV-2 virus occur in related coronaviruses in nature. Outside the human body, the virus is killed by household soap, which bursts its protective bubble. SARS-CoV-2 is closely related to the original SARS-CoV. It is thought to have a zoonotic origin. Genetic analysis has revealed that the coronavirus genetically clusters with the genus Betacoronavirus, in subgenus Sarbecovirus (lineage B) together with two bat-derived strains. It is 96% identical at the whole genome level to other bat coronavirus samples (BatCov RaTG13). In February 2020, Chinese researchers found that there is only one amino acid difference in certain parts of the genome sequences between the viruses from pangolins and those from humans, however, whole-genome comparison to date found at most 92% of genetic material shared between pangolin coronavirus and SARS-CoV-2, which is insufficient to prove pangolins to be the intermediate host. Infection by the virus can be provisionally diagnosed on the basis of symptoms, though confirmation is ultimately by reverse transcription polymerase chain reaction (rRT-PCR) of infected secretions or CT imaging. A study comparing PCR to CT in Wuhan has suggested that CT is significantly more sensitive than PCR, though less specific, with many of its imaging features overlapping with other pneumonias and disease processes. As of March 2020, the American College of Radiology recommends that "CT should not be used to screen for or as a first-line test to diagnose COVID-19". The WHO has published several RNA testing protocols for SARS-CoV-2, with the first issued on 17 January. Testing uses real-time reverse transcription polymerase chain reaction (rRT-PCR). The test can be done on respiratory or blood samples. Results are generally available within a few hours to days. A person is considered at risk if they have travelled to an area with ongoing community transmission within the previous 14 days, or have had close contact with an infected person. Common key indicators include fever, coughing, and shortness of breath. Other possible indicators include fatigue, myalgia, anorexia, sputum production, and sore throat. Characteristic imaging features on radiographs and computed tomography (CT) of people who are symptomatic include asymmetric peripheral ground glass opacities and absent pleural effusions. The Italian Radiological Society is compiling an international online database of imaging findings for confirmed cases. Due to overlap with other infections such as adenovirus, imaging without confirmation by PCR is of limited specificity in identifying COVID-19. However, a large study in China compared chest CT results to PCR and demonstrated that though imaging is less specific for the infection, it is faster and more sensitive, suggesting its consideration as a screening tool in epidemic areas.[395] Artificial intelligence-based convolutional neural networks have been developed to detect imaging features of the virus with both radiographs and CT. Strategies for preventing transmission of the disease include maintaining overall good personal hygiene, washing hands, avoiding touching the eyes, nose, or mouth with unwashed hands, and coughing or sneezing into a tissue and putting the tissue directly into a waste container. Those who may already have the infection have been advised to wear a surgical mask in public. Physical distancing measures are also recommended to prevent transmission. Many governments have restricted or advised against all non-essential travel to and from countries and areas affected by the outbreak. However, the virus has reached the stage of community spread in large parts of the world. This means that the virus is spreading within communities, and some community members don't know where or how they were infected. Health care providers taking care of someone who may be infected are recommended to use standard precautions, contact precautions, and eye protection.
Contact tracing is an important method for health authorities to determine the source of an infection and to prevent further transmission. Misconceptions are circulating about how to prevent infection; for example, rinsing the nose and gargling with mouthwash are not effective. There is no COVID-19 vaccine, though many organizations are working to develop one. Hand washing is recommended to prevent the spread of the disease. The CDC recommends that people wash hands often with soap and water for at least twenty seconds, especially after going to the toilet or when hands are visibly dirty; before eating; and after blowing one's nose, coughing, or sneezing. This is because outside the human body, the virus is killed by household soap, which bursts its protective bubble. CDC further recommended using an alcohol-based hand sanitizer with at least 60% alcohol by volume when soap and water are not readily available.[398] The WHO advises people to avoid touching the eyes, nose, or mouth with unwashed hands. Surfaces may be decontaminated with a number of solutions (within one minute of exposure to the disinfectant for a stainless steel surface), including 62–71% ethanol, 50–100% isopropanol, 0.1% sodium hypochlorite, 0.5% hydrogen peroxide, and 0.2–7.5% povidone-iodine. Other solutions, such as benzalkonium chloride and chrohexidine gluconate, are less effective. The CDC recommends that if a COVID case is suspected or confirmed at a facility such as an office or daycare, all areas such as offices, bathrooms, common areas, shared electronic equipment like tablets, touch screens, keyboards, remote controls, and ATM machines used by the ill persons, should be disinfected. Health organizations recommended that people cover their mouth and nose with a bent elbow or a tissue when coughing or sneezing, and disposing of any tissue immediately. Surgical masks are recommended for those who may be infected, as wearing a mask can limit the volume and travel distance of expiratory droplets dispersed when talking, sneezing, and coughing. The WHO has issued instructions on when and how to use masks. According to Stephen Griffin, a virologist at the University of Leeds, "Wearing a mask can reduce the propensity [of] people to touch their faces, which is a major source of infection without proper hand hygiene." Masks have also been recommended for use by those taking care of someone who may have the disease. The WHO has recommended the wearing of masks by healthy people only if they are at high risk, such as those who are caring for a person with COVID-19, although they also acknowledge that wearing masks may help people avoid touching their face. Several countries have started to encourage the use of face masks by members of the public. China has specifically recommended the use of disposable medical masks by healthy members of the public, particularly when coming into close contact (≤1 metre) with other people. Hong Kong recommends wearing a surgical mask when taking public transport or staying in crowded places. Thailand's health officials are encouraging people to make face masks at home out of cloth and wash them daily. The Czech Republic and Slovakia banned going out in public without wearing a mask or covering one's nose and mouth. The Austrian government mandated that everyone entering a grocery store must wear a face mask. Israel has asked all residents to wear face masks when in public. Taiwan, which has been producing ten million masks per day since mid-March, required passengers on trains and intercity buses to wear face masks on 1 April.Panama has asked its citizens to wear a face mask. Face masks have also been widely used in Japan, South Korea, Malaysia, and Singapore. Social distancing (also known as physical distancing) includes infection control actions intended to slow the spread of disease by minimizing close contact between individuals. Methods include quarantines; travel restrictions; and the closing of schools, workplaces, stadiums, theatres, or shopping centres. Individuals may apply social distancing methods by staying at home, limiting travel, avoiding crowded areas, using no-contact greetings, and physically distancing themselves from others. Many governments are now mandating or recommending social distancing in regions affected by the outbreak. The maximum gathering size recommended by government bodies and health organizations was swiftly reduced from 250 people (if there was no known COVID-19 spread in a region) to 50 people, and later to 10 people. On 22 March 2020, Germany banned public gatherings of more than two people. Older adults and those with underlying medical conditions such as diabetes, heart disease, respiratory disease, hypertension, and compromised immune systems face increased risk of serious illness and complications and have been advised by the CDC to stay home as much as possible in areas of community outbreak. In late March 2020, the WHO and other health bodies began to replace the use of the term "social distancing" with "physical distancing", to clarify that the aim is to reduce physical contact while maintaining social connections, either virtually or at a distance. The use of the term "social distancing" had led to implications that people should engage in complete social isolation, rather than encouraging them to stay in contact with others through alternative means. The government in Ireland released sexual health guidelines during the pandemic. These included recommendations to only have sex with someone you live with, who does not have the virus or symptoms of the virus. In late March 2020, it was reported that for more than 70 million people in India, who live in clustered slums and comprise of about one sixth of the total urban population, social distancing is not only physically impossible, but economically too. The reported reproduction rate of the COVID-19 disease could be 20% higher in Indian slums due to impenetrable living conditions, as compared to the global ratio, i.e. 2 to 3 percent.Self-isolation at home has been recommended for those diagnosed with COVID-19 and those who suspect they have been infected. Health agencies have issued detailed instructions for proper self-isolation. Many governments have mandated or recommended self-quarantine for entire populations living in affected areas.] The strongest self-quarantine instructions have been issued to those in high risk groups. Those who may have been exposed to someone with COVID-19 and those who have recently travelled to a country or region with widespread transmission have been advised to self-quarantine for 14 days from the time of last possible exposure.Strategies in the control of an outbreak are containment or suppression, and mitigation. Containment is undertaken in the early stages of the outbreak and aims to trace and isolate those infected as well as introduce other measures of infection control and vaccinations to stop the disease from spreading to the rest of the population. When it is no longer possible to contain the spread of the disease, efforts then move to the mitigation stage: measures are taken to slow the spread and mitigate its effects on the healthcare system and society. A combination of both containment and mitigation measures may be undertaken at the same time. Suppression requires more extreme measures so as to reverse the pandemic by reducing the basic reproduction number to less than 1. Part of managing an infectious disease outbreak is trying to decrease the epidemic peak, known as flattening the epidemic curve.[457] This decreases the risk of health services being overwhelmed and provides more time for vaccines and treatments to be developed. Non-pharmaceutical interventions that may manage the outbreak include personal preventive measures, such as hand hygiene, wearing face-masks, and self-quarantine; community measures aimed at physical distancing such as closing schools and cancelling mass gathering events; community engagement to encourage acceptance and participation in such interventions; as well as environmental measures such surface cleaning. More drastic actions aimed at containing the outbreak were taken in China once the severity of the outbreak became apparent, such as quarantining entire cities and imposing strict travel bans. Other countries also adopted a variety of measures aimed at limiting the spread of the virus. South Korea introduced mass screening and localized quarantines, and issued alerts on the movements of infected individuals. Singapore provided financial support for those infected who quarantined themselves and imposed large fines for those who failed to do so. Taiwan increased face mask production and penalized hoarding of medical supplies. Simulations for Great Britain and the United States show that mitigation (slowing but not stopping epidemic spread) and suppression (reversing epidemic growth) have major challenges. Optimal mitigation policies might reduce peak healthcare demand by 2/3 and deaths by half, but still result in hundreds of thousands of deaths and health systems being overwhelmed. Suppression can be preferred but needs to be maintained for as long as the virus is circulating in the human population (or until a vaccine becomes available, if that comes first), as transmission otherwise quickly rebounds when measures are relaxed. Long-term intervention to suppress the pandemic causes social and economic costs. There are no specific antiviral medications approved for COVID-19, but development efforts are underway, including testing of existing medications. Taking over-the-counter cold medications, drinking fluids, and resting may help alleviate symptoms. Depending on the severity, oxygen therapy, intravenous fluids, and breathing support may be required. The use of steroids may worsen outcomes.Several compounds that were previously approved for treatment of other viral diseases are being investigated for use in treating COVID-19. The World Health Organization also stated that some “traditional and home remedies” that can provide relief of the symptoms caused by SARS-CoV-19. Increasing capacity and adapting healthcare for the needs of COVID-19 patients is described by the WHO as a fundamental outbreak response measure.[469] The ECDC and the European regional office of the WHO have issued guidelines for hospitals and primary healthcare services for shifting of resources at multiple levels, including focusing laboratory services towards COVID-19 testing, cancelling elective procedures whenever possible, separating and isolating COVID-19 positive patients, and increasing intensive care capabilities by training personnel and increasing the number of available ventilators and beds.
3D print of a SARS-CoV-2—also known as 2019-nCoV, the virus that causes COVID-19—virus particle. The virus surface (blue) is covered with spike proteins (red) that enable the virus to enter and infect human cells. The spikes on the surface of coronaviruses give this virus family its name – corona, which is Latin for “crown,” and most any coronavirus will have a crown-like appearance.
Credit: NIH
Coronaviruses can result in severe illness for some
people in our communities.
Those who are at risk are an older adults
(increasing risk with each decade, especially over 60 years)
Contrary to the narrative that is being pushed by the mainstream that the COVID 19 virus was the result of a natural mutation and that it was transmitted to humans from bats via pangolins, Dr Luc Montagnier the man who discovered the HIV virus back in 1983 disagrees and is saying that the virus was man made.Professor Luc Montagnier, 2008 Nobel Prize winner for Medicine, claims that SARS-CoV-2 is a manipulated virus that was accidentally released from a laboratory in Wuhan, China. Chinese researchers are said to have used coronaviruses in their work to develop an AIDS vaccine. HIV DNA fragments are believed to have been found in the SARS-CoV-2 genome. We knew that the Chinese version of how the coronavirus emerged was increasingly under attack, but here’s a thesis that tells a completely different story about the Covid-19 pandemic, which is already responsible for more than 110,000 deaths worldwide. According to Professor Luc Montagnier, winner of the Nobel Prize for Medicine in 2008 for “discovering” HIV as the cause of the AIDS epidemic together with Françoise Barré-Sinoussi, the SARS-CoV-2 is a virus that was manipulated and accidentally released from a laboratory in Wuhan, China, in the last quarter of 2019. According to Professor Montagnier, this laboratory, known for its work on coronaviruses, tried to use one of these viruses as a vector for HIV in the search for an AIDS vaccine! “With my colleague, bio-mathematician Jean-Claude Perez, we carefully analyzed the description of the genome of this RNA virus,” explains Luc Montagnier, interviewed by Dr Jean-François Lemoine for the daily podcast at Pourquoi Docteur, adding that others have already explored this avenue: Indian researchers have already tried to publish the results of the analyses that showed that this coronavirus genome contained sequences of another virus, … the HIV virus (AIDS virus), but they were forced to withdraw their findings as the pressure from the mainstream was too great. To insert an HIV sequence into this genome requires molecular tools. In a challenging question Dr Jean-François Lemoine inferred that the coronavirus under investigation may have come from a patient who is otherwise infected with HIV. No, “says Luc Montagnier,” in order to insert an HIV sequence into this genome, molecular tools are needed, and that can only be done in a laboratory. According to the 2008 Nobel Prize for Medicine, a plausible explanation would be an accident in the Wuhan laboratory. He also added that the purpose of this work was the search for an AIDS vaccine. The truth will eventually come out In any case, this thesis, defended by Professor Luc Montagnier, has a positive turn. According to him, the altered elements of this virus are eliminated as it spreads: “Nature does not accept any molecular tinkering, it will eliminate these unnatural changes and even if nothing is done, things will get better, but unfortunately after many deaths.” Luc Montagnier added that with the help of interfering waves, we could eliminate these sequences and as a result stop the pandemic. This is enough to feed some heated debates! So much so that Professor Montagnier’s statements could also place him in the category of “conspiracy theorists”: “Conspirators are the opposite camp, hiding the truth,” he replies, without wanting to accuse anyone, but hoping that the Chinese will admit to what he believes happened in their laboratory.
www.pourquoidocteur.fr/Articles/Question-d-actu/32184-EXC...
To entice a confession from the Chinese he used the example of Iran which after taking full responsibility for accidentally hitting a Ukrainian plane was able to earn the respect of the global community. Hopefully the Chinese will do the right thing he ads. “In any case, the truth always comes out, it is up to the Chinese government to take responsibility.”
www.gilmorehealth.com/chinese-coronavirus-is-a-man-made-v...
Back in January, when the pandemic now consuming the world was still gathering force, a Berkeley research scientist named Xiao Qiang was monitoring China’s official statements about a new coronavirus then spreading through Wuhan and noticed something disturbing. Statements made by the World Health Organization, the international body that advises the world on handling health crises, often echoed China’s messages. “Particularly at the beginning, it was shocking when I again and again saw WHO’s [director-general], when he spoke to the press … almost directly quoting what I read on the Chinese government’s statements,” he told me.
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The most notorious example came in the form of a single tweet from the WHO account on January 14: “Preliminary investigations conducted by the Chinese authorities have found no clear evidence of human-to-human transmission of the novel #coronavirus.” That same day, the Wuhan Health Commission’s public bulletin declared, “We have not found proof for human-to-human transmission.” But by that point even the Chinese government was offering caveats not included in the WHO tweet. “The possibility of limited human-to-human transmission cannot be excluded,” the bulletin said, “but the risk of sustained transmission is low.”
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This, we now know, was catastrophically untrue, and in the months since, the global pandemic has put much of the world under an unprecedented lockdown and killed more than 100,000 people.
Read: The pandemic will cleave America in two
The U.S. was also slow to recognize the seriousness of this new coronavirus, which caught the entire country unprepared. President Donald Trump has blamed the catastrophe on any number of different actors, most recently, singling out the WHO. “They missed the call,” Trump said about the body at a briefing this week. “They could have called it months earlier.”
Trump may well be looking to deflect blame for his own missed calls, but inherent structural problems at the WHO do make the organization vulnerable to misinformation and political influence, especially at a moment when China has invested considerable resources cultivating influence in international organizations whose value the Trump administration has questioned. (Trump just in March announced he would nominate someone to fill the U.S. seat on the WHO’s Executive Board, which has been vacant since 2018.)
Even in January, when Chinese authorities were downplaying the extent of the virus, doctors at the epicenter of the outbreak in Wuhan reportedly observed human-to-human transmission, not least by contracting the disease themselves. In the most famous example, Dr. Li Wenliang was censured for “spreading rumors” after trying to alert other doctors of the new respiratory ailment; he later died of the virus himself at age 33. China now claims him as a martyr. Asked about Li’s case at a press conference, the executive director of the WHO’s Health Emergencies Programme, Michael Ryan, said, “We all mourn the loss of a fellow physician and colleague” but stopped short of condemning China for accusing him. “There is an understandable confusion that occurs at the beginning of an epidemic,” Ryan added. “So we need to be careful to label misunderstanding versus misinformation; there's a difference. People can misunderstand and they can overreact.”
Those lost early weeks also coincided with the Chinese New Year, for which millions of people travel to visit family and friends. “That’s when millions of Wuhan people were misinformed,” Xiao said. “Then they traveled all over China, all over the world.”
Read: China hawks are calling the coronavirus a ‘wake-up call’
The WHO, meanwhile, was getting its information from the same Chinese authorities who were misinforming their own public, and then offering it to the world with its own imprimatur. On January 20, a Chinese official confirmed publicly for the first time that the virus could indeed spread among humans, and within days locked down Wuhan. But by then it was too late.
It took another week for the WHO to declare the spread of the virus a global health emergency—during which time Dr. Tedros Adhanom Ghebreyesus, the WHO’s director-general, visited China and praised the country’s leadership for “setting a new standard for outbreak response.” Another month and a half went by before the WHO called COVID-19 a pandemic, at which point the virus had killed more than 4,000 people, and had infected 118,000 people across nearly every continent.
The organization’s detractors are now seizing on these missteps and delays to condemn the WHO (for which the U.S. is the largest donor), call for cutting the organization’s funding, or demand Tedros’s resignation. At the White House, Trump’s trade adviser Peter Navarro has been a sharp critic.
“Even as the WHO under Tedros refused to brand the outbreak as a pandemic for precious weeks and WHO officials repeatedly praised the [Chinese Communist Party] for what we now know was China’s coordinated effort to hide the dangers of the Wuhan virus from the world, the virus spread like wildfire, in no small part because thousands of Chinese citizens continued to travel around the world,” Navarro wrote to me in an email. Secretary of State Mike Pompeo recently said the administration was “reevaluating our funding with respect to the World Health Organization;” Trump has said an announcement on the matter will come next week. On the Hill, Republican Senators Martha McSally of Arizona and Rick Scott of Florida are both seeking an investigation of the WHO’s performance in the crisis and whether China somehow manipulated the organization. “Anybody who’s clear-eyed about it understands that Communist China has been covering up the realities of the coronavirus from Day 1,” McSally, who has called for Tedros to resign, told me. “We don’t expect the WHO to parrot that kind of propaganda.” Scott told me he wants to know whether the WHO followed their own procedures for handling a pandemic and why the organization hasn’t been forceful in condemning China’s missteps.
Asked for comment, a representative from the WHO pointed to a press conference Tedros gave this week. “Please quarantine politicizing COVID,” Tedros said then. “We will have many body bags in front of us if we don’t behave … The United States and China should come together and fight this dangerous enemy.” Even in early January, when it was still describing the disease as a mysterious new pneumonia, the WHO was publishing regular guidance for countries and health-care workers on how to mitigate its spread. And the organization says it has now shipped millions of pieces of protective gear to 75 countries, sent tests to more than 126, and offered training materials for health-care workers.
In any case, it’s not the WHO’s fault if China obscured the problem early on, says Charles Clift, a senior consulting fellow at Chatham House’s Center for Universal Health who worked at the WHO from 2004 to 2006. “We’d like more transparency, that’s true, but if countries find reasons to not be transparent, it’s difficult to know what we can do about it.” The organization’s major structural weakness is that it relies on information from its member countries—and the WHO team that visited China in February to evaluate the response did so jointly with China’s representatives. The resulting report did not mention delays in information-sharing, but did say that “China’s bold approach to contain the rapid spread of this new respiratory pathogen has changed the course of a rapidly escalating and deadly epidemic.” The mission came back telling reporters they were largely satisfied with the information China was giving them.
Read: The problem with China’s victory lap
If this is something short of complicity in a Chinese cover-up—which is what former National Security Adviser John Bolton has alleged of the WHO—it does point to a big vulnerability: The group’s membership includes transparent democracies and authoritarian states and systems in between, which means the information the WHO puts out is only as good as what it’s getting from the likes of Xi Jinping and Russian President Vladimir Putin. North Korea, for instance, has reported absolutely no coronavirus cases, and the WHO isn’t really in a position to say otherwise.
The structure also gives WHO leaders like Tedros an incentive not to anger member states, and this is as true of China as it is of countries with significantly less financial clout. During the Ebola epidemic in 2014, Clift said, WHO took months to declare a public-health emergency. “That’s three very small West African countries, and WHO didn’t want to upset them,” Clift said. “WHO didn’t cover itself in glory in that one.” The response this time has been much faster and better, in Clift’s observation. “It doesn’t mean it shouldn’t be examined afterwards to see what they could have done better,” he said. “And one should really investigate the origins of what happened in China.”
The WHO has also shown, however, that it can walk the line between the need for cooperation and information-sharing from member states and the need to hold them accountable for mistakes. During the SARS outbreak in 2003, a WHO spokesman criticized China for its lack of transparency and preparation, which had allowed the virus to spread unchecked. China even later admitted to mistakes in handling the outbreak.
No such critique has been forthcoming this time. One study found that China could have limited its own infections by up to 95 percent had the government acted in that early period when doctors were first raising the alarm and the Chinese Communist Party was still denying the extent of the problem. “The WHO at that time didn’t do their job,” Xiao said. “The opposite: They actually compounded Chinese authorities’ misinformation for a few weeks. That is, to me, unforgivable.”
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This transmission electron microscope image shows SARS-CoV-2, the virus that causes COVID-19, isolated from a patient in the U.S. Virus particles are shown emerging from the surface of cells cultured in the lab. The spikes on the outer edge of the virus particles give coronaviruses their name, crown-like. Credit: NIAID-RML
Yellow-winged Bat (Lavia frons) and youngster cling to a thorn in an acacia tree in Tarangire National Park of Tanzania.
Bats in Tanzania, including potentially the yellow-winged bat (Lavia frons), can carry various viruses like rabies-related lyssaviruses, paramyxoviruses (Ebola/Nipah-like), and coronaviruses, posing spillover risks to humans, though specific disease prevalence in this bat is less documented than general bat virus reservoirs; direct contact with any bat should be avoided as they are natural reservoirs for many pathogens.
3/5/2020 Mike Orazzi | Staff
The handshake free zone during the Summer Job Fair at New Britain City Hall on Thursday afternoon. #Coronaviruses #germs #COVID-19
Since the outbreak of coronavirus, there has been considerable discussion on the origin of the causative virus, SARS-CoV-2. A new study by The Scripps Research Institute based on genome sequence data from SARS-CoV-2 and related viruses hasn’t found any evidence that the virus was made in a laboratory or otherwise engineered.
For this study, scientists compared the available genome sequence data for known coronavirus strains. They firmly determined that SARS-CoV-2 originated through natural processes.
Coronaviruses are a large family of viruses that can cause illnesses ranging widely in severity. SARS-CoV-2 is the seventh coronavirus known to infect humans; SARS-CoV, MERS-CoV, and SARS-CoV-2 can cause severe disease, whereas HKU1, NL63, OC43, and 229E are associated with mild symptoms.
The first known severe illness caused by a coronavirus emerged with the 2003 Severe Acute Respiratory Syndrome (SARS) epidemic in China. A second severe disease outbreak began in 2012 in Saudi Arabia with the Middle East Respiratory Syndrome (MERS).
On December 31 of last year, Chinese authorities cautioned the World Health Organization of an outbreak of a novel strain of coronavirus causing severe illness, which was accordingly named SARS-CoV-2. As of February 20, 2020, about 167,500 COVID-19 cases have been documented, albeit a lot progressively mild cases have likely gone undiagnosed. The virus has killed more than 6,600 people.
Shortly after the outbreak, Chinese scientists sequenced the genome of SARS-CoV-2 and made the data available to scientists worldwide. The data suggests that Chinese authorities rapidly detected the epidemic and that the number of COVID-19 cases has been increasing because of human to the human transmission after a single introduction into the human population.
Scientists in this study used this sequencing data to explore the origins and evolution of SARS-CoV-2 by focusing in on several tell-tale features of the virus.
Scientists analyzed the genetic template for spike proteins, armatures on the outside of the virus that it uses to grab and penetrate the external wall of human and animal cells. More specifically, they focused on two essential features of the spike protein: the receptor-binding domain (RBD), a kind of grappling hook that grips onto host cells, and the cleavage site, a molecular can opener that allows the virus to crack open and enter host cells.
Scientists found that the RBD part of the SARS-CoV-2 spike proteins had evolved to viably target a molecular feature outwardly of human cells called ACE2, a receptor involved in regulating blood pressure. The SARS-CoV-2 spike protein was so powerful at binding the human cells.
This proof for natural evolution was upheld by data on SARS-CoV-2’s backbone—its overall molecular structure. On the off chance that somebody was trying to build a new coronavirus as a pathogen, they would have developed it from the foundation of the virus known to cause illness. In any case, the scientists found that the SARS-CoV-2 backbone varied significantly from those of definitely known coronaviruses and, for the most part, looked like related viruses found in bats and pangolins.
Kristian Andersen, Ph.D., an associate professor of immunology and microbiology at Scripps Research, said, “These two features of the virus, the mutations in the RBD portion of the spike protein and its distinct backbone, rule out laboratory manipulation as a potential origin for SARS-CoV-2.”
Josie Golding, Ph.D., epidemics lead at UK-based Wellcome Trust, said, “The findings are “crucially important to bring an evidence-based view to the rumors that have been circulating about the origins of the virus (SARS-CoV-2) causing COVID-19.”
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Journal Reference:
Correspondence
Published: 17 March 2020
The proximal origin of SARS-CoV-2
Kristian G. Andersen, Andrew Rambaut, W. Ian Lipkin, Edward C. Holmes & Robert F. Garry
Nature Medicine (2020)Cite this article
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To the Editor — Since the first reports of novel pneumonia (COVID-19) in Wuhan, Hubei province, China1,2, there has been considerable discussion on the origin of the causative virus, SARS-CoV-23 (also referred to as HCoV-19)4. Infections with SARS-CoV-2 are now widespread, and as of 11 March 2020, 121,564 cases have been confirmed in more than 110 countries, with 4,373 deaths5.
SARS-CoV-2 is the seventh coronavirus known to infect humans; SARS-CoV, MERS-CoV and SARS-CoV-2 can cause severe disease, whereas HKU1, NL63, OC43 and 229E are associated with mild symptoms6. Here we review what can be deduced about the origin of SARS-CoV-2 from comparative analysis of genomic data. We offer a perspective on the notable features of the SARS-CoV-2 genome and discuss scenarios by which they could have arisen. Our analyses clearly show that SARS-CoV-2 is not a laboratory construct or a purposefully manipulated virus.
Notable features of the SARS-CoV-2 genome
Our comparison of alpha- and betacoronaviruses identifies two notable genomic features of SARS-CoV-2: (i) on the basis of structural studies7,8,9 and biochemical experiments1,9,10, SARS-CoV-2 appears to be optimized for binding to the human receptor ACE2; and (ii) the spike protein of SARS-CoV-2 has a functional polybasic (furin) cleavage site at the S1–S2 boundary through the insertion of 12 nucleotides8, which additionally led to the predicted acquisition of three O-linked glycans around the site.
1. Mutations in the receptor-binding domain of SARS-CoV-2
The receptor-binding domain (RBD) in the spike protein is the most variable part of the coronavirus genome1,2. Six RBD amino acids have been shown to be critical for binding to ACE2 receptors and for determining the host range of SARS-CoV-like viruses7. With coordinates based on SARS-CoV, they are Y442, L472, N479, D480, T487 and Y4911, which correspond to L455, F486, Q493, S494, N501 and Y505 in SARS-CoV-27. Five of these six residues differ between SARS-CoV-2 and SARS-CoV (Fig. 1a). On the basis of structural studies7,8,9 and biochemical experiments1,9,10, SARS-CoV-2 seems to have an RBD that binds with high affinity to ACE2 from humans, ferrets, cats and other species with high receptor homology7.
Fig. 1: Features of the spike protein in human SARS-CoV-2 and related coronaviruses.
figure1
a, Mutations in contact residues of the SARS-CoV-2 spike protein. The spike protein of SARS-CoV-2 (red bar at top) was aligned against the most closely related SARS-CoV-like coronaviruses and SARS-CoV itself. Key residues in the spike protein that make contact to the ACE2 receptor are marked with blue boxes in both SARS-CoV-2 and related viruses, including SARS-CoV (Urbani strain). b, Acquisition of polybasic cleavage site and O-linked glycans. Both the polybasic cleavage site and the three adjacent predicted O-linked glycans are unique to SARS-CoV-2 and were not previously seen in lineage B betacoronaviruses. Sequences shown are from NCBI GenBank, accession codes MN908947, MN996532, AY278741, KY417146 and MK211376. The pangolin coronavirus sequences are a consensus generated from SRR10168377 and SRR10168378 (NCBI BioProject PRJNA573298)29,30.
Full size image
While the analyses above suggest that SARS-CoV-2 may bind human ACE2 with high affinity, computational analyses predict that the interaction is not ideal7 and that the RBD sequence is different from those shown in SARS-CoV to be optimal for receptor binding7,11. Thus, the high-affinity binding of the SARS-CoV-2 spike protein to human ACE2 is most likely the result of natural selection on a human or human-like ACE2 that permits another optimal binding solution to arise. This is strong evidence that SARS-CoV-2 is not the product of purposeful manipulation.
2. Polybasic furin cleavage site and O-linked glycans
The second notable feature of SARS-CoV-2 is a polybasic cleavage site (RRAR) at the junction of S1 and S2, the two subunits of the spike8 (Fig. 1b). This allows effective cleavage by furin and other proteases and has a role in determining viral infectivity and host range12. In addition, a leading proline is also inserted at this site in SARS-CoV-2; thus, the inserted sequence is PRRA (Fig. 1b). The turn created by the proline is predicted to result in the addition of O-linked glycans to S673, T678 and S686, which flank the cleavage site and are unique to SARS-CoV-2 (Fig. 1b). Polybasic cleavage sites have not been observed in related ‘lineage B’ betacoronaviruses, although other human betacoronaviruses, including HKU1 (lineage A), have those sites and predicted O-linked glycans13. Given the level of genetic variation in the spike, it is likely that SARS-CoV-2-like viruses with partial or full polybasic cleavage sites will be discovered in other species.
The functional consequence of the polybasic cleavage site in SARS-CoV-2 is unknown, and it will be important to determine its impact on transmissibility and pathogenesis in animal models. Experiments with SARS-CoV have shown that insertion of a furin cleavage site at the S1–S2 junction enhances cell–cell fusion without affecting viral entry14. In addition, efficient cleavage of the MERS-CoV spike enables MERS-like coronaviruses from bats to infect human cells15. In avian influenza viruses, rapid replication and transmission in highly dense chicken populations selects for the acquisition of polybasic cleavage sites in the hemagglutinin (HA) protein16, which serves a function similar to that of the coronavirus spike protein. Acquisition of polybasic cleavage sites in HA, by insertion or recombination, converts low-pathogenicity avian influenza viruses into highly pathogenic forms16. The acquisition of polybasic cleavage sites by HA has also been observed after repeated passage in cell culture or through animals17.
The function of the predicted O-linked glycans is unclear, but they could create a ‘mucin-like domain’ that shields epitopes or key residues on the SARS-CoV-2 spike protein18. Several viruses utilize mucin-like domains as glycan shields involved immunoevasion18. Although prediction of O-linked glycosylation is robust, experimental studies are needed to determine if these sites are used in SARS-CoV-2.
Theories of SARS-CoV-2 origins
It is improbable that SARS-CoV-2 emerged through laboratory manipulation of a related SARS-CoV-like coronavirus. As noted above, the RBD of SARS-CoV-2 is optimized for binding to human ACE2 with an efficient solution different from those previously predicted7,11. Furthermore, if genetic manipulation had been performed, one of the several reverse-genetic systems available for betacoronaviruses would probably have been used19. However, the genetic data irrefutably show that SARS-CoV-2 is not derived from any previously used virus backbone20. Instead, we propose two scenarios that can plausibly explain the origin of SARS-CoV-2: (i) natural selection in an animal host before zoonotic transfer; and (ii) natural selection in humans following zoonotic transfer. We also discuss whether selection during passage could have given rise to SARS-CoV-2.
1. Natural selection in an animal host before zoonotic transfer
As many early cases of COVID-19 were linked to the Huanan market in Wuhan1,2, it is possible that an animal source was present at this location. Given the similarity of SARS-CoV-2 to bat SARS-CoV-like coronaviruses2, it is likely that bats serve as reservoir hosts for its progenitor. Although RaTG13, sampled from a Rhinolophus affinis bat1, is ~96% identical overall to SARS-CoV-2, its spike diverges in the RBD, which suggests that it may not bind efficiently to human ACE27 (Fig. 1a).
Malayan pangolins (Manis javanica) illegally imported into Guangdong province contain coronaviruses similar to SARS-CoV-221. Although the RaTG13 bat virus remains the closest to SARS-CoV-2 across the genome1, some pangolin coronaviruses exhibit strong similarity to SARS-CoV-2 in the RBD, including all six key RBD residues21 (Fig. 1). This clearly shows that the SARS-CoV-2 spike protein optimized for binding to human-like ACE2 is the result of natural selection.
Neither the bat betacoronaviruses nor the pangolin betacoronaviruses sampled thus far have polybasic cleavage sites. Although no animal coronavirus has been identified that is sufficiently similar to have served as the direct progenitor of SARS-CoV-2, the diversity of coronaviruses in bats and other species is massively undersampled. Mutations, insertions and deletions can occur near the S1–S2 junction of coronaviruses22, which shows that the polybasic cleavage site can arise by a natural evolutionary process. For a precursor virus to acquire both the polybasic cleavage site and mutations in the spike protein suitable for binding to human ACE2, an animal host would probably have to have a high population density (to allow natural selection to proceed efficiently) and an ACE2-encoding gene that is similar to the human ortholog.
2. Natural selection in humans following zoonotic transfer
It is possible that a progenitor of SARS-CoV-2 jumped into humans, acquiring the genomic features described above through adaptation during undetected human-to-human transmission. Once acquired, these adaptations would enable the pandemic to take off and produce a sufficiently large cluster of cases to trigger the surveillance system that detected it1,2.
All SARS-CoV-2 genomes sequenced so far have the genomic features described above and are thus derived from a common ancestor that had them too. The presence in pangolins of an RBD very similar to that of SARS-CoV-2 means that we can infer this was also probably in the virus that jumped to humans. This leaves the insertion of polybasic cleavage site to occur during human-to-human transmission.
Estimates of the timing of the most recent common ancestor of SARS-CoV-2 made with current sequence data point to emergence of the virus in late November 2019 to early December 201923, compatible with the earliest retrospectively confirmed cases24. Hence, this scenario presumes a period of unrecognized transmission in humans between the initial zoonotic event and the acquisition of the polybasic cleavage site. Sufficient opportunity could have arisen if there had been many prior zoonotic events that produced short chains of human-to-human transmission over an extended period. This is essentially the situation for MERS-CoV, for which all human cases are the result of repeated jumps of the virus from dromedary camels, producing single infections or short transmission chains that eventually resolve, with no adaptation to sustained transmission25.
Studies of banked human samples could provide information on whether such cryptic spread has occurred. Retrospective serological studies could also be informative, and a few such studies have been conducted showing low-level exposures to SARS-CoV-like coronaviruses in certain areas of China26. Critically, however, these studies could not have distinguished whether exposures were due to prior infections with SARS-CoV, SARS-CoV-2 or other SARS-CoV-like coronaviruses. Further serological studies should be conducted to determine the extent of prior human exposure to SARS-CoV-2.
3. Selection during passage
Basic research involving passage of bat SARS-CoV-like coronaviruses in cell culture and/or animal models has been ongoing for many years in biosafety level 2 laboratories across the world27, and there are documented instances of laboratory escapes of SARS-CoV28. We must therefore examine the possibility of an inadvertent laboratory release of SARS-CoV-2.
In theory, it is possible that SARS-CoV-2 acquired RBD mutations (Fig. 1a) during adaptation to passage in cell culture, as has been observed in studies of SARS-CoV11. The finding of SARS-CoV-like coronaviruses from pangolins with nearly identical RBDs, however, provides a much stronger and more parsimonious explanation of how SARS-CoV-2 acquired these via recombination or mutation19.
The acquisition of both the polybasic cleavage site and predicted O-linked glycans also argues against culture-based scenarios. New polybasic cleavage sites have been observed only after prolonged passage of low-pathogenicity avian influenza virus in vitro or in vivo17. Furthermore, a hypothetical generation of SARS-CoV-2 by cell culture or animal passage would have required prior isolation of a progenitor virus with very high genetic similarity, which has not been described. Subsequent generation of a polybasic cleavage site would have then required repeated passage in cell culture or animals with ACE2 receptors similar to those of humans, but such work has also not previously been described. Finally, the generation of the predicted O-linked glycans is also unlikely to have occurred due to cell-culture passage, as such features suggest the involvement of an immune system18.
Conclusions
In the midst of the global COVID-19 public-health emergency, it is reasonable to wonder why the origins of the pandemic matter. Detailed understanding of how an animal virus jumped species boundaries to infect humans so productively will help in the prevention of future zoonotic events. For example, if SARS-CoV-2 pre-adapted in another animal species, then there is the risk of future re-emergence events. In contrast, if the adaptive process occurred in humans, then even if repeated zoonotic transfers occur, they are unlikely to take off without the same series of mutations. In addition, identifying the closest viral relatives of SARS-CoV-2 circulating in animals will greatly assist studies of viral function. Indeed, the availability of the RaTG13 bat sequence helped reveal key RBD mutations and the polybasic cleavage site.
The genomic features described here may explain in part the infectiousness and transmissibility of SARS-CoV-2 in humans. Although the evidence shows that SARS-CoV-2 is not a purposefully manipulated virus, it is currently impossible to prove or disprove the other theories of its origin described here. However, since we observed all notable SARS-CoV-2 features, including the optimized RBD and polybasic cleavage site, in related coronaviruses in nature, we do not believe that any type of laboratory-based scenario is plausible.
More scientific data could swing the balance of evidence to favor one hypothesis over another. Obtaining related viral sequences from animal sources would be the most definitive way of revealing viral origins. For example, a future observation of an intermediate or fully formed polybasic cleavage site in a SARS-CoV-2-like virus from animals would lend even further support to the natural-selection hypotheses. It would also be helpful to obtain more genetic and functional data about SARS-CoV-2, including animal studies. The identification of a potential intermediate host of SARS-CoV-2, as well as sequencing of the virus from very early cases, would similarly be highly informative. Irrespective of the exact mechanisms by which SARS-CoV-2 originated via natural selection, the ongoing surveillance of pneumonia in humans and other animals is clearly of utmost importance.
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Acknowledgements
We thank all those who have contributed sequences to the GISAID database (www.gisaid.org/) and analyses to Virological.org (virological.org/). We thank M. Farzan for discussions, and the Wellcome Trust for support. K.G.A. is a Pew Biomedical Scholar and is supported by NIH grant U19AI135995. A.R. is supported by the Wellcome Trust (Collaborators Award 206298/Z/17/Z―ARTIC network) and the European Research Council (grant agreement no. 725422―ReservoirDOCS). E.C.H. is supported by an ARC Australian Laureate Fellowship (FL170100022). R.F.G. is supported by NIH grants U19AI135995, U54 HG007480 and U19AI142790.
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Department of Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA, USA
Kristian G. Andersen
Scripps Research Translational Institute, La Jolla, CA, USA
Kristian G. Andersen
Institute of Evolutionary Biology, University of Edinburgh, Edinburgh, UK
Andrew Rambaut
Center for Infection and Immunity, Mailman School of Public Health of Columbia University, New York, NY, USA
W. Ian Lipkin
Marie Bashir Institute for Infectious Diseases and Biosecurity, School of Life and Environmental Sciences and School of Medical Sciences, The University of Sydney, Sydney, Australia
Edward C. Holmes
Tulane University, School of Medicine, Department of Microbiology and Immunology, New Orleans, LA, USA
Robert F. Garry
Zalgen Labs, Germantown, MD, USA
Robert F. Garry
Corresponding author
Correspondence to Kristian G. Andersen.
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R.F.G. is co-founder of Zalgen Labs, a biotechnology company that develops countermeasures to emerging viruses.
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Andersen, K.G., Rambaut, A., Lipkin, W.I. et al. The proximal origin of SARS-CoV-2. Nat Med (2020). doi.org/10.1038/s41591-020-0820-9
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Since the Wisconsin supreme court ended the coronavirus measures immediately and without a reopening plan in place, there has been a constant flow of customers along Sheboygan's South Pier. As of today, the number of coronaviruses has risen almost 19% since last week. Those of us who are more community conscious are still wearing masks in public places and practicing social distancing. Those who are active customers in places like Prohibition Bistro are not. It's strange to me that in this "enlightened" nation wearing a mask to protect yourself and others has become a political statement.
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Here is a video I made to explain how to wash ands rub your hands efficiently with a hand sanitizer, step by step visual tutorial. I filmed it at CHU UCL Namur Hospital in Belgium.
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Hand sanitizer is a liquid or gel generally used to decrease infectious agents on the hands. Formulations of the alcohol-based type are preferable to hand washing with soap and water in most situations in the healthcare setting. It is generally more effective at killing microorganisms and better tolerated than soap and water. Hand washing should still be carried out if contamination can be seen or following the use of the toilet. The general use of non-alcohol based versions has no recommendations. Outside the health care setting, evidence to support the use of hand sanitizer over hand washing is poor. They are available as liquids, gels, and foams.
Hand sanitizer that contains at least 60 % alcohol or contains a "persistent antiseptic" should be used. Alcohol rubs kill many different kinds of bacteria, including antibiotic resistant bacteria and TB bacteria. 90% alcohol rubs are highly flammable, but kill many kinds of viruses, including enveloped viruses such as the flu virus, the common cold virus, coronaviruses, and HIV, though is notably ineffective against the rabies virus.
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This transmission electron microscope image shows SARS-CoV-2, the virus that causes COVID-19, isolated from a patient in the U.S. Virus particles are shown emerging from the surface of cells cultured in the lab. The spikes on the outer edge of the virus particles give coronaviruses their name, crown-like. Credit: NIAID-RML
Keeping fingers crossed.
Corona virus killer: “Nirmatrelvir is an oral protease inhibitor that is active against MPRO, a viral protease that plays an essential role in viral replication by cleaving the 2 viral polyproteins.1 It has demonstrated antiviral activity against all coronaviruses that are known to infect humans.2 Nirmatrelvir is packaged with ritonavir (as Paxlovid), a strong cytochrome P450 (CYP) 3A4 inhibitor and pharmacokinetic boosting agent that has been used to boost HIV protease inhibitors. Coadministration of ritonavir is required to increase nirmatrelvir concentrations to the target therapeutic range. The Food and Drug Administration (FDA) issued an Emergency Use Authorization (EUA) for ritonavir-boosted nirmatrelvir on December 22, 2021, for the treatment of COVID-19.3”
World leader, scientist, medical scientist, virologist, pharmacist, Professor Fangruida (F.D Smith) on the world epidemic and the nemesis and prevention of new coronaviruses and mutant viruses (Jacques Lucy) 2021v1.5)
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The Nemesis and Killer of New Coronavirus and Mutated Viruses-Joint Development of Vaccines and Drugs (Fangruida) July 2021
*The particularity of new coronaviruses and mutant viruses*The broad spectrum, high efficiency, redundancy, and safety of the new coronavirus vaccine design and development , Redundancy and safety
*New coronavirus drug chemical structure modification*Computer-aided design and drug screening. *"Antiviral biological missile", "New Coronavirus Anti-epidemic Tablets", "Composite Antiviral Oral Liquid", "New Coronavirus Long-acting Oral Tablets", "New Coronavirus Inhibitors" (injection)
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(World leader, scientist, medical scientist, biologist, virologist, pharmacist, FD Smith) "The Nemesis and Killer of New Coronavirus and Mutated Viruses-The Joint Development of Vaccines and Drugs" is an important scientific research document. Now it has been revised and re-published by the original author several times. The compilation is published and published according to the original manuscript to meet the needs of readers and netizens all over the world. At the same time, it is also of great benefit to the vast number of medical clinical drug researchers and various experts and scholars. We hope that it will be corrected in the reprint.------Compiled by Jacques Lucy in Geneva, August 2021
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According to Worldometer's real-time statistics, as of about 6:30 on July 23, there were a total of 193,323,815 confirmed cases of new coronary pneumonia worldwide, and a total of 4,150,213 deaths. There were 570,902 new confirmed cases and 8,766 new deaths worldwide in a single day. Data shows that the United States, Brazil, the United Kingdom, India, and Indonesia are the five countries with the largest number of new confirmed cases, and Indonesia, Brazil, Russia, South Africa, and India are the five countries with the largest number of new deaths.
The new coronavirus and delta mutant strains have been particularly serious in the recent past. Many countries and places have revived, and the number of cases has not decreased, but has increased.
, It is worthy of vigilance. Although many countries have strengthened vaccine prevention and control and other prevention and control measures, there are still many shortcomings and deficiencies in virus suppression and prevention. The new coronavirus and various mutant strains have a certain degree of antagonism to traditional drugs and most vaccines. Although most vaccines have great anti-epidemic properties and have important and irreplaceable effects and protection for prevention and treatment, it is impossible to completely prevent the spread and infection of viruses. The spread of the new crown virus pneumonia has been delayed for nearly two years. There are hundreds of millions of people infected worldwide, millions of deaths, and the time is long, the spread is widespread, and billions of people around the world are among them. The harm of the virus is quite terrible. This is well known. of. More urgent
What is more serious is that the virus and mutant strains have not completely retreated, especially many people are still infected and infected after being injected with various vaccines. The effectiveness of the vaccine and the resistance of the mutant virus are worthy of medical scientists, virologists, pharmacologists Zoologists and others seriously think and analyze. The current epidemic situation in European and American countries, China, Brazil, India, the United States, Russia and other countries has greatly improved from last year. However, relevant figures show that the global epidemic situation has not completely improved, and some countries and regions are still very serious. In particular, after extensive use of various vaccines, cases still occur, and in some places they are still very serious, which deserves a high degree of vigilance. Prevention and control measures are very important. In addition, vaccines and various anti-epidemic drugs are the first and necessary choices, and other methods are irreplaceable. It is particularly important to develop and develop comprehensive drugs, antiviral drugs, immune drugs, and genetic drugs. Research experiments on new coronaviruses and mutant viruses require more rigorous and in-depth data analysis, pathological pathogenic tissues, cell genes, molecular chemistry, quantum chemistry, etc., as well as vaccine molecular chemistry, quantum physics, quantum biology, cytological histology, medicinal chemistry, and drugs And the vaccine’s symptomatic, effectiveness, safety, long-term effectiveness, etc., of course, including tens of thousands of clinical cases and deaths and other first-hand information and evidence. The task of RNA (ribonucleic acid) in the human body is to use the information of our genetic material DNA to produce protein. It accomplishes this task in the ribosome, the protein-producing area of the cell. The ribosome is the place where protein biosynthesis occurs.
Medicine takes advantage of this: In vaccination, artificially produced mRNA provides ribosomes with instructions for constructing pathogen antigens to fight against—for example, the spike protein of coronavirus.
Traditional live vaccines or inactivated vaccines contain antigens that cause the immune system to react. The mRNA vaccine is produced in the cell
(1) The specificity of new coronaviruses and mutant viruses, etc., virology and quantum chemistry of mutant viruses, quantum physics, quantum microbiology
(2) New crown vaccine design, molecular biology and chemical structure, etc.
(3) The generality and particularity of the development of new coronavirus drugs
(4) Various drug design for new coronavirus pneumonia, medicinal chemistry, pharmacology, etc., cells, proteins, DNA, enzyme chemistry, pharmaceutical quantum chemistry, pharmaceutical quantum physics, human biochemistry, human biophysics, etc.
(5) The evolution and mutation characteristics of the new coronavirus and various mutant viruses, the long-term nature, repeatability, drug resistance, and epidemic resistance of the virus, etc.
(6) New coronavirus pneumonia and the infectious transmission of various new coronaviruses and their particularities
(7) The invisible transmission of new coronavirus pneumonia and various mutant viruses in humans or animals, and the mutual symbiosis of cross infection of various bacteria and viruses are also one of the very serious causes of serious harm to new coronaviruses and mutant viruses. Virology, pathology, etiology, gene sequencing, gene mapping, and a large number of analytical studies have shown that there are many cases in China, the United States, India, Russia, Brazil, and other countries.
(8) For the symptomatic prevention and treatment of the new coronavirus, the combination of various vaccines and various antiviral drugs is critical.
(9) According to the current epidemic situation and research judgments, the epidemic situation may improve in the next period of time and 2021-2022, and we are optimistic about its success. However, completely worry-free, it is still too early to win easily. It is not just relying on vaccination. Wearing masks to close the city and other prevention and control measures and methods can sit back and relax, and you can win a big victory. Because all kinds of research and exploration still require a lot of time and various experimental studies. It is not a day's work. A simple taste is very dangerous and harmful. The power and migratory explosiveness of viruses sometimes far exceed human thinking and perception. In the future, next year, or in the future, whether viruses and various evolutionary mutation viruses will re-attack, we still need to study, analyze, prevent and control, rather than being complacent, thinking that the vaccine can win a big victory is inevitably naive and ridiculous. Vaccine protection is very important, but it must not be taken carelessly. The mutation of the new crown virus is very rampant, and the cross-infection of recessive and virulent bacteria makes epidemic prevention and anti-epidemic very complicated.
(10) New crown virus pneumonia and the virus's stubbornness, strength, migration, susceptibility, multi-infectiousness, and occult. The effectiveness of various vaccines and the particularity of virus mutations The long-term hidden dangers and repeated recurrences of the new coronavirus
(11) The formation mechanism and invisible transmission of invisible viruses, asymptomatic infections and asymptomatic infections, asymptomatic transmission routes, asymptomatic infections, pathological pathogens. The spread and infection of viruses and mutated viruses, the blind spots and blind spots of virus vaccines, viral quantum chemistry and
The chemical and physical corresponding reactions at the meeting points of highly effective vaccine drugs, etc. The variability of mutated viruses is very complicated, and vaccination cannot completely prevent the spread of infection.
(12) New crown virus pneumonia and various respiratory infectious diseases are susceptible to infections in animals and humans, and are frequently recurring. This is one of the frequently-occurring and difficult diseases of common infectious diseases. Even with various vaccines and various antiviral immune drugs, it is difficult to completely prevent the occurrence and spread of viral pneumonia. Therefore, epidemic prevention and anti-epidemic is a major issue facing human society, and no country should take it lightly. The various costs that humans pay on this issue are very expensive, such as Ebola virus, influenza A virus,
Hepatitis virus,
Marburg virus
Sars coronavirus, plague, anthracnose, cholera
and many more. The B.1.1.7 mutant virus that was first discovered in the UK was renamed Alpha mutant virus; the B.1.351 that was first discovered in South Africa was renamed Beta mutant virus; the P.1 that was first discovered in Brazil was renamed Gamma mutant virus; the mutation was first discovered in India There are two branches of the virus. B.1.617.2, which was listed as "mutated virus of concern", was renamed Delta mutant virus, and B.1.617.1 of "mutated virus to be observed" was renamed Kappa mutant virus.
However, experts in many countries believe that the current vaccination is still effective, at least it can prevent severe illness and reduce deaths.
Delta mutant strain
According to the degree of risk, the WHO divides the new crown variant strains into two categories: worrying variant strains (VOC, variant of concern) and noteworthy variant strains (VOI, variant of interest). The former has caused many cases and a wide range of cases worldwide, and data confirms its transmission ability, strong toxicity, high power, complex migration, and high insidious transmission of infection. Resistance to vaccines may lead to the effectiveness of vaccines and clinical treatments. Decrease; the latter has confirmed cases of community transmission worldwide, or has been found in multiple countries, but has not yet formed a large-scale infection. Need to be very vigilant. Various cases and deaths in many countries in the world are related to this. In some countries, the epidemic situation is repeated, and it is also caused by various reasons and viruses, of course, including new cases and so on.
At present, VOC is the mutant strain that has the greatest impact on the epidemic and the greatest threat to the world, including: Alpha, Beta, Gamma and Delta. , Will the change of the spur protein in the VOC affect the immune protection effect of the existing vaccine, or whether it will affect the sensitivity of the VOC to the existing vaccine? For this problem, it is necessary to directly test neutralizing antibodies, such as those that can prevent the protection of infection. Antibodies recognize specific protein sequences on viral particles, especially those spike protein sequences used in mRNA vaccines.
(13) Countries around the world, especially countries and regions with more severe epidemics, have a large number of clinical cases, severe cases, and deaths, especially including many young and middle-aged patients, including those who have been vaccinated. The epidemic is more complicated and serious. Injecting various vaccines, taking strict control measures such as closing the city and wearing masks are very important and the effect is very obvious. However, the new coronavirus and mutant viruses are so repeated, their pathological pathogen research will also be very complicated and difficult. After the large-scale use of the vaccine, many people are still infected. In addition to the lack of prevention and control measures, it is very important that the viability of the new coronavirus and various mutant viruses is very important. It can escape the inactivation of the vaccine. It is very resistant to stubbornness. Therefore, the recurrence of new coronavirus pneumonia is very dangerous. What is more noteworthy is that medical scientists, virologists, pharmacists, biologists, zoologists and clinicians should seriously consider the correspondence between virus specificity and vaccine drugs, and the coupling of commonality and specificity. Only in this way can we find targets. Track and kill viruses. Only in this sense can the new crown virus produce a nemesis, put an end to and eradicate the new crown virus pneumonia. Of course, this is not a temporary battle, but a certain amount of time and process to achieve the goal in the end.
(14) The development and evolution of the natural universe and earth species, as well as life species. With the continuous evolution of human cell genes, microbes and bacterial viruses are constantly mutated and inherited. The new world will inevitably produce a variety of new pathogens.
And viruses. For example, neurological genetic disease, digestive system disease, respiratory system disease, blood system disease, cardiopulmonary system disease, etc., new diseases will continue to emerge as humans develop and evolve. Human migration to space, space diseases, space psychological diseases, space cell diseases, space genetic diseases, etc. Therefore, for the new coronavirus and mutated viruses, we must have sufficient knowledge and response, and do not think that it will be completely wiped out.
, And is not a scientific attitude. Viruses and humans mutually reinforce each other, and viruses and animals and plants mutually reinforce each other. This is the iron law of the natural universe. Human beings can only adapt to natural history, but cannot deliberately modify natural history.
Active immune products made from specific bacteria, viruses, rickettsiae, spirochetes, mycoplasma and other microorganisms and parasites are collectively called vaccines. Vaccination of animals can make the animal body have specific immunity. The principle of vaccines is to artificially attenuate, inactivate, and genetically attenuate pathogenic microorganisms (such as bacteria, viruses, rickettsia, etc.) and their metabolites. Purification and preparation methods, made into immune preparations for the prevention of infectious diseases. In terms of ingredients, the vaccine retains the antigenic properties and other characteristics of the pathogen, which can stimulate the body's immune response and produce protective antibodies. But it has no pathogenicity and does not cause harm to the body. When the body is exposed to this pathogen again, the immune system will produce more antibodies according to the previous memory to prevent the pathogen from invading or to fight against the damage to the body. (1) Inactivated vaccines: select pathogenic microorganisms with strong immunogenicity, culture them, inactivate them by physical or chemical methods, and then purify and prepare them. The virus species used in inactivated vaccines are generally virulent strains, but the use of attenuated attenuated strains also has good immunogenicity, such as the inactivated polio vaccine produced by the Sabin attenuated strain. The inactivated vaccine has lost its infectivity to the body, but still maintains its immunogenicity, which can stimulate the body to produce corresponding immunity and resist the infection of wild strains. Inactivated vaccines have a good immune effect. They can generally be stored for more than one year at 2～8°C without the risk of reversion of virulence; however, the inactivated vaccines cannot grow and reproduce after entering the human body. They stimulate the human body for a short time and must be strong and long-lasting. In general, adjuvants are required for immunity, and multiple injections in large doses are required, and the local immune protection of natural infection is lacking. Including bacteria, viruses, rickettsiae and toxoid preparations.
(2) Live attenuated vaccine: It is a vaccine made by using artificial targeted mutation methods or by screening live microorganisms with highly weakened or basically non-toxic virulence from the natural world. After inoculation, the live attenuated vaccine has a certain ability to grow and reproduce in the body, which can cause the body to have a reaction similar to a recessive infection or a mild infection, and it is widely used.
(3) Subunit vaccine: Among the multiple specific antigenic determinants carried by macromolecular antigens, only a small number of antigenic sites play an important role in the protective immune response. Separate natural proteins through chemical decomposition or controlled proteolysis, and extract bacteria and virusesVaccines made from fragments with immunological activity are screened out of the special protein structure of, called subunit vaccines. Subunit vaccines have only a few major surface proteins, so they can eliminate antibodies induced by many unrelated antigens, thereby reducing the side effects of the vaccine and related diseases and other side effects caused by the vaccine. (4) Genetically engineered vaccine: It uses DNA recombination biotechnology to direct the natural or synthetic genetic material in the pathogen coat protein that can induce the body's immune response into bacteria, yeast or mammalian cells to make it fully expressed. A vaccine prepared after purification. The application of genetic engineering technology can produce subunit vaccines that do not contain infectious substances, stable attenuated vaccines with live viruses as carriers, and multivalent vaccines that can prevent multiple diseases. This is the second-generation vaccine following the first-generation traditional vaccine. It has the advantages of safety, effectiveness, long-term immune response, and easy realization of combined immunization. It has certain advantages and effects.
New coronavirus drug development, drug targets and chemical modification.
Ligand-based drug design (or indirect drug design planning) relies on the knowledge of other molecules that bind to the target biological target. These other molecules can be used to derive pharmacophore models and structural modalities, which define the minimum necessary structural features that the molecule must have in order to bind to the target. In other words, a model of a biological target can be established based on the knowledge of the binding target, and the model can be used to design new molecular entities and other parts that interact with the target. Among them, the quantitative structure-activity relationship (QSAR) is included, in which the correlation between the calculated properties of the molecule and its experimentally determined biological activity can be derived. These QSAR relationships can be used to predict the activity of new analogs. The structure-activity relationship is very complicated.
Based on structure
Structure-based drug design relies on knowledge of the three-dimensional structure of biological targets obtained by methods such as X-ray crystallography or NMR spectroscopy and quantum chemistry. If the experimental structure of the target is not available, it is possible to create a homology model of the target and other standard models that can be compared based on the experimental structure of the relevant protein. Using the structure of biological targets, interactive graphics and medical chemists’ intuitive design can be used to predict drug candidates with high affinity and selective binding to the target. Various automatic calculation programs can also be used to suggest new drug candidates.
The current structure-based drug design methods can be roughly divided into three categories. The 3D method is to search a large database of small molecule 3D structures to find new ligands for a given receptor, in order to use a rapid approximate docking procedure to find those suitable for the receptor binding pocket. This method is called virtual screening. The second category is the de novo design of new ligands. In this method, by gradually assembling small fragments, a ligand molecule is established within the constraints of the binding pocket. These fragments can be single atoms or molecular fragments. The main advantage of this method is that it can propose novel structures that are not found in any database. The third method is to optimize the known ligand acquisition by evaluating the proposed analogs in the binding cavity.
Bind site ID
Binding site recognition is a step in structure-based design. If the structure of the target or a sufficiently similar homologue is determined in the presence of the bound ligand, the ligand should be observable in that structure, in which case the location of the binding site is small. However, there may not be an allosteric binding site of interest. In addition, only apo protein structures may be available, and it is not easy to reliably identify unoccupied sites that have the potential to bind ligands with high affinity. In short, the recognition of binding sites usually depends on the recognition of pits. The protein on the protein surface can hold molecules the size of drugs, etc. These molecules also have appropriate "hot spots" that drive ligand binding, hydrophobic surfaces, hydrogen bonding sites, and so on.
Drug design is a creative process of finding new drugs based on the knowledge of biological targets. The most common type of drug is small organic molecules that activate or inhibit the function of biomolecules, thereby producing therapeutic benefits for patients. In the most important sense, drug design involves the design of molecules with complementary shapes and charges that bind to their interacting biomolecular targets, and therefore will bind to them. Drug design often but does not necessarily rely on computer modeling techniques. A more accurate term is ligand design. Although the design technology for predicting binding affinity is quite successful, there are many other characteristics, such as bioavailability, metabolic half-life, side effects, etc., which must be optimized first before the ligand can become safe and effective. drug. These other features are usually difficult to predict and realize through reasonable design techniques. However, due to the high turnover rate, especially in the clinical stage of drug development, in the early stage of the drug design process, more attention is paid to the selection of drug candidates. The physical and chemical properties of these drug candidates are expected to be reduced during the development process. Complications are therefore more likely to lead to the approval of the marketed drug. In addition, in early drug discovery, in vitro experiments with computational methods are increasingly used to select compounds with more favorable ADME (absorption, distribution, metabolism, and excretion) and toxicological characteristics. A more accurate term is ligand design. Although the design technique for predicting binding affinity is quite successful, there are many other characteristics, such as bioavailability, metabolic half-life, side effects, iatrogenic effects, etc., which must be optimized first, and then the ligand To become safe and effective.
For drug targets, two aspects should be considered when selecting drug targets:
1. The effectiveness of the target, that is, the target is indeed related to the disease, and the symptoms of the disease can be effectively improved by regulating the physiological activity of the target.
2. The side effects of the target. If the regulation of the physiological activity of the target inevitably produces serious side effects, it is inappropriate to select it as the target of drug action or lose its important biological activity. The reference frame of the target should be expanded in multiple dimensions to have a big choice.
3. Search for biomolecular clues related to diseases: use genomics, proteomics and biochip technology to obtain biomolecular information related to diseases, and perform bioinformatics analysis to obtain clue information.
4. Perform functional research on related biomolecules to determine the target of candidate drugs. Multiple targets or individual targets.
5. Candidate drug targets, design small molecule compounds, and conduct pharmacological research at the molecular, cellular and overall animal levels.
Covalent bonding type
The covalent bonding type is an irreversible form of bonding, similar to the organic synthesis reaction that occurs. Covalent bonding types mostly occur in the mechanism of action of chemotherapeutic drugs. For example, alkylating agent anti-tumor drugs produce covalent bonding bonds to guanine bases in DNA, resulting in cytotoxic activity.
. Verify the effectiveness of the target.
Based on the targets that interact with drugs, that is, receptors in a broad sense, such as enzymes, receptors, ion channels, membranes, antigens, viruses, nucleic acids, polysaccharides, proteins, enzymes, etc., find and design reasonable drug molecules. Targets of action and drug screening should focus on multiple points. Drug intermediates and chemical modification. Combining the development of new drugs with the chemical structure modification of traditional drugs makes it easier to find breakthroughs and develop new antiviral drugs. For example, careful selection, modification and modification of existing related drugs that can successfully treat and recover a large number of cases, elimination and screening of invalid drugs from severe death cases, etc., are targeted, rather than screening and capturing needles in a haystack, aimless, with half the effort. Vaccine design should also be multi-pronged and focused. The broad-spectrum, long-term, safety, efficiency and redundancy of the vaccine should all be considered. In this way, it will be more powerful to deal with the mutation and evolution of the virus. Of course, series of vaccines, series of drugs, second-generation vaccines, third-generation vaccines, second-generation drugs, third-generation drugs, etc. can also be developed. Vaccines focus on epidemic prevention, and medicines focus on medical treatment. The two are very different; however, the two complement each other and complement each other. Therefore, in response to large-scale epidemics of infectious diseases, vaccines and various drugs are the nemesis and killers of viral diseases. Of course, it also includes other methods and measures, so I won't repeat them here.
Mainly through the comprehensive and accurate understanding of the structure of the drug and the receptor at the molecular level and even the electronic level, structure-based drug design and the understanding of the structure, function, and drug action mode of the target and the mechanism of physiological activity Mechanism-based drug design.
Compared with the traditional extensive pharmacological screening and lead compound optimization, it has obvious advantages.
Viral RNA replicase, also known as RNA-dependent RNA polymerase (RdRp) is responsible for the replication and transcription of RNA virus genome, and plays a very important role in the process of virus self-replication in host cells, and It also has a major impact on the mutation of the virus, it will change and accelerate the replication and recombination. Because RdRp from different viruses has a highly conserved core structure, the virus replicase is an important antiviral drug target and there are other selection sites, rather than a single isolated target target such as the new coronavirus As with various mutant viruses, inhibitors developed for viral replicase are expected to become a broad-spectrum antiviral drug. The currently well-known anti-coronavirus drug remdesivir (remdesivir) is a drug for viral replicase.
New antiviral therapies are gradually emerging. In addition to traditional polymerase and protease inhibitors, nucleic acid drugs, cell entry inhibitors, nucleocapsid inhibitors, and drugs targeting host cells are also increasingly appearing in the research and development of major pharmaceutical companies. The treatment of mutated viruses is becoming increasingly urgent. The development of drugs for the new coronavirus pneumonia is very important. It is not only for the current global new coronavirus epidemic, but more importantly, it is of great significance to face the severe pneumonia-respiratory infectious disease that poses a huge threat to humans.
There are many vaccines and related drugs developed for the new coronavirus pneumonia, and countries are vying for a while, mainly including the following:
Identification test, appearance, difference in loading, moisture, pH value, osmolality, polysaccharide content, free polysaccharide content, potency test, sterility test, pyrogen test, bacterial endotoxin test, abnormal toxicity test.
Among them: such as sterility inspection, pyrogen inspection, bacterial endotoxin, and abnormal toxicity inspection are indicators closely related to safety.
Polysaccharide content, free polysaccharide content, and efficacy test are indicators closely related to vaccine effectiveness.
Usually, a vaccine will go through a long research and development process of at least 8 years or even more than 20 years from research and development to marketing. The outbreak of the new crown epidemic requires no delay, and the design and development of vaccines is speeding up. It is not surprising in this special period. Of course, it is understandable that vaccine design, development and testing can be accelerated, shortened the cycle, and reduced some procedures. However, science needs to be rigorous and rigorous to achieve great results. The safety and effectiveness of vaccines are of the utmost importance. There must not be a single error. Otherwise, it will be counterproductive and need to be continuously improved and perfected.
Pre-clinical research: The screening of strains and cells is the basic guarantee to ensure the safety, effectiveness, and continuous supply of vaccines. Taking virus vaccines as an example, the laboratory stage needs to carry out strain screening, necessary strain attenuation, strain adaptation to the cultured cell matrix and stability studies in the process of passaging, and explore the stability of process quality, establish animal models, etc. . Choose mice, guinea pigs, rabbits or monkeys for animal experiments according to each vaccine situation. Pre-clinical research generally takes 5-10 years or longer on the premise that the process is controllable, the quality is stable, and it is safe and effective. In order to be safe and effective, a certain redundant design is also needed, so that the safety and effectiveness of the vaccine can be importantly guaranteed.
These include the establishment of vaccine strain/cell seed bank, production process research, quality research, stability research, animal safety evaluation and effectiveness evaluation, and clinical trial programs, etc.
The ARS-CoV-2 genome contains at least 10 ORFs. ORF1ab is converted into a polyprotein and processed into 16 non-structural proteins (NSP). These NSPs have a variety of functional biological activities, physical and chemical reactions, such as genome replication, induction of host mRNA cleavage, membrane rearrangement, autophagosome production, NSP polyprotein cleavage, capping, tailing, methylation, RNA double-stranded Uncoiling, etc., and others, play an important role in the virus life cycle. In addition, SARS-CoV-2 contains 4 structural proteins, namely spike (S), nucleocapsid (N), envelope (E) and membrane (M), all of which are encoded by the 3'end of the viral genome. Among the four structural proteins, S protein is a large multifunctional transmembrane protein that plays an important role in the process of virus adsorption, fusion, and injection into host cells, and requires in-depth observation and research.
1S protein is composed of S1 and S2 subunits, and each subunit can be further divided into different functional domains. The S1 subunit has 2 domains: NTD and RBD, and RBD contains conservative RBM. The S2 subunit has 3 structural domains: FP, HR1 and HR2. The S1 subunit is arranged at the top of the S2 subunit to form an immunodominant S protein.
The virus uses the host transmembrane protease Serine 2 (TMPRSS2) and the endosomal cysteine protease CatB/L to enter the cell. TMPRSS2 is responsible for the cleavage of the S protein to expose the FP region of the S2 subunit, which is responsible for initiating endosome-mediated host cell entry into it. It shows that TMPRSS2 is a host factor necessary for virus entry. Therefore, the use of drugs that inhibit this protease can achieve the purpose of treatment.
mRNA-1273
The mRNA encoding the full length of SARS-CoV-2, and the pre-spike protein fusion is encapsulated into lipid nanoparticles to form mRNA-1273 vaccine. It can induce a high level of S protein specific antiviral response. It can also consist of inactivated antigens or subunit antigens. The vaccine was quickly approved by the FDA and has entered phase II clinical trials. The company has announced the antibody data of 8 subjects who received different immunization doses. The 25ug dose group achieved an effect similar to the antibody level during the recovery period. The 100ug dose group exceeded the antibody level during the recovery period. In the 25ug and 100ug dose groups, the vaccine was basically safe and tolerable, while the 250ug dose group had 3 levels of systemic symptoms.
Viral vector vaccines can provide long-term high-level expression of antigen proteins, induce CTLs, and ultimately eliminate viral infections.
1, Ad5-nCov
A vaccine of SARS-CoV-2 recombinant spike protein expressed by recombinant, replication-deficient type 5 adenovirus (Ad5) vector. Load the optimized full-length S protein gene together with the plasminogen activation signal peptide gene into the E1 and E3 deleted Ad5 vectors. The vaccine is constructed by the Admax system derived from Microbix Biosystem. In phase I clinical trials, RBD (S1 subunit receptor binding domain) and S protein neutralizing antibody increased by 4 times 14 days after immunization, reaching a peak on 28 days. CD4+T and CD8+T cells reached a peak 14 days after immunization. The existing Ad5 immune resistance partially limits the response of antibodies and T cells. This study will be further conducted in the 18-60 age group, receiving 1/3 of the study dose, and follow-up for 3-6 months after immunization.
DNA vaccine
The introduction of antigen-encoding DNA and adjuvants as vaccines is the most innovative vaccine method. The transfected cells stably express the transgenic protein, similar to live viruses. The antigen will be endocytosed by immature DC, and finally provide antigen to CD4 + T, CD8 + T cells (by MHC differentiation) To induce humoral and cellular immunity. Some specificities of the virus and the new coronavirus mutant are different from general vaccines and other vaccines. Therefore, it is worth noting the gene expression of the vaccine. Otherwise, the effectiveness and efficiency of the vaccine will be questioned.
Live attenuated vaccine
DelNS1-SARS-CoV2-RBD
Basic influenza vaccine, delete NS1 gene. Express SARS-CoV-2 RBD domain. Cultured in CEF and MDCK (canine kidney cells) cells. It is more immunogenic than wild-type influenza virus and can be administered by nasal spray.
The viral genome is susceptible to mutation, antigen transfer and drift can occur, and spread among the population. Mutations can vary depending on the environmental conditions and population density of the geographic area. After screening and comparing 7,500 samples of infected patients, scientists found 198 mutations, indicating the evolutionary mutation of the virus in the human host. These mutations may form different virus subtypes, which means that even after vaccine immunization, viral infections may occur. A certain amount of increment and strengthening is needed here.
Inactivated vaccines, adenovirus vector vaccines, recombinant protein vaccines, nucleic acid vaccines, attenuated influenza virus vector vaccines, etc. According to relevant information, there are dozens of new coronavirus vaccines in the world, and more varieties are being developed and upgraded. Including the United States, Britain, China, Russia, India and other countries, there are more R&D and production units.
AZ vaccine
Modena vaccine
Lianya Vaccine
High-end vaccine
Pfizer vaccine
Pfizer-BioNTech
A large study found that the vaccine developed by Pfizer and German biotechnology company BioNTech is 95% effective in preventing COVID-19.
The vaccine is divided into two doses, which are injected every three weeks.
This vaccine uses a molecule called mRNA as its basis. mRNA is a molecular cousin of DNA, which contains instructions to build specific proteins; in this case, the mRNA in the vaccine encodes the coronavirus spike protein, which is attached to the surface of the virus and used to infect human cells. Once the vaccine enters the human body, it will instruct the body's cells to make this protein, and the immune system will learn to recognize and attack it.
Moderna
The vaccine developed by the American biotechnology company Moderna and the National Institute of Allergy and Infectious Diseases (NIAID) is also based on mRNA and is estimated to be 94.5% effective in preventing COVID-19.
Like Pfizer's vaccine, this vaccine is divided into two doses, but injected every four weeks instead of three weeks. Another difference is that the Moderna vaccine can be stored at minus 20 degrees Celsius instead of deep freezing like Pfizer vaccine. At present, the importance of one of the widely used vaccines is self-evident.
Oxford-AstraZeneca
The vaccine developed by the University of Oxford and the pharmaceutical company AstraZeneca is approximately 70% effective in preventing COVID-19-that is, in clinical trials, adjusting the dose seems to improve this effect.
In the population who received two high-dose vaccines (28 days apart), the effectiveness of the vaccine was about 62%; according to early analysis, the effectiveness of the vaccine in those patients who received the half-dose first and then the full-dose Is 90%. However, in clinical trials, participants taking half doses of the drug are wrong, and some scientists question whether these early results are representative.
Sinopharm Group (Beijing Institute of Biological Products, China)
China National Pharmaceutical Group Sinopharm and Beijing Institute of Biological Products have developed a vaccine from inactivated coronavirus (SARS-CoV-2). The inactivated coronavirus is an improved version that cannot be replicated.
Estimates of the effectiveness of vaccines against COVID-19 vary.
Gamaleya Institute
The Gamaleya Institute of the Russian Ministry of Health has developed a coronavirus vaccine candidate called Sputnik V. This vaccine contains two common cold viruses, adenoviruses, which have been modified so that they will not replicate in the human body; the modified virus also contains a gene encoding the coronavirus spike protein.
New crown drugs
There are many small molecule antiviral drug candidates in the clinical research stage around the world. Including traditional drugs in the past and various drugs yet to be developed, antiviral drugs, immune drugs, Gene drugs, compound drugs, etc.
(A) Molnupiravir
Molnupiravir is a prodrug of the nucleoside analog N4-hydroxycytidine (NHC), jointly developed by Merck and Ridgeback Biotherapeutics.
The positive rate of infectious virus isolation and culture in nasopharyngeal swabs was 0% (0/47), while that of patients in the placebo group was 24% (6/25). However, data from the Phase II/III study indicate that the drug has no benefit in preventing death or shortening the length of stay in hospitalized patients.
Therefore, Merck has decided to fully advance the research of 800mg molnupiravir in the treatment of patients with mild to moderate COVID-19.
(B) AT-527
AT-527 is a small molecule inhibitor of viral RNA polymerase, jointly developed by Roche and Atea. Not only can it be used as an oral therapy to treat hospitalized COVID-19 patients, but it also has the potential as a preventive treatment after exposure.
Including 70 high-risk COVID-19 hospitalized patients data, of which 62 patients' data can be used for virological analysis and evaluation. The results of interim virological analysis show that AT-527 can quickly reduce viral load. On day 2, compared with placebo, patients treated with AT-527 had a greater decline in viral load than the baseline level, and the continuous difference in viral load decline was maintained until day 8.
In addition, compared with the control group, the potent antiviral activity of AT-527 was also observed in patients with a baseline median viral load higher than 5.26 log10. When testing by RT-qPCR to assess whether the virus is cleared,
The safety aspect is consistent with previous studies. AT-527 showed good safety and tolerability, and no new safety problems or risks were found. Of course, there is still a considerable distance between experiment and clinical application, and a large amount of experimental data can prove it.
(C) Prokrutamide
Prokalamide is an AR (androgen receptor) antagonist. Activated androgen receptor AR can induce the expression of transmembrane serine protease (TMPRSS2). TMPRSS2 has a shearing effect on the new coronavirus S protein and ACE2, which can promote the binding of viral spike protein (S protein) to ACE, thereby promoting The virus enters the host cell. Therefore, inhibiting the androgen receptor may inhibit the viral infection process, and AR antagonists are expected to become anti-coronavirus drugs.
Positive results were obtained in a randomized, double-blind, placebo-controlled phase III clinical trial. The data shows that Prokalutamide reduces the risk of death in severely ill patients with new coronary disease by 92%, reduces the risk of new ventilator use by 92%, and shortens the length of hospital stay by 9 days. This shows that procrulamide has a certain therapeutic effect for patients with severe new coronary disease, which can significantly reduce the mortality of patients, and at the same time greatly reduce the new mechanical ventilation and shorten the patient's hospital stay.
With the continuous development of COVID-19 on a global scale, in addition to vaccines and prevention and control measures, we need a multi-pronged plan to control this disease. Oral antiviral therapy undoubtedly provides a convenient treatment option.
In addition, there are other drugs under development and experimentation. In dealing with the plague virus, in addition to the strict control of protective measures, it is very important that various efficient and safe vaccines and various drugs (including medical instruments, etc.) are the ultimate nemesis and killer of the virus.
(A) "Antiviral biological missiles" are mainly drugs for new coronaviruses and mutant viruses, which act on respiratory and lung diseases. The drugs use redundant designs to inhibit new coronaviruses and variant viruses.
(B) "New Coronavirus Epidemic Prevention Tablets" mainly use natural purified elements and chemical structure modifications.
(C) "Composite antiviral oral liquid" antiviral intermediate, natural antiviral plant, plus other preparations
(D) "New Coronavirus Long-acting Oral Tablets" Chemical modification of antiviral drugs, multiple targets, etc.
(E) "New Coronavirus Inhibitors" (injections) are mainly made of chemical drug structure modification and other preparations.
The development of these drugs mainly includes: drug target screening, structure-activity relationship, chemical modification, natural purification, etc., which require a lot of work and experimentation.
Humans need to vigorously develop drugs to deal with various viruses. These drugs are very important for the prevention and treatment of viruses and respiratory infectious diseases, influenza, pneumonia, etc.
The history of human development The history of human evolution, like all living species, will always be accompanied by the survival and development of microorganisms. It is not surprising that viruses and infectious diseases are frequent and prone to occur. The key is to prevent and control them before they happen.
This strain was first discovered in India in October 2020 and was initially called a "double mutant" virus by the media. According to the announcement by the Ministry of Health of India at the end of March this year, the "India New Coronavirus Genomics Alliance" composed of 10 laboratories found in samples collected in Maharashtra that this new mutant strain carries E484Q and L452R mutations. , May lead to immune escape and increased infectivity. This mutant strain was named B.1.617 by the WHO and was named with the Greek letter δ (delta) on May 31.
Shahid Jamil, the dean of the Trivedi School of Biological Sciences at Ashoka University in India and a virologist, said in an interview with the Shillong Times of India that this mutant strain called "double mutation" is not accurate enough. B. 1.617 contains a total of 15 mutations, of which 6 occur on the spike protein, of which 3 are more critical: L452R and E484Q mutations occur on the spike protein and the human cell "Angiotensin Converting Enzyme 2 (ACE2)" receptor In the bound region, L452R improves the ability of the virus to invade cells, and E484Q helps to enhance the immune escape of the virus; the third mutation P681R can also make the virus enter the cell more effectively. (Encyclopedia website)
There are currently dozens of antiviral COVID-19 therapies under development. The large drugmakers Merck and Pfizer are the closest to the end, as expected, a pair of oral antiviral COVID-19 therapies are undergoing advanced human clinical trials.
Merck's drug candidate is called monupiravir. It was originally developed as an influenza antiviral drug several years ago. However, preclinical studies have shown that it has a good effect on SARS and MERS coronavirus.
Monupiravir is currently undergoing in-depth large-scale Phase 3 human trials. So far, the data is so promising that the US government recently pre-ordered 1.7 million courses of drugs at a cost of $1.2 billion. If everything goes according to plan, the company hopes that the drug will be authorized by the FDA for emergency use and be on the market before the end of 2021.
Pfizer's large COVID-19 antiviral drug candidate is more unique. Currently known as PF-07321332, this drug is the first oral antiviral drug to enter human clinical trials, specifically targeting SARS-CoV-2.
Variant of Concern WHO Label First Detected in World First Detected in Washington State
B.1.1.7 Alpha United Kingdom, September 2020 January 2021
B.1.351 Beta South Africa, December 2020 February 2021
P.1 Gamma Brazil, April 2020 March 2021
B.1.617.2 Delta India, October 2020 April 2021
Although this particular molecule was developed in 2020 after the emergence of the new coronavirus, a somewhat related drug called PF-00835231 has been in operation for several years, targeting the original SARS virus. However, the new drug candidate PF-07321332 is designed as a simple pill that can be taken under non-hospital conditions in the initial stages of SARS-CoV-2 infection.
"The protease inhibitor binds to a viral enzyme and prevents the virus from replicating in the cell," Pfizer said when explaining the mechanism of its new antiviral drug. "Protease inhibitors have been effective in the treatment of other viral pathogens, such as HIV and hepatitis C virus, whether used alone or in combination with other antiviral drugs. Currently marketed therapeutic drugs for viral proteases are generally not toxic Therefore, such molecules may provide well-tolerated treatments against COVID-19."
Various studies on other types of antiviral drugs are also gaining momentum. For example, the new coronavirus pneumonia "antiviral biological missile", "new coronavirus prevention tablets", "composite antiviral oral liquid", "new coronavirus long-acting oral tablets", "new coronavirus inhibitors" (injections), etc., are worthy of attention. Like all kinds of vaccines, they will play a major role in preventing and fighting epidemics.
In addition, Japanese pharmaceutical company Shionoyoshi Pharmaceutical is currently conducting a phase 1 trial of a protease inhibitor similar to SARS-CoV-2. This is called S-217622, which is another oral antiviral drug, and hopes to provide people with an easy-to-take pill in the early stages of COVID-19. At present, the research and development of vaccines and various new crown drugs is very active and urgent. Time does not wait. With the passage of time, various new crown drugs will appear on the stage one after another, bringing the gospel to the complete victory of mankind.
The COVID-19 pandemic is far from over. The Delta mutant strain has quickly become the most prominent SARS-CoV-2 strain in the world. Although our vaccine is still maintained, it is clear that we need more tools to combat this new type of coronavirus. Delta will certainly not be the last new SARS-CoV-2 variant we encountered. Therefore, it is necessary for all mankind to persevere and fight the epidemic together.
Overcome illness and meet new challenges. The new crown epidemic and various mutated viruses are very important global epidemic prevention and anti-epidemic top priorities, especially for the current period of time. Vaccine injections, research and development of new drugs, strict prevention and control, wear masks, reduce gatherings, strictly control large gatherings, prevent the spread of various viruses Masks, disinfection and sterilization, lockdown of the city, vaccinations, accounting and testing are very important, but this does not mean that humans can completely overcome the virus. In fact, many spreading and new latently transmitted infections are still unsuccessful. There are detections, such as invisible patients, asymptomatic patients, migratory latent patients, new-onset patients, etc. The struggle between humans and the virus is still very difficult and complicated, and long-term efforts and exploration are still needed, especially for medical research on the new coronavirus. The origin of the disease, the course of the disease, the virus invaded The deep-level path and the reasons for the evolution and mutation of the new coronavirus and the particularity of prevention and treatment, etc.). Therefore, human beings should be highly vigilant and must not be taken lightly. The fierce battle between humans and various viruses must not be slackened. Greater efforts are needed to successfully overcome this pandemic, fully restore the normal life of the whole society, restore the normal production and work order, restore the normal operation of society, economy and culture, and give up food due to choking. Or eager for success, will pay a high price.
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Compilation postscript
Once Fang Ruida's research literature on the new crown virus and mutant virus was published, it has been enthusiastically praised by readers and netizens in dozens of countries around the world, and has proposed some amendments and suggestions. Hope to publish a multilingual version of the book as an emergency To meet the needs of many readers around the world, in the face of the new crown epidemic and the prevention and treatment of various mutant viruses, including the general public, college and middle school students, medical workers, medical colleagues and so on. According to the English original manuscript, it will be re-compiled and published. Inconsistencies will be revised separately. Thank you very much.
Jacques Lucy, Geneva, Switzerland, August 2021
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Leader mondial, scientifique, scientifique médical, virologue, pharmacien et professeur Fangruida (F.D Smith) sur l'épidémie mondiale et l'ennemi juré et la prévention des nouveaux coronavirus et virus mutants (Jacques Lucy 2021v1.5)
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L'ennemi juré et le tueur du nouveau coronavirus et des virus mutés - Développement conjoint de vaccins et de médicaments (Fangruida) Juillet 2021
* La particularité des nouveaux coronavirus et des virus mutants * Le large spectre, la haute efficacité, la redondance et la sécurité de la conception et du développement du nouveau vaccin contre le coronavirus, Redondance et sécurité
Coronavirus disease 2019 (COVID-19) is a contagious disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The first case was identified in Wuhan, China, in December 2019. The disease has since spread worldwide, leading to an ongoing pandemic.
Symptoms of COVID-19 are variable, but often include fever, cough, fatigue, breathing difficulties, and loss of smell and taste. Symptoms begin one to fourteen days after exposure to the virus. Of those people who develop noticeable symptoms, most (81%) develop mild to moderate symptoms (up to mild pneumonia), while 14% develop severe symptoms (dyspnea, hypoxia, or more than 50% lung involvement on imaging), and 5% suffer critical symptoms (respiratory failure, shock, or multiorgan dysfunction). Older people are more likely to have severe symptoms. At least a third of the people who are infected with the virus remain asymptomatic and do not develop noticeable symptoms at any point in time, but they still can spread the disease.[ Around 20% of those people will remain asymptomatic throughout infection, and the rest will develop symptoms later on, becoming pre-symptomatic rather than asymptomatic and therefore having a higher risk of transmitting the virus to others. Some people continue to experience a range of effects—known as long COVID—for months after recovery, and damage to organs has been observed. Multi-year studies are underway to further investigate the long-term effects of the disease.
The virus that causes COVID-19 spreads mainly when an infected person is in close contact[a] with another person. Small droplets and aerosols containing the virus can spread from an infected person's nose and mouth as they breathe, cough, sneeze, sing, or speak. Other people are infected if the virus gets into their mouth, nose or eyes. The virus may also spread via contaminated surfaces, although this is not thought to be the main route of transmission. The exact route of transmission is rarely proven conclusively, but infection mainly happens when people are near each other for long enough. People who are infected can transmit the virus to another person up to two days before they themselves show symptoms, as can people who do not experience symptoms. People remain infectious for up to ten days after the onset of symptoms in moderate cases and up to 20 days in severe cases. Several testing methods have been developed to diagnose the disease. The standard diagnostic method is by detection of the virus' nucleic acid by real-time reverse transcription polymerase chain reaction (rRT-PCR), transcription-mediated amplification (TMA), or by reverse transcription loop-mediated isothermal amplification (RT-LAMP) from a nasopharyngeal swab.
Preventive measures include physical or social distancing, quarantining, ventilation of indoor spaces, covering coughs and sneezes, hand washing, and keeping unwashed hands away from the face. The use of face masks or coverings has been recommended in public settings to minimise the risk of transmissions. Several vaccines have been developed and several countries have initiated mass vaccination campaigns.
Although work is underway to develop drugs that inhibit the virus, the primary treatment is currently symptomatic. Management involves the treatment of symptoms, supportive care, isolation, and experimental measures.
SIGNS AND SYSTOMS
Symptoms of COVID-19 are variable, ranging from mild symptoms to severe illness. Common symptoms include headache, loss of smell and taste, nasal congestion and rhinorrhea, cough, muscle pain, sore throat, fever, diarrhea, and breathing difficulties. People with the same infection may have different symptoms, and their symptoms may change over time. Three common clusters of symptoms have been identified: one respiratory symptom cluster with cough, sputum, shortness of breath, and fever; a musculoskeletal symptom cluster with muscle and joint pain, headache, and fatigue; a cluster of digestive symptoms with abdominal pain, vomiting, and diarrhea. In people without prior ear, nose, and throat disorders, loss of taste combined with loss of smell is associated with COVID-19.
Most people (81%) develop mild to moderate symptoms (up to mild pneumonia), while 14% develop severe symptoms (dyspnea, hypoxia, or more than 50% lung involvement on imaging) and 5% of patients suffer critical symptoms (respiratory failure, shock, or multiorgan dysfunction). At least a third of the people who are infected with the virus do not develop noticeable symptoms at any point in time. These asymptomatic carriers tend not to get tested and can spread the disease. Other infected people will develop symptoms later, called "pre-symptomatic", or have very mild symptoms and can also spread the virus.
As is common with infections, there is a delay between the moment a person first becomes infected and the appearance of the first symptoms. The median delay for COVID-19 is four to five days. Most symptomatic people experience symptoms within two to seven days after exposure, and almost all will experience at least one symptom within 12 days.
Most people recover from the acute phase of the disease. However, some people continue to experience a range of effects for months after recovery—named long COVID—and damage to organs has been observed. Multi-year studies are underway to further investigate the long-term effects of the disease.
CAUSE
TRANSMISSION
Coronavirus disease 2019 (COVID-19) spreads from person to person mainly through the respiratory route after an infected person coughs, sneezes, sings, talks or breathes. A new infection occurs when virus-containing particles exhaled by an infected person, either respiratory droplets or aerosols, get into the mouth, nose, or eyes of other people who are in close contact with the infected person. During human-to-human transmission, an average 1000 infectious SARS-CoV-2 virions are thought to initiate a new infection.
The closer people interact, and the longer they interact, the more likely they are to transmit COVID-19. Closer distances can involve larger droplets (which fall to the ground) and aerosols, whereas longer distances only involve aerosols. Larger droplets can also turn into aerosols (known as droplet nuclei) through evaporation. The relative importance of the larger droplets and the aerosols is not clear as of November 2020; however, the virus is not known to spread between rooms over long distances such as through air ducts. Airborne transmission is able to particularly occur indoors, in high risk locations such as restaurants, choirs, gyms, nightclubs, offices, and religious venues, often when they are crowded or less ventilated. It also occurs in healthcare settings, often when aerosol-generating medical procedures are performed on COVID-19 patients.
Although it is considered possible there is no direct evidence of the virus being transmitted by skin to skin contact. A person could get COVID-19 indirectly by touching a contaminated surface or object before touching their own mouth, nose, or eyes, though this is not thought to be the main way the virus spreads. The virus is not known to spread through feces, urine, breast milk, food, wastewater, drinking water, or via animal disease vectors (although some animals can contract the virus from humans). It very rarely transmits from mother to baby during pregnancy.
Social distancing and the wearing of cloth face masks, surgical masks, respirators, or other face coverings are controls for droplet transmission. Transmission may be decreased indoors with well maintained heating and ventilation systems to maintain good air circulation and increase the use of outdoor air.
The number of people generally infected by one infected person varies. Coronavirus disease 2019 is more infectious than influenza, but less so than measles. It often spreads in clusters, where infections can be traced back to an index case or geographical location. There is a major role of "super-spreading events", where many people are infected by one person.
A person who is infected can transmit the virus to others up to two days before they themselves show symptoms, and even if symptoms never appear. People remain infectious in moderate cases for 7–12 days, and up to two weeks in severe cases. In October 2020, medical scientists reported evidence of reinfection in one person.
VIROLOGY
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a novel severe acute respiratory syndrome coronavirus. It was first isolated from three people with pneumonia connected to the cluster of acute respiratory illness cases in Wuhan. All structural features of the novel SARS-CoV-2 virus particle occur in related coronaviruses in nature.
Outside the human body, the virus is destroyed by household soap, which bursts its protective bubble.
SARS-CoV-2 is closely related to the original SARS-CoV. It is thought to have an animal (zoonotic) origin. Genetic analysis has revealed that the coronavirus genetically clusters with the genus Betacoronavirus, in subgenus Sarbecovirus (lineage B) together with two bat-derived strains. It is 96% identical at the whole genome level to other bat coronavirus samples (BatCov RaTG13). The structural proteins of SARS-CoV-2 include membrane glycoprotein (M), envelope protein (E), nucleocapsid protein (N), and the spike protein (S). The M protein of SARS-CoV-2 is about 98% similar to the M protein of bat SARS-CoV, maintains around 98% homology with pangolin SARS-CoV, and has 90% homology with the M protein of SARS-CoV; whereas, the similarity is only around 38% with the M protein of MERS-CoV. The structure of the M protein resembles the sugar transporter SemiSWEET.
The many thousands of SARS-CoV-2 variants are grouped into clades. Several different clade nomenclatures have been proposed. Nextstrain divides the variants into five clades (19A, 19B, 20A, 20B, and 20C), while GISAID divides them into seven (L, O, V, S, G, GH, and GR).
Several notable variants of SARS-CoV-2 emerged in late 2020. Cluster 5 emerged among minks and mink farmers in Denmark. After strict quarantines and a mink euthanasia campaign, it is believed to have been eradicated. The Variant of Concern 202012/01 (VOC 202012/01) is believed to have emerged in the United Kingdom in September. The 501Y.V2 Variant, which has the same N501Y mutation, arose independently in South Africa.
SARS-CoV-2 VARIANTS
Three known variants of SARS-CoV-2 are currently spreading among global populations as of January 2021 including the UK Variant (referred to as B.1.1.7) first found in London and Kent, a variant discovered in South Africa (referred to as 1.351), and a variant discovered in Brazil (referred to as P.1).
Using Whole Genome Sequencing, epidemiology and modelling suggest the new UK variant ‘VUI – 202012/01’ (the first Variant Under Investigation in December 2020) transmits more easily than other strains.
PATHOPHYSIOLOGY
COVID-19 can affect the upper respiratory tract (sinuses, nose, and throat) and the lower respiratory tract (windpipe and lungs). The lungs are the organs most affected by COVID-19 because the virus accesses host cells via the enzyme angiotensin-converting enzyme 2 (ACE2), which is most abundant in type II alveolar cells of the lungs. The virus uses a special surface glycoprotein called a "spike" (peplomer) to connect to ACE2 and enter the host cell. The density of ACE2 in each tissue correlates with the severity of the disease in that tissue and decreasing ACE2 activity might be protective, though another view is that increasing ACE2 using angiotensin II receptor blocker medications could be protective. As the alveolar disease progresses, respiratory failure might develop and death may follow.
Whether SARS-CoV-2 is able to invade the nervous system remains unknown. The virus is not detected in the CNS of the majority of COVID-19 people with neurological issues. However, SARS-CoV-2 has been detected at low levels in the brains of those who have died from COVID-19, but these results need to be confirmed. SARS-CoV-2 could cause respiratory failure through affecting the brain stem as other coronaviruses have been found to invade the CNS. While virus has been detected in cerebrospinal fluid of autopsies, the exact mechanism by which it invades the CNS remains unclear and may first involve invasion of peripheral nerves given the low levels of ACE2 in the brain. The virus may also enter the bloodstream from the lungs and cross the blood-brain barrier to gain access to the CNS, possibly within an infected white blood cell.
The virus also affects gastrointestinal organs as ACE2 is abundantly expressed in the glandular cells of gastric, duodenal and rectal epithelium as well as endothelial cells and enterocytes of the small intestine.
The virus can cause acute myocardial injury and chronic damage to the cardiovascular system. An acute cardiac injury was found in 12% of infected people admitted to the hospital in Wuhan, China, and is more frequent in severe disease. Rates of cardiovascular symptoms are high, owing to the systemic inflammatory response and immune system disorders during disease progression, but acute myocardial injuries may also be related to ACE2 receptors in the heart. ACE2 receptors are highly expressed in the heart and are involved in heart function. A high incidence of thrombosis and venous thromboembolism have been found people transferred to Intensive care unit (ICU) with COVID-19 infections, and may be related to poor prognosis. Blood vessel dysfunction and clot formation (as suggested by high D-dimer levels caused by blood clots) are thought to play a significant role in mortality, incidences of clots leading to pulmonary embolisms, and ischaemic events within the brain have been noted as complications leading to death in people infected with SARS-CoV-2. Infection appears to set off a chain of vasoconstrictive responses within the body, constriction of blood vessels within the pulmonary circulation has also been posited as a mechanism in which oxygenation decreases alongside the presentation of viral pneumonia. Furthermore, microvascular blood vessel damage has been reported in a small number of tissue samples of the brains – without detected SARS-CoV-2 – and the olfactory bulbs from those who have died from COVID-19.
Another common cause of death is complications related to the kidneys. Early reports show that up to 30% of hospitalized patients both in China and in New York have experienced some injury to their kidneys, including some persons with no previous kidney problems.
Autopsies of people who died of COVID-19 have found diffuse alveolar damage, and lymphocyte-containing inflammatory infiltrates within the lung.
IMMUNOPATHOLOGY
Although SARS-CoV-2 has a tropism for ACE2-expressing epithelial cells of the respiratory tract, people with severe COVID-19 have symptoms of systemic hyperinflammation. Clinical laboratory findings of elevated IL-2, IL-7, IL-6, granulocyte-macrophage colony-stimulating factor (GM-CSF), interferon-γ inducible protein 10 (IP-10), monocyte chemoattractant protein 1 (MCP-1), macrophage inflammatory protein 1-α (MIP-1α), and tumour necrosis factor-α (TNF-α) indicative of cytokine release syndrome (CRS) suggest an underlying immunopathology.
Additionally, people with COVID-19 and acute respiratory distress syndrome (ARDS) have classical serum biomarkers of CRS, including elevated C-reactive protein (CRP), lactate dehydrogenase (LDH), D-dimer, and ferritin.
Systemic inflammation results in vasodilation, allowing inflammatory lymphocytic and monocytic infiltration of the lung and the heart. In particular, pathogenic GM-CSF-secreting T-cells were shown to correlate with the recruitment of inflammatory IL-6-secreting monocytes and severe lung pathology in people with COVID-19 . Lymphocytic infiltrates have also been reported at autopsy.
VIRAL AND HOST FACTORS
VIRUS PROTEINS
Multiple viral and host factors affect the pathogenesis of the virus. The S-protein, otherwise known as the spike protein, is the viral component that attaches to the host receptor via the ACE2 receptors. It includes two subunits: S1 and S2. S1 determines the virus host range and cellular tropism via the receptor binding domain. S2 mediates the membrane fusion of the virus to its potential cell host via the H1 and HR2, which are heptad repeat regions. Studies have shown that S1 domain induced IgG and IgA antibody levels at a much higher capacity. It is the focus spike proteins expression that are involved in many effective COVID-19 vaccines.
The M protein is the viral protein responsible for the transmembrane transport of nutrients. It is the cause of the bud release and the formation of the viral envelope. The N and E protein are accessory proteins that interfere with the host's immune response.
HOST FACTORS
Human angiotensin converting enzyme 2 (hACE2) is the host factor that SARS-COV2 virus targets causing COVID-19. Theoretically the usage of angiotensin receptor blockers (ARB) and ACE inhibitors upregulating ACE2 expression might increase morbidity with COVID-19, though animal data suggest some potential protective effect of ARB. However no clinical studies have proven susceptibility or outcomes. Until further data is available, guidelines and recommendations for hypertensive patients remain.
The virus' effect on ACE2 cell surfaces leads to leukocytic infiltration, increased blood vessel permeability, alveolar wall permeability, as well as decreased secretion of lung surfactants. These effects cause the majority of the respiratory symptoms. However, the aggravation of local inflammation causes a cytokine storm eventually leading to a systemic inflammatory response syndrome.
HOST CYTOKINE RESPONSE
The severity of the inflammation can be attributed to the severity of what is known as the cytokine storm. Levels of interleukin 1B, interferon-gamma, interferon-inducible protein 10, and monocyte chemoattractant protein 1 were all associated with COVID-19 disease severity. Treatment has been proposed to combat the cytokine storm as it remains to be one of the leading causes of morbidity and mortality in COVID-19 disease.
A cytokine storm is due to an acute hyperinflammatory response that is responsible for clinical illness in an array of diseases but in COVID-19, it is related to worse prognosis and increased fatality. The storm causes the acute respiratory distress syndrome, blood clotting events such as strokes, myocardial infarction, encephalitis, acute kidney injury, and vasculitis. The production of IL-1, IL-2, IL-6, TNF-alpha, and interferon-gamma, all crucial components of normal immune responses, inadvertently become the causes of a cytokine storm. The cells of the central nervous system, the microglia, neurons, and astrocytes, are also be involved in the release of pro-inflammatory cytokines affecting the nervous system, and effects of cytokine storms toward the CNS are not uncommon.
DIAGNOSIS
COVID-19 can provisionally be diagnosed on the basis of symptoms and confirmed using reverse transcription polymerase chain reaction (RT-PCR) or other nucleic acid testing of infected secretions. Along with laboratory testing, chest CT scans may be helpful to diagnose COVID-19 in individuals with a high clinical suspicion of infection. Detection of a past infection is possible with serological tests, which detect antibodies produced by the body in response to the infection.
VIRAL TESTING
The standard methods of testing for presence of SARS-CoV-2 are nucleic acid tests, which detects the presence of viral RNA fragments. As these tests detect RNA but not infectious virus, its "ability to determine duration of infectivity of patients is limited." The test is typically done on respiratory samples obtained by a nasopharyngeal swab; however, a nasal swab or sputum sample may also be used. Results are generally available within hours. The WHO has published several testing protocols for the disease.
A number of laboratories and companies have developed serological tests, which detect antibodies produced by the body in response to infection. Several have been evaluated by Public Health England and approved for use in the UK.
The University of Oxford's CEBM has pointed to mounting evidence that "a good proportion of 'new' mild cases and people re-testing positives after quarantine or discharge from hospital are not infectious, but are simply clearing harmless virus particles which their immune system has efficiently dealt with" and have called for "an international effort to standardize and periodically calibrate testing" On 7 September, the UK government issued "guidance for procedures to be implemented in laboratories to provide assurance of positive SARS-CoV-2 RNA results during periods of low prevalence, when there is a reduction in the predictive value of positive test results."
IMAGING
Chest CT scans may be helpful to diagnose COVID-19 in individuals with a high clinical suspicion of infection but are not recommended for routine screening. Bilateral multilobar ground-glass opacities with a peripheral, asymmetric, and posterior distribution are common in early infection. Subpleural dominance, crazy paving (lobular septal thickening with variable alveolar filling), and consolidation may appear as the disease progresses. Characteristic imaging features on chest radiographs and computed tomography (CT) of people who are symptomatic include asymmetric peripheral ground-glass opacities without pleural effusions.
Many groups have created COVID-19 datasets that include imagery such as the Italian Radiological Society which has compiled an international online database of imaging findings for confirmed cases. Due to overlap with other infections such as adenovirus, imaging without confirmation by rRT-PCR is of limited specificity in identifying COVID-19. A large study in China compared chest CT results to PCR and demonstrated that though imaging is less specific for the infection, it is faster and more sensitive.
Coding
In late 2019, the WHO assigned emergency ICD-10 disease codes U07.1 for deaths from lab-confirmed SARS-CoV-2 infection and U07.2 for deaths from clinically or epidemiologically diagnosed COVID-19 without lab-confirmed SARS-CoV-2 infection.
PATHOLOGY
The main pathological findings at autopsy are:
Macroscopy: pericarditis, lung consolidation and pulmonary oedema
Lung findings:
minor serous exudation, minor fibrin exudation
pulmonary oedema, pneumocyte hyperplasia, large atypical pneumocytes, interstitial inflammation with lymphocytic infiltration and multinucleated giant cell formation
diffuse alveolar damage (DAD) with diffuse alveolar exudates. DAD is the cause of acute respiratory distress syndrome (ARDS) and severe hypoxemia.
organisation of exudates in alveolar cavities and pulmonary interstitial fibrosis
plasmocytosis in BAL
Blood: disseminated intravascular coagulation (DIC); leukoerythroblastic reaction
Liver: microvesicular steatosis
PREVENTION
Preventive measures to reduce the chances of infection include staying at home, wearing a mask in public, avoiding crowded places, keeping distance from others, ventilating indoor spaces, washing hands with soap and water often and for at least 20 seconds, practising good respiratory hygiene, and avoiding touching the eyes, nose, or mouth with unwashed hands.
Those diagnosed with COVID-19 or who believe they may be infected are advised by the CDC to stay home except to get medical care, call ahead before visiting a healthcare provider, wear a face mask before entering the healthcare provider's office and when in any room or vehicle with another person, cover coughs and sneezes with a tissue, regularly wash hands with soap and water and avoid sharing personal household items.
The first COVID-19 vaccine was granted regulatory approval on 2 December by the UK medicines regulator MHRA. It was evaluated for emergency use authorization (EUA) status by the US FDA, and in several other countries. Initially, the US National Institutes of Health guidelines do not recommend any medication for prevention of COVID-19, before or after exposure to the SARS-CoV-2 virus, outside the setting of a clinical trial. Without a vaccine, other prophylactic measures, or effective treatments, a key part of managing COVID-19 is trying to decrease and delay the epidemic peak, known as "flattening the curve". This is done by slowing the infection rate to decrease the risk of health services being overwhelmed, allowing for better treatment of current cases, and delaying additional cases until effective treatments or a vaccine become available.
VACCINE
A COVID‑19 vaccine is a vaccine intended to provide acquired immunity against severe acute respiratory syndrome coronavirus 2 (SARS‑CoV‑2), the virus causing coronavirus disease 2019 (COVID‑19). Prior to the COVID‑19 pandemic, there was an established body of knowledge about the structure and function of coronaviruses causing diseases like severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS), which enabled accelerated development of various vaccine technologies during early 2020. On 10 January 2020, the SARS-CoV-2 genetic sequence data was shared through GISAID, and by 19 March, the global pharmaceutical industry announced a major commitment to address COVID-19.
In Phase III trials, several COVID‑19 vaccines have demonstrated efficacy as high as 95% in preventing symptomatic COVID‑19 infections. As of March 2021, 12 vaccines were authorized by at least one national regulatory authority for public use: two RNA vaccines (the Pfizer–BioNTech vaccine and the Moderna vaccine), four conventional inactivated vaccines (BBIBP-CorV, CoronaVac, Covaxin, and CoviVac), four viral vector vaccines (Sputnik V, the Oxford–AstraZeneca vaccine, Convidicea, and the Johnson & Johnson vaccine), and two protein subunit vaccines (EpiVacCorona and RBD-Dimer). In total, as of March 2021, 308 vaccine candidates were in various stages of development, with 73 in clinical research, including 24 in Phase I trials, 33 in Phase I–II trials, and 16 in Phase III development.
Many countries have implemented phased distribution plans that prioritize those at highest risk of complications, such as the elderly, and those at high risk of exposure and transmission, such as healthcare workers. As of 17 March 2021, 400.22 million doses of COVID‑19 vaccine have been administered worldwide based on official reports from national health agencies. AstraZeneca-Oxford anticipates producing 3 billion doses in 2021, Pfizer-BioNTech 1.3 billion doses, and Sputnik V, Sinopharm, Sinovac, and Johnson & Johnson 1 billion doses each. Moderna targets producing 600 million doses and Convidicea 500 million doses in 2021. By December 2020, more than 10 billion vaccine doses had been preordered by countries, with about half of the doses purchased by high-income countries comprising 14% of the world's population.
SOCIAL DISTANCING
Social distancing (also known as physical distancing) includes infection control actions intended to slow the spread of the disease by minimising close contact between individuals. Methods include quarantines; travel restrictions; and the closing of schools, workplaces, stadiums, theatres, or shopping centres. Individuals may apply social distancing methods by staying at home, limiting travel, avoiding crowded areas, using no-contact greetings, and physically distancing themselves from others. Many governments are now mandating or recommending social distancing in regions affected by the outbreak.
Outbreaks have occurred in prisons due to crowding and an inability to enforce adequate social distancing. In the United States, the prisoner population is aging and many of them are at high risk for poor outcomes from COVID-19 due to high rates of coexisting heart and lung disease, and poor access to high-quality healthcare.
SELF-ISOLATION
Self-isolation at home has been recommended for those diagnosed with COVID-19 and those who suspect they have been infected. Health agencies have issued detailed instructions for proper self-isolation. Many governments have mandated or recommended self-quarantine for entire populations. The strongest self-quarantine instructions have been issued to those in high-risk groups. Those who may have been exposed to someone with COVID-19 and those who have recently travelled to a country or region with the widespread transmission have been advised to self-quarantine for 14 days from the time of last possible exposure.
Face masks and respiratory hygiene
The WHO and the US CDC recommend individuals wear non-medical face coverings in public settings where there is an increased risk of transmission and where social distancing measures are difficult to maintain. This recommendation is meant to reduce the spread of the disease by asymptomatic and pre-symptomatic individuals and is complementary to established preventive measures such as social distancing. Face coverings limit the volume and travel distance of expiratory droplets dispersed when talking, breathing, and coughing. A face covering without vents or holes will also filter out particles containing the virus from inhaled and exhaled air, reducing the chances of infection. But, if the mask include an exhalation valve, a wearer that is infected (maybe without having noticed that, and asymptomatic) would transmit the virus outwards through it, despite any certification they can have. So the masks with exhalation valve are not for the infected wearers, and are not reliable to stop the pandemic in a large scale. Many countries and local jurisdictions encourage or mandate the use of face masks or cloth face coverings by members of the public to limit the spread of the virus.
Masks are also strongly recommended for those who may have been infected and those taking care of someone who may have the disease. When not wearing a mask, the CDC recommends covering the mouth and nose with a tissue when coughing or sneezing and recommends using the inside of the elbow if no tissue is available. Proper hand hygiene after any cough or sneeze is encouraged. Healthcare professionals interacting directly with people who have COVID-19 are advised to use respirators at least as protective as NIOSH-certified N95 or equivalent, in addition to other personal protective equipment.
HAND-WASHING AND HYGIENE
Thorough hand hygiene after any cough or sneeze is required. The WHO also recommends that individuals wash hands often with soap and water for at least 20 seconds, especially after going to the toilet or when hands are visibly dirty, before eating and after blowing one's nose. The CDC recommends using an alcohol-based hand sanitiser with at least 60% alcohol, but only when soap and water are not readily available. For areas where commercial hand sanitisers are not readily available, the WHO provides two formulations for local production. In these formulations, the antimicrobial activity arises from ethanol or isopropanol. Hydrogen peroxide is used to help eliminate bacterial spores in the alcohol; it is "not an active substance for hand antisepsis". Glycerol is added as a humectant.
SURFACE CLEANING
After being expelled from the body, coronaviruses can survive on surfaces for hours to days. If a person touches the dirty surface, they may deposit the virus at the eyes, nose, or mouth where it can enter the body cause infection. Current evidence indicates that contact with infected surfaces is not the main driver of Covid-19, leading to recommendations for optimised disinfection procedures to avoid issues such as the increase of antimicrobial resistance through the use of inappropriate cleaning products and processes. Deep cleaning and other surface sanitation has been criticized as hygiene theater, giving a false sense of security against something primarily spread through the air.
The amount of time that the virus can survive depends significantly on the type of surface, the temperature, and the humidity. Coronaviruses die very quickly when exposed to the UV light in sunlight. Like other enveloped viruses, SARS-CoV-2 survives longest when the temperature is at room temperature or lower, and when the relative humidity is low (<50%).
On many surfaces, including as glass, some types of plastic, stainless steel, and skin, the virus can remain infective for several days indoors at room temperature, or even about a week under ideal conditions. On some surfaces, including cotton fabric and copper, the virus usually dies after a few hours. As a general rule of thumb, the virus dies faster on porous surfaces than on non-porous surfaces.
However, this rule is not absolute, and of the many surfaces tested, two with the longest survival times are N95 respirator masks and surgical masks, both of which are considered porous surfaces.
Surfaces may be decontaminated with 62–71 percent ethanol, 50–100 percent isopropanol, 0.1 percent sodium hypochlorite, 0.5 percent hydrogen peroxide, and 0.2–7.5 percent povidone-iodine. Other solutions, such as benzalkonium chloride and chlorhexidine gluconate, are less effective. Ultraviolet germicidal irradiation may also be used. The CDC recommends that if a COVID-19 case is suspected or confirmed at a facility such as an office or day care, all areas such as offices, bathrooms, common areas, shared electronic equipment like tablets, touch screens, keyboards, remote controls, and ATM machines used by the ill persons should be disinfected. A datasheet comprising the authorised substances to disinfection in the food industry (including suspension or surface tested, kind of surface, use dilution, disinfectant and inocuylum volumes) can be seen in the supplementary material of.
VENTILATION AND AIR FILTRATION
The WHO recommends ventilation and air filtration in public spaces to help clear out infectious aerosols.
HEALTHY DIET AND LIFESTYLE
The Harvard T.H. Chan School of Public Health recommends a healthy diet, being physically active, managing psychological stress, and getting enough sleep.
While there is no evidence that vitamin D is an effective treatment for COVID-19, there is limited evidence that vitamin D deficiency increases the risk of severe COVID-19 symptoms. This has led to recommendations for individuals with vitamin D deficiency to take vitamin D supplements as a way of mitigating the risk of COVID-19 and other health issues associated with a possible increase in deficiency due to social distancing.
TREATMENT
There is no specific, effective treatment or cure for coronavirus disease 2019 (COVID-19), the disease caused by the SARS-CoV-2 virus. Thus, the cornerstone of management of COVID-19 is supportive care, which includes treatment to relieve symptoms, fluid therapy, oxygen support and prone positioning as needed, and medications or devices to support other affected vital organs.
Most cases of COVID-19 are mild. In these, supportive care includes medication such as paracetamol or NSAIDs to relieve symptoms (fever, body aches, cough), proper intake of fluids, rest, and nasal breathing. Good personal hygiene and a healthy diet are also recommended. The U.S. Centers for Disease Control and Prevention (CDC) recommend that those who suspect they are carrying the virus isolate themselves at home and wear a face mask.
People with more severe cases may need treatment in hospital. In those with low oxygen levels, use of the glucocorticoid dexamethasone is strongly recommended, as it can reduce the risk of death. Noninvasive ventilation and, ultimately, admission to an intensive care unit for mechanical ventilation may be required to support breathing. Extracorporeal membrane oxygenation (ECMO) has been used to address the issue of respiratory failure, but its benefits are still under consideration.
Several experimental treatments are being actively studied in clinical trials. Others were thought to be promising early in the pandemic, such as hydroxychloroquine and lopinavir/ritonavir, but later research found them to be ineffective or even harmful. Despite ongoing research, there is still not enough high-quality evidence to recommend so-called early treatment. Nevertheless, in the United States, two monoclonal antibody-based therapies are available for early use in cases thought to be at high risk of progression to severe disease. The antiviral remdesivir is available in the U.S., Canada, Australia, and several other countries, with varying restrictions; however, it is not recommended for people needing mechanical ventilation, and is discouraged altogether by the World Health Organization (WHO), due to limited evidence of its efficacy.
PROGNOSIS
The severity of COVID-19 varies. The disease may take a mild course with few or no symptoms, resembling other common upper respiratory diseases such as the common cold. In 3–4% of cases (7.4% for those over age 65) symptoms are severe enough to cause hospitalization. Mild cases typically recover within two weeks, while those with severe or critical diseases may take three to six weeks to recover. Among those who have died, the time from symptom onset to death has ranged from two to eight weeks. The Italian Istituto Superiore di Sanità reported that the median time between the onset of symptoms and death was twelve days, with seven being hospitalised. However, people transferred to an ICU had a median time of ten days between hospitalisation and death. Prolonged prothrombin time and elevated C-reactive protein levels on admission to the hospital are associated with severe course of COVID-19 and with a transfer to ICU.
Some early studies suggest 10% to 20% of people with COVID-19 will experience symptoms lasting longer than a month.[191][192] A majority of those who were admitted to hospital with severe disease report long-term problems including fatigue and shortness of breath. On 30 October 2020 WHO chief Tedros Adhanom warned that "to a significant number of people, the COVID virus poses a range of serious long-term effects". He has described the vast spectrum of COVID-19 symptoms that fluctuate over time as "really concerning." They range from fatigue, a cough and shortness of breath, to inflammation and injury of major organs – including the lungs and heart, and also neurological and psychologic effects. Symptoms often overlap and can affect any system in the body. Infected people have reported cyclical bouts of fatigue, headaches, months of complete exhaustion, mood swings, and other symptoms. Tedros has concluded that therefore herd immunity is "morally unconscionable and unfeasible".
In terms of hospital readmissions about 9% of 106,000 individuals had to return for hospital treatment within 2 months of discharge. The average to readmit was 8 days since first hospital visit. There are several risk factors that have been identified as being a cause of multiple admissions to a hospital facility. Among these are advanced age (above 65 years of age) and presence of a chronic condition such as diabetes, COPD, heart failure or chronic kidney disease.
According to scientific reviews smokers are more likely to require intensive care or die compared to non-smokers, air pollution is similarly associated with risk factors, and pre-existing heart and lung diseases and also obesity contributes to an increased health risk of COVID-19.
It is also assumed that those that are immunocompromised are at higher risk of getting severely sick from SARS-CoV-2. One research that looked into the COVID-19 infections in hospitalized kidney transplant recipients found a mortality rate of 11%.
See also: Impact of the COVID-19 pandemic on children
Children make up a small proportion of reported cases, with about 1% of cases being under 10 years and 4% aged 10–19 years. They are likely to have milder symptoms and a lower chance of severe disease than adults. A European multinational study of hospitalized children published in The Lancet on 25 June 2020 found that about 8% of children admitted to a hospital needed intensive care. Four of those 582 children (0.7%) died, but the actual mortality rate could be "substantially lower" since milder cases that did not seek medical help were not included in the study.
Genetics also plays an important role in the ability to fight off the disease. For instance, those that do not produce detectable type I interferons or produce auto-antibodies against these may get much sicker from COVID-19. Genetic screening is able to detect interferon effector genes.
Pregnant women may be at higher risk of severe COVID-19 infection based on data from other similar viruses, like SARS and MERS, but data for COVID-19 is lacking.
COMPLICATIONS
Complications may include pneumonia, acute respiratory distress syndrome (ARDS), multi-organ failure, septic shock, and death. Cardiovascular complications may include heart failure, arrhythmias, heart inflammation, and blood clots. Approximately 20–30% of people who present with COVID-19 have elevated liver enzymes, reflecting liver injury.
Neurologic manifestations include seizure, stroke, encephalitis, and Guillain–Barré syndrome (which includes loss of motor functions). Following the infection, children may develop paediatric multisystem inflammatory syndrome, which has symptoms similar to Kawasaki disease, which can be fatal. In very rare cases, acute encephalopathy can occur, and it can be considered in those who have been diagnosed with COVID-19 and have an altered mental status.
LONGER-TERM EFFECTS
Some early studies suggest that that 10 to 20% of people with COVID-19 will experience symptoms lasting longer than a month. A majority of those who were admitted to hospital with severe disease report long-term problems, including fatigue and shortness of breath. About 5-10% of patients admitted to hospital progress to severe or critical disease, including pneumonia and acute respiratory failure.
By a variety of mechanisms, the lungs are the organs most affected in COVID-19.[228] The majority of CT scans performed show lung abnormalities in people tested after 28 days of illness.
People with advanced age, severe disease, prolonged ICU stays, or who smoke are more likely to have long lasting effects, including pulmonary fibrosis. Overall, approximately one third of those investigated after 4 weeks will have findings of pulmonary fibrosis or reduced lung function as measured by DLCO, even in people who are asymptomatic, but with the suggestion of continuing improvement with the passing of more time.
IMMUNITY
The immune response by humans to CoV-2 virus occurs as a combination of the cell-mediated immunity and antibody production, just as with most other infections. Since SARS-CoV-2 has been in the human population only since December 2019, it remains unknown if the immunity is long-lasting in people who recover from the disease. The presence of neutralizing antibodies in blood strongly correlates with protection from infection, but the level of neutralizing antibody declines with time. Those with asymptomatic or mild disease had undetectable levels of neutralizing antibody two months after infection. In another study, the level of neutralizing antibody fell 4-fold 1 to 4 months after the onset of symptoms. However, the lack of antibody in the blood does not mean antibody will not be rapidly produced upon reexposure to SARS-CoV-2. Memory B cells specific for the spike and nucleocapsid proteins of SARS-CoV-2 last for at least 6 months after appearance of symptoms. Nevertheless, 15 cases of reinfection with SARS-CoV-2 have been reported using stringent CDC criteria requiring identification of a different variant from the second infection. There are likely to be many more people who have been reinfected with the virus. Herd immunity will not eliminate the virus if reinfection is common. Some other coronaviruses circulating in people are capable of reinfection after roughly a year. Nonetheless, on 3 March 2021, scientists reported that a much more contagious Covid-19 variant, Lineage P.1, first detected in Japan, and subsequently found in Brazil, as well as in several places in the United States, may be associated with Covid-19 disease reinfection after recovery from an earlier Covid-19 infection.
MORTALITY
Several measures are commonly used to quantify mortality. These numbers vary by region and over time and are influenced by the volume of testing, healthcare system quality, treatment options, time since the initial outbreak, and population characteristics such as age, sex, and overall health. The mortality rate reflects the number of deaths within a specific demographic group divided by the population of that demographic group. Consequently, the mortality rate reflects the prevalence as well as the severity of the disease within a given population. Mortality rates are highly correlated to age, with relatively low rates for young people and relatively high rates among the elderly.
The case fatality rate (CFR) reflects the number of deaths divided by the number of diagnosed cases within a given time interval. Based on Johns Hopkins University statistics, the global death-to-case ratio is 2.2% (2,685,770/121,585,388) as of 18 March 2021. The number varies by region. The CFR may not reflect the true severity of the disease, because some infected individuals remain asymptomatic or experience only mild symptoms, and hence such infections may not be included in official case reports. Moreover, the CFR may vary markedly over time and across locations due to the availability of live virus tests.
INFECTION FATALITY RATE
A key metric in gauging the severity of COVID-19 is the infection fatality rate (IFR), also referred to as the infection fatality ratio or infection fatality risk. This metric is calculated by dividing the total number of deaths from the disease by the total number of infected individuals; hence, in contrast to the CFR, the IFR incorporates asymptomatic and undiagnosed infections as well as reported cases.
CURRENT ESTIMATES
A December 2020 systematic review and meta-analysis estimated that population IFR during the first wave of the pandemic was about 0.5% to 1% in many locations (including France, Netherlands, New Zealand, and Portugal), 1% to 2% in other locations (Australia, England, Lithuania, and Spain), and exceeded 2% in Italy. That study also found that most of these differences in IFR reflected corresponding differences in the age composition of the population and age-specific infection rates; in particular, the metaregression estimate of IFR is very low for children and younger adults (e.g., 0.002% at age 10 and 0.01% at age 25) but increases progressively to 0.4% at age 55, 1.4% at age 65, 4.6% at age 75, and 15% at age 85. These results were also highlighted in a December 2020 report issued by the WHO.
EARLIER ESTIMATES OF IFR
At an early stage of the pandemic, the World Health Organization reported estimates of IFR between 0.3% and 1%.[ On 2 July, The WHO's chief scientist reported that the average IFR estimate presented at a two-day WHO expert forum was about 0.6%. In August, the WHO found that studies incorporating data from broad serology testing in Europe showed IFR estimates converging at approximately 0.5–1%. Firm lower limits of IFRs have been established in a number of locations such as New York City and Bergamo in Italy since the IFR cannot be less than the population fatality rate. As of 10 July, in New York City, with a population of 8.4 million, 23,377 individuals (18,758 confirmed and 4,619 probable) have died with COVID-19 (0.3% of the population).Antibody testing in New York City suggested an IFR of ~0.9%,[258] and ~1.4%. In Bergamo province, 0.6% of the population has died. In September 2020 the U.S. Center for Disease Control & Prevention reported preliminary estimates of age-specific IFRs for public health planning purposes.
SEX DIFFERENCES
Early reviews of epidemiologic data showed gendered impact of the pandemic and a higher mortality rate in men in China and Italy. The Chinese Center for Disease Control and Prevention reported the death rate was 2.8% for men and 1.7% for women. Later reviews in June 2020 indicated that there is no significant difference in susceptibility or in CFR between genders. One review acknowledges the different mortality rates in Chinese men, suggesting that it may be attributable to lifestyle choices such as smoking and drinking alcohol rather than genetic factors. Sex-based immunological differences, lesser prevalence of smoking in women and men developing co-morbid conditions such as hypertension at a younger age than women could have contributed to the higher mortality in men. In Europe, 57% of the infected people were men and 72% of those died with COVID-19 were men. As of April 2020, the US government is not tracking sex-related data of COVID-19 infections. Research has shown that viral illnesses like Ebola, HIV, influenza and SARS affect men and women differently.
ETHNIC DIFFERENCES
In the US, a greater proportion of deaths due to COVID-19 have occurred among African Americans and other minority groups. Structural factors that prevent them from practicing social distancing include their concentration in crowded substandard housing and in "essential" occupations such as retail grocery workers, public transit employees, health-care workers and custodial staff. Greater prevalence of lacking health insurance and care and of underlying conditions such as diabetes, hypertension and heart disease also increase their risk of death. Similar issues affect Native American and Latino communities. According to a US health policy non-profit, 34% of American Indian and Alaska Native People (AIAN) non-elderly adults are at risk of serious illness compared to 21% of white non-elderly adults. The source attributes it to disproportionately high rates of many health conditions that may put them at higher risk as well as living conditions like lack of access to clean water. Leaders have called for efforts to research and address the disparities. In the U.K., a greater proportion of deaths due to COVID-19 have occurred in those of a Black, Asian, and other ethnic minority background. More severe impacts upon victims including the relative incidence of the necessity of hospitalization requirements, and vulnerability to the disease has been associated via DNA analysis to be expressed in genetic variants at chromosomal region 3, features that are associated with European Neanderthal heritage. That structure imposes greater risks that those affected will develop a more severe form of the disease. The findings are from Professor Svante Pääbo and researchers he leads at the Max Planck Institute for Evolutionary Anthropology and the Karolinska Institutet. This admixture of modern human and Neanderthal genes is estimated to have occurred roughly between 50,000 and 60,000 years ago in Southern Europe.
COMORBIDITIES
Most of those who die of COVID-19 have pre-existing (underlying) conditions, including hypertension, diabetes mellitus, and cardiovascular disease. According to March data from the United States, 89% of those hospitalised had preexisting conditions. The Italian Istituto Superiore di Sanità reported that out of 8.8% of deaths where medical charts were available, 96.1% of people had at least one comorbidity with the average person having 3.4 diseases. According to this report the most common comorbidities are hypertension (66% of deaths), type 2 diabetes (29.8% of deaths), Ischemic Heart Disease (27.6% of deaths), atrial fibrillation (23.1% of deaths) and chronic renal failure (20.2% of deaths).
Most critical respiratory comorbidities according to the CDC, are: moderate or severe asthma, pre-existing COPD, pulmonary fibrosis, cystic fibrosis. Evidence stemming from meta-analysis of several smaller research papers also suggests that smoking can be associated with worse outcomes. When someone with existing respiratory problems is infected with COVID-19, they might be at greater risk for severe symptoms. COVID-19 also poses a greater risk to people who misuse opioids and methamphetamines, insofar as their drug use may have caused lung damage.
In August 2020 the CDC issued a caution that tuberculosis infections could increase the risk of severe illness or death. The WHO recommended that people with respiratory symptoms be screened for both diseases, as testing positive for COVID-19 couldn't rule out co-infections. Some projections have estimated that reduced TB detection due to the pandemic could result in 6.3 million additional TB cases and 1.4 million TB related deaths by 2025.
NAME
During the initial outbreak in Wuhan, China, the virus and disease were commonly referred to as "coronavirus" and "Wuhan coronavirus", with the disease sometimes called "Wuhan pneumonia". In the past, many diseases have been named after geographical locations, such as the Spanish flu, Middle East Respiratory Syndrome, and Zika virus. In January 2020, the WHO recommended 2019-nCov and 2019-nCoV acute respiratory disease as interim names for the virus and disease per 2015 guidance and international guidelines against using geographical locations (e.g. Wuhan, China), animal species, or groups of people in disease and virus names in part to prevent social stigma. The official names COVID-19 and SARS-CoV-2 were issued by the WHO on 11 February 2020. Tedros Adhanom explained: CO for corona, VI for virus, D for disease and 19 for when the outbreak was first identified (31 December 2019). The WHO additionally uses "the COVID-19 virus" and "the virus responsible for COVID-19" in public communications.
HISTORY
The virus is thought to be natural and of an animal origin, through spillover infection. There are several theories about where the first case (the so-called patient zero) originated. Phylogenetics estimates that SARS-CoV-2 arose in October or November 2019. Evidence suggests that it descends from a coronavirus that infects wild bats, and spread to humans through an intermediary wildlife host.
The first known human infections were in Wuhan, Hubei, China. A study of the first 41 cases of confirmed COVID-19, published in January 2020 in The Lancet, reported the earliest date of onset of symptoms as 1 December 2019.Official publications from the WHO reported the earliest onset of symptoms as 8 December 2019. Human-to-human transmission was confirmed by the WHO and Chinese authorities by 20 January 2020. According to official Chinese sources, these were mostly linked to the Huanan Seafood Wholesale Market, which also sold live animals. In May 2020 George Gao, the director of the CDC, said animal samples collected from the seafood market had tested negative for the virus, indicating that the market was the site of an early superspreading event, but that it was not the site of the initial outbreak.[ Traces of the virus have been found in wastewater samples that were collected in Milan and Turin, Italy, on 18 December 2019.
By December 2019, the spread of infection was almost entirely driven by human-to-human transmission. The number of coronavirus cases in Hubei gradually increased, reaching 60 by 20 December, and at least 266 by 31 December. On 24 December, Wuhan Central Hospital sent a bronchoalveolar lavage fluid (BAL) sample from an unresolved clinical case to sequencing company Vision Medicals. On 27 and 28 December, Vision Medicals informed the Wuhan Central Hospital and the Chinese CDC of the results of the test, showing a new coronavirus. A pneumonia cluster of unknown cause was observed on 26 December and treated by the doctor Zhang Jixian in Hubei Provincial Hospital, who informed the Wuhan Jianghan CDC on 27 December. On 30 December, a test report addressed to Wuhan Central Hospital, from company CapitalBio Medlab, stated an erroneous positive result for SARS, causing a group of doctors at Wuhan Central Hospital to alert their colleagues and relevant hospital authorities of the result. The Wuhan Municipal Health Commission issued a notice to various medical institutions on "the treatment of pneumonia of unknown cause" that same evening. Eight of these doctors, including Li Wenliang (punished on 3 January), were later admonished by the police for spreading false rumours and another, Ai Fen, was reprimanded by her superiors for raising the alarm.
The Wuhan Municipal Health Commission made the first public announcement of a pneumonia outbreak of unknown cause on 31 December, confirming 27 cases—enough to trigger an investigation.
During the early stages of the outbreak, the number of cases doubled approximately every seven and a half days. In early and mid-January 2020, the virus spread to other Chinese provinces, helped by the Chinese New Year migration and Wuhan being a transport hub and major rail interchange. On 20 January, China reported nearly 140 new cases in one day, including two people in Beijing and one in Shenzhen. Later official data shows 6,174 people had already developed symptoms by then, and more may have been infected. A report in The Lancet on 24 January indicated human transmission, strongly recommended personal protective equipment for health workers, and said testing for the virus was essential due to its "pandemic potential". On 30 January, the WHO declared the coronavirus a Public Health Emergency of International Concern. By this time, the outbreak spread by a factor of 100 to 200 times.
Italy had its first confirmed cases on 31 January 2020, two tourists from China. As of 13 March 2020 the WHO considered Europe the active centre of the pandemic. Italy overtook China as the country with the most deaths on 19 March 2020. By 26 March the United States had overtaken China and Italy with the highest number of confirmed cases in the world. Research on coronavirus genomes indicates the majority of COVID-19 cases in New York came from European travellers, rather than directly from China or any other Asian country. Retesting of prior samples found a person in France who had the virus on 27 December 2019, and a person in the United States who died from the disease on 6 February 2020.
After 55 days without a locally transmitted case, Beijing reported a new COVID-19 case on 11 June 2020 which was followed by two more cases on 12 June. By 15 June there were 79 cases officially confirmed, most of them were people that went to Xinfadi Wholesale Market.
RT-PCR testing of untreated wastewater samples from Brazil and Italy have suggested detection of SARS-CoV-2 as early as November and December 2019, respectively, but the methods of such sewage studies have not been optimised, many have not been peer reviewed, details are often missing, and there is a risk of false positives due to contamination or if only one gene target is detected. A September 2020 review journal article said, "The possibility that the COVID-19 infection had already spread to Europe at the end of last year is now indicated by abundant, even if partially circumstantial, evidence", including pneumonia case numbers and radiology in France and Italy in November and December.
MISINFORMATION
After the initial outbreak of COVID-19, misinformation and disinformation regarding the origin, scale, prevention, treatment, and other aspects of the disease rapidly spread online.
In September 2020, the U.S. CDC published preliminary estimates of the risk of death by age groups in the United States, but those estimates were widely misreported and misunderstood.
OTHER ANIMALS
Humans appear to be capable of spreading the virus to some other animals, a type of disease transmission referred to as zooanthroponosis.
Some pets, especially cats and ferrets, can catch this virus from infected humans. Symptoms in cats include respiratory (such as a cough) and digestive symptoms. Cats can spread the virus to other cats, and may be able to spread the virus to humans, but cat-to-human transmission of SARS-CoV-2 has not been proven. Compared to cats, dogs are less susceptible to this infection. Behaviors which increase the risk of transmission include kissing, licking, and petting the animal.
The virus does not appear to be able to infect pigs, ducks, or chickens at all.[ Mice, rats, and rabbits, if they can be infected at all, are unlikely to be involved in spreading the virus.
Tigers and lions in zoos have become infected as a result of contact with infected humans. As expected, monkeys and great ape species such as orangutans can also be infected with the COVID-19 virus.
Minks, which are in the same family as ferrets, have been infected. Minks may be asymptomatic, and can also spread the virus to humans. Multiple countries have identified infected animals in mink farms. Denmark, a major producer of mink pelts, ordered the slaughter of all minks over fears of viral mutations. A vaccine for mink and other animals is being researched.
RESEARCH
International research on vaccines and medicines in COVID-19 is underway by government organisations, academic groups, and industry researchers. The CDC has classified it to require a BSL3 grade laboratory. There has been a great deal of COVID-19 research, involving accelerated research processes and publishing shortcuts to meet the global demand.
As of December 2020, hundreds of clinical trials have been undertaken, with research happening on every continent except Antarctica. As of November 2020, more than 200 possible treatments had been studied in humans so far.
Transmission and prevention research
Modelling research has been conducted with several objectives, including predictions of the dynamics of transmission, diagnosis and prognosis of infection, estimation of the impact of interventions, or allocation of resources. Modelling studies are mostly based on epidemiological models, estimating the number of infected people over time under given conditions. Several other types of models have been developed and used during the COVID-19 including computational fluid dynamics models to study the flow physics of COVID-19, retrofits of crowd movement models to study occupant exposure, mobility-data based models to investigate transmission, or the use of macroeconomic models to assess the economic impact of the pandemic. Further, conceptual frameworks from crisis management research have been applied to better understand the effects of COVID-19 on organizations worldwide.
TREATMENT-RELATED RESEARCH
Repurposed antiviral drugs make up most of the research into COVID-19 treatments. Other candidates in trials include vasodilators, corticosteroids, immune therapies, lipoic acid, bevacizumab, and recombinant angiotensin-converting enzyme 2.
In March 2020, the World Health Organization (WHO) initiated the Solidarity trial to assess the treatment effects of some promising drugs: an experimental drug called remdesivir; anti-malarial drugs chloroquine and hydroxychloroquine; two anti-HIV drugs, lopinavir/ritonavir; and interferon-beta. More than 300 active clinical trials were underway as of April 2020.
Research on the antimalarial drugs hydroxychloroquine and chloroquine showed that they were ineffective at best, and that they may reduce the antiviral activity of remdesivir. By May 2020, France, Italy, and Belgium had banned the use of hydroxychloroquine as a COVID-19 treatment.
In June, initial results from the randomised RECOVERY Trial in the United Kingdom showed that dexamethasone reduced mortality by one third for people who are critically ill on ventilators and one fifth for those receiving supplemental oxygen. Because this is a well-tested and widely available treatment, it was welcomed by the WHO, which is in the process of updating treatment guidelines to include dexamethasone and other steroids. Based on those preliminary results, dexamethasone treatment has been recommended by the NIH for patients with COVID-19 who are mechanically ventilated or who require supplemental oxygen but not in patients with COVID-19 who do not require supplemental oxygen.
In September 2020, the WHO released updated guidance on using corticosteroids for COVID-19. The WHO recommends systemic corticosteroids rather than no systemic corticosteroids for the treatment of people with severe and critical COVID-19 (strong recommendation, based on moderate certainty evidence). The WHO suggests not to use corticosteroids in the treatment of people with non-severe COVID-19 (conditional recommendation, based on low certainty evidence). The updated guidance was based on a meta-analysis of clinical trials of critically ill COVID-19 patients.
WIKIPEDIA
Coronavirus disease 2019 (COVID-19) is a contagious disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The first case was identified in Wuhan, China, in December 2019. The disease has since spread worldwide, leading to an ongoing pandemic.
Symptoms of COVID-19 are variable, but often include fever, cough, fatigue, breathing difficulties, and loss of smell and taste. Symptoms begin one to fourteen days after exposure to the virus. Of those people who develop noticeable symptoms, most (81%) develop mild to moderate symptoms (up to mild pneumonia), while 14% develop severe symptoms (dyspnea, hypoxia, or more than 50% lung involvement on imaging), and 5% suffer critical symptoms (respiratory failure, shock, or multiorgan dysfunction). Older people are more likely to have severe symptoms. At least a third of the people who are infected with the virus remain asymptomatic and do not develop noticeable symptoms at any point in time, but they still can spread the disease.[ Around 20% of those people will remain asymptomatic throughout infection, and the rest will develop symptoms later on, becoming pre-symptomatic rather than asymptomatic and therefore having a higher risk of transmitting the virus to others. Some people continue to experience a range of effects—known as long COVID—for months after recovery, and damage to organs has been observed. Multi-year studies are underway to further investigate the long-term effects of the disease.
The virus that causes COVID-19 spreads mainly when an infected person is in close contact[a] with another person. Small droplets and aerosols containing the virus can spread from an infected person's nose and mouth as they breathe, cough, sneeze, sing, or speak. Other people are infected if the virus gets into their mouth, nose or eyes. The virus may also spread via contaminated surfaces, although this is not thought to be the main route of transmission. The exact route of transmission is rarely proven conclusively, but infection mainly happens when people are near each other for long enough. People who are infected can transmit the virus to another person up to two days before they themselves show symptoms, as can people who do not experience symptoms. People remain infectious for up to ten days after the onset of symptoms in moderate cases and up to 20 days in severe cases. Several testing methods have been developed to diagnose the disease. The standard diagnostic method is by detection of the virus' nucleic acid by real-time reverse transcription polymerase chain reaction (rRT-PCR), transcription-mediated amplification (TMA), or by reverse transcription loop-mediated isothermal amplification (RT-LAMP) from a nasopharyngeal swab.
Preventive measures include physical or social distancing, quarantining, ventilation of indoor spaces, covering coughs and sneezes, hand washing, and keeping unwashed hands away from the face. The use of face masks or coverings has been recommended in public settings to minimise the risk of transmissions. Several vaccines have been developed and several countries have initiated mass vaccination campaigns.
Although work is underway to develop drugs that inhibit the virus, the primary treatment is currently symptomatic. Management involves the treatment of symptoms, supportive care, isolation, and experimental measures.
SIGNS AND SYSTOMS
Symptoms of COVID-19 are variable, ranging from mild symptoms to severe illness. Common symptoms include headache, loss of smell and taste, nasal congestion and rhinorrhea, cough, muscle pain, sore throat, fever, diarrhea, and breathing difficulties. People with the same infection may have different symptoms, and their symptoms may change over time. Three common clusters of symptoms have been identified: one respiratory symptom cluster with cough, sputum, shortness of breath, and fever; a musculoskeletal symptom cluster with muscle and joint pain, headache, and fatigue; a cluster of digestive symptoms with abdominal pain, vomiting, and diarrhea. In people without prior ear, nose, and throat disorders, loss of taste combined with loss of smell is associated with COVID-19.
Most people (81%) develop mild to moderate symptoms (up to mild pneumonia), while 14% develop severe symptoms (dyspnea, hypoxia, or more than 50% lung involvement on imaging) and 5% of patients suffer critical symptoms (respiratory failure, shock, or multiorgan dysfunction). At least a third of the people who are infected with the virus do not develop noticeable symptoms at any point in time. These asymptomatic carriers tend not to get tested and can spread the disease. Other infected people will develop symptoms later, called "pre-symptomatic", or have very mild symptoms and can also spread the virus.
As is common with infections, there is a delay between the moment a person first becomes infected and the appearance of the first symptoms. The median delay for COVID-19 is four to five days. Most symptomatic people experience symptoms within two to seven days after exposure, and almost all will experience at least one symptom within 12 days.
Most people recover from the acute phase of the disease. However, some people continue to experience a range of effects for months after recovery—named long COVID—and damage to organs has been observed. Multi-year studies are underway to further investigate the long-term effects of the disease.
CAUSE
TRANSMISSION
Coronavirus disease 2019 (COVID-19) spreads from person to person mainly through the respiratory route after an infected person coughs, sneezes, sings, talks or breathes. A new infection occurs when virus-containing particles exhaled by an infected person, either respiratory droplets or aerosols, get into the mouth, nose, or eyes of other people who are in close contact with the infected person. During human-to-human transmission, an average 1000 infectious SARS-CoV-2 virions are thought to initiate a new infection.
The closer people interact, and the longer they interact, the more likely they are to transmit COVID-19. Closer distances can involve larger droplets (which fall to the ground) and aerosols, whereas longer distances only involve aerosols. Larger droplets can also turn into aerosols (known as droplet nuclei) through evaporation. The relative importance of the larger droplets and the aerosols is not clear as of November 2020; however, the virus is not known to spread between rooms over long distances such as through air ducts. Airborne transmission is able to particularly occur indoors, in high risk locations such as restaurants, choirs, gyms, nightclubs, offices, and religious venues, often when they are crowded or less ventilated. It also occurs in healthcare settings, often when aerosol-generating medical procedures are performed on COVID-19 patients.
Although it is considered possible there is no direct evidence of the virus being transmitted by skin to skin contact. A person could get COVID-19 indirectly by touching a contaminated surface or object before touching their own mouth, nose, or eyes, though this is not thought to be the main way the virus spreads. The virus is not known to spread through feces, urine, breast milk, food, wastewater, drinking water, or via animal disease vectors (although some animals can contract the virus from humans). It very rarely transmits from mother to baby during pregnancy.
Social distancing and the wearing of cloth face masks, surgical masks, respirators, or other face coverings are controls for droplet transmission. Transmission may be decreased indoors with well maintained heating and ventilation systems to maintain good air circulation and increase the use of outdoor air.
The number of people generally infected by one infected person varies. Coronavirus disease 2019 is more infectious than influenza, but less so than measles. It often spreads in clusters, where infections can be traced back to an index case or geographical location. There is a major role of "super-spreading events", where many people are infected by one person.
A person who is infected can transmit the virus to others up to two days before they themselves show symptoms, and even if symptoms never appear. People remain infectious in moderate cases for 7–12 days, and up to two weeks in severe cases. In October 2020, medical scientists reported evidence of reinfection in one person.
VIROLOGY
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a novel severe acute respiratory syndrome coronavirus. It was first isolated from three people with pneumonia connected to the cluster of acute respiratory illness cases in Wuhan. All structural features of the novel SARS-CoV-2 virus particle occur in related coronaviruses in nature.
Outside the human body, the virus is destroyed by household soap, which bursts its protective bubble.
SARS-CoV-2 is closely related to the original SARS-CoV. It is thought to have an animal (zoonotic) origin. Genetic analysis has revealed that the coronavirus genetically clusters with the genus Betacoronavirus, in subgenus Sarbecovirus (lineage B) together with two bat-derived strains. It is 96% identical at the whole genome level to other bat coronavirus samples (BatCov RaTG13). The structural proteins of SARS-CoV-2 include membrane glycoprotein (M), envelope protein (E), nucleocapsid protein (N), and the spike protein (S). The M protein of SARS-CoV-2 is about 98% similar to the M protein of bat SARS-CoV, maintains around 98% homology with pangolin SARS-CoV, and has 90% homology with the M protein of SARS-CoV; whereas, the similarity is only around 38% with the M protein of MERS-CoV. The structure of the M protein resembles the sugar transporter SemiSWEET.
The many thousands of SARS-CoV-2 variants are grouped into clades. Several different clade nomenclatures have been proposed. Nextstrain divides the variants into five clades (19A, 19B, 20A, 20B, and 20C), while GISAID divides them into seven (L, O, V, S, G, GH, and GR).
Several notable variants of SARS-CoV-2 emerged in late 2020. Cluster 5 emerged among minks and mink farmers in Denmark. After strict quarantines and a mink euthanasia campaign, it is believed to have been eradicated. The Variant of Concern 202012/01 (VOC 202012/01) is believed to have emerged in the United Kingdom in September. The 501Y.V2 Variant, which has the same N501Y mutation, arose independently in South Africa.
SARS-CoV-2 VARIANTS
Three known variants of SARS-CoV-2 are currently spreading among global populations as of January 2021 including the UK Variant (referred to as B.1.1.7) first found in London and Kent, a variant discovered in South Africa (referred to as 1.351), and a variant discovered in Brazil (referred to as P.1).
Using Whole Genome Sequencing, epidemiology and modelling suggest the new UK variant ‘VUI – 202012/01’ (the first Variant Under Investigation in December 2020) transmits more easily than other strains.
PATHOPHYSIOLOGY
COVID-19 can affect the upper respiratory tract (sinuses, nose, and throat) and the lower respiratory tract (windpipe and lungs). The lungs are the organs most affected by COVID-19 because the virus accesses host cells via the enzyme angiotensin-converting enzyme 2 (ACE2), which is most abundant in type II alveolar cells of the lungs. The virus uses a special surface glycoprotein called a "spike" (peplomer) to connect to ACE2 and enter the host cell. The density of ACE2 in each tissue correlates with the severity of the disease in that tissue and decreasing ACE2 activity might be protective, though another view is that increasing ACE2 using angiotensin II receptor blocker medications could be protective. As the alveolar disease progresses, respiratory failure might develop and death may follow.
Whether SARS-CoV-2 is able to invade the nervous system remains unknown. The virus is not detected in the CNS of the majority of COVID-19 people with neurological issues. However, SARS-CoV-2 has been detected at low levels in the brains of those who have died from COVID-19, but these results need to be confirmed. SARS-CoV-2 could cause respiratory failure through affecting the brain stem as other coronaviruses have been found to invade the CNS. While virus has been detected in cerebrospinal fluid of autopsies, the exact mechanism by which it invades the CNS remains unclear and may first involve invasion of peripheral nerves given the low levels of ACE2 in the brain. The virus may also enter the bloodstream from the lungs and cross the blood-brain barrier to gain access to the CNS, possibly within an infected white blood cell.
The virus also affects gastrointestinal organs as ACE2 is abundantly expressed in the glandular cells of gastric, duodenal and rectal epithelium as well as endothelial cells and enterocytes of the small intestine.
The virus can cause acute myocardial injury and chronic damage to the cardiovascular system. An acute cardiac injury was found in 12% of infected people admitted to the hospital in Wuhan, China, and is more frequent in severe disease. Rates of cardiovascular symptoms are high, owing to the systemic inflammatory response and immune system disorders during disease progression, but acute myocardial injuries may also be related to ACE2 receptors in the heart. ACE2 receptors are highly expressed in the heart and are involved in heart function. A high incidence of thrombosis and venous thromboembolism have been found people transferred to Intensive care unit (ICU) with COVID-19 infections, and may be related to poor prognosis. Blood vessel dysfunction and clot formation (as suggested by high D-dimer levels caused by blood clots) are thought to play a significant role in mortality, incidences of clots leading to pulmonary embolisms, and ischaemic events within the brain have been noted as complications leading to death in people infected with SARS-CoV-2. Infection appears to set off a chain of vasoconstrictive responses within the body, constriction of blood vessels within the pulmonary circulation has also been posited as a mechanism in which oxygenation decreases alongside the presentation of viral pneumonia. Furthermore, microvascular blood vessel damage has been reported in a small number of tissue samples of the brains – without detected SARS-CoV-2 – and the olfactory bulbs from those who have died from COVID-19.
Another common cause of death is complications related to the kidneys. Early reports show that up to 30% of hospitalized patients both in China and in New York have experienced some injury to their kidneys, including some persons with no previous kidney problems.
Autopsies of people who died of COVID-19 have found diffuse alveolar damage, and lymphocyte-containing inflammatory infiltrates within the lung.
IMMUNOPATHOLOGY
Although SARS-CoV-2 has a tropism for ACE2-expressing epithelial cells of the respiratory tract, people with severe COVID-19 have symptoms of systemic hyperinflammation. Clinical laboratory findings of elevated IL-2, IL-7, IL-6, granulocyte-macrophage colony-stimulating factor (GM-CSF), interferon-γ inducible protein 10 (IP-10), monocyte chemoattractant protein 1 (MCP-1), macrophage inflammatory protein 1-α (MIP-1α), and tumour necrosis factor-α (TNF-α) indicative of cytokine release syndrome (CRS) suggest an underlying immunopathology.
Additionally, people with COVID-19 and acute respiratory distress syndrome (ARDS) have classical serum biomarkers of CRS, including elevated C-reactive protein (CRP), lactate dehydrogenase (LDH), D-dimer, and ferritin.
Systemic inflammation results in vasodilation, allowing inflammatory lymphocytic and monocytic infiltration of the lung and the heart. In particular, pathogenic GM-CSF-secreting T-cells were shown to correlate with the recruitment of inflammatory IL-6-secreting monocytes and severe lung pathology in people with COVID-19 . Lymphocytic infiltrates have also been reported at autopsy.
VIRAL AND HOST FACTORS
VIRUS PROTEINS
Multiple viral and host factors affect the pathogenesis of the virus. The S-protein, otherwise known as the spike protein, is the viral component that attaches to the host receptor via the ACE2 receptors. It includes two subunits: S1 and S2. S1 determines the virus host range and cellular tropism via the receptor binding domain. S2 mediates the membrane fusion of the virus to its potential cell host via the H1 and HR2, which are heptad repeat regions. Studies have shown that S1 domain induced IgG and IgA antibody levels at a much higher capacity. It is the focus spike proteins expression that are involved in many effective COVID-19 vaccines.
The M protein is the viral protein responsible for the transmembrane transport of nutrients. It is the cause of the bud release and the formation of the viral envelope. The N and E protein are accessory proteins that interfere with the host's immune response.
HOST FACTORS
Human angiotensin converting enzyme 2 (hACE2) is the host factor that SARS-COV2 virus targets causing COVID-19. Theoretically the usage of angiotensin receptor blockers (ARB) and ACE inhibitors upregulating ACE2 expression might increase morbidity with COVID-19, though animal data suggest some potential protective effect of ARB. However no clinical studies have proven susceptibility or outcomes. Until further data is available, guidelines and recommendations for hypertensive patients remain.
The virus' effect on ACE2 cell surfaces leads to leukocytic infiltration, increased blood vessel permeability, alveolar wall permeability, as well as decreased secretion of lung surfactants. These effects cause the majority of the respiratory symptoms. However, the aggravation of local inflammation causes a cytokine storm eventually leading to a systemic inflammatory response syndrome.
HOST CYTOKINE RESPONSE
The severity of the inflammation can be attributed to the severity of what is known as the cytokine storm. Levels of interleukin 1B, interferon-gamma, interferon-inducible protein 10, and monocyte chemoattractant protein 1 were all associated with COVID-19 disease severity. Treatment has been proposed to combat the cytokine storm as it remains to be one of the leading causes of morbidity and mortality in COVID-19 disease.
A cytokine storm is due to an acute hyperinflammatory response that is responsible for clinical illness in an array of diseases but in COVID-19, it is related to worse prognosis and increased fatality. The storm causes the acute respiratory distress syndrome, blood clotting events such as strokes, myocardial infarction, encephalitis, acute kidney injury, and vasculitis. The production of IL-1, IL-2, IL-6, TNF-alpha, and interferon-gamma, all crucial components of normal immune responses, inadvertently become the causes of a cytokine storm. The cells of the central nervous system, the microglia, neurons, and astrocytes, are also be involved in the release of pro-inflammatory cytokines affecting the nervous system, and effects of cytokine storms toward the CNS are not uncommon.
DIAGNOSIS
COVID-19 can provisionally be diagnosed on the basis of symptoms and confirmed using reverse transcription polymerase chain reaction (RT-PCR) or other nucleic acid testing of infected secretions. Along with laboratory testing, chest CT scans may be helpful to diagnose COVID-19 in individuals with a high clinical suspicion of infection. Detection of a past infection is possible with serological tests, which detect antibodies produced by the body in response to the infection.
VIRAL TESTING
The standard methods of testing for presence of SARS-CoV-2 are nucleic acid tests, which detects the presence of viral RNA fragments. As these tests detect RNA but not infectious virus, its "ability to determine duration of infectivity of patients is limited." The test is typically done on respiratory samples obtained by a nasopharyngeal swab; however, a nasal swab or sputum sample may also be used. Results are generally available within hours. The WHO has published several testing protocols for the disease.
A number of laboratories and companies have developed serological tests, which detect antibodies produced by the body in response to infection. Several have been evaluated by Public Health England and approved for use in the UK.
The University of Oxford's CEBM has pointed to mounting evidence that "a good proportion of 'new' mild cases and people re-testing positives after quarantine or discharge from hospital are not infectious, but are simply clearing harmless virus particles which their immune system has efficiently dealt with" and have called for "an international effort to standardize and periodically calibrate testing" On 7 September, the UK government issued "guidance for procedures to be implemented in laboratories to provide assurance of positive SARS-CoV-2 RNA results during periods of low prevalence, when there is a reduction in the predictive value of positive test results."
IMAGING
Chest CT scans may be helpful to diagnose COVID-19 in individuals with a high clinical suspicion of infection but are not recommended for routine screening. Bilateral multilobar ground-glass opacities with a peripheral, asymmetric, and posterior distribution are common in early infection. Subpleural dominance, crazy paving (lobular septal thickening with variable alveolar filling), and consolidation may appear as the disease progresses. Characteristic imaging features on chest radiographs and computed tomography (CT) of people who are symptomatic include asymmetric peripheral ground-glass opacities without pleural effusions.
Many groups have created COVID-19 datasets that include imagery such as the Italian Radiological Society which has compiled an international online database of imaging findings for confirmed cases. Due to overlap with other infections such as adenovirus, imaging without confirmation by rRT-PCR is of limited specificity in identifying COVID-19. A large study in China compared chest CT results to PCR and demonstrated that though imaging is less specific for the infection, it is faster and more sensitive.
Coding
In late 2019, the WHO assigned emergency ICD-10 disease codes U07.1 for deaths from lab-confirmed SARS-CoV-2 infection and U07.2 for deaths from clinically or epidemiologically diagnosed COVID-19 without lab-confirmed SARS-CoV-2 infection.
PATHOLOGY
The main pathological findings at autopsy are:
Macroscopy: pericarditis, lung consolidation and pulmonary oedema
Lung findings:
minor serous exudation, minor fibrin exudation
pulmonary oedema, pneumocyte hyperplasia, large atypical pneumocytes, interstitial inflammation with lymphocytic infiltration and multinucleated giant cell formation
diffuse alveolar damage (DAD) with diffuse alveolar exudates. DAD is the cause of acute respiratory distress syndrome (ARDS) and severe hypoxemia.
organisation of exudates in alveolar cavities and pulmonary interstitial fibrosis
plasmocytosis in BAL
Blood: disseminated intravascular coagulation (DIC); leukoerythroblastic reaction
Liver: microvesicular steatosis
PREVENTION
Preventive measures to reduce the chances of infection include staying at home, wearing a mask in public, avoiding crowded places, keeping distance from others, ventilating indoor spaces, washing hands with soap and water often and for at least 20 seconds, practising good respiratory hygiene, and avoiding touching the eyes, nose, or mouth with unwashed hands.
Those diagnosed with COVID-19 or who believe they may be infected are advised by the CDC to stay home except to get medical care, call ahead before visiting a healthcare provider, wear a face mask before entering the healthcare provider's office and when in any room or vehicle with another person, cover coughs and sneezes with a tissue, regularly wash hands with soap and water and avoid sharing personal household items.
The first COVID-19 vaccine was granted regulatory approval on 2 December by the UK medicines regulator MHRA. It was evaluated for emergency use authorization (EUA) status by the US FDA, and in several other countries. Initially, the US National Institutes of Health guidelines do not recommend any medication for prevention of COVID-19, before or after exposure to the SARS-CoV-2 virus, outside the setting of a clinical trial. Without a vaccine, other prophylactic measures, or effective treatments, a key part of managing COVID-19 is trying to decrease and delay the epidemic peak, known as "flattening the curve". This is done by slowing the infection rate to decrease the risk of health services being overwhelmed, allowing for better treatment of current cases, and delaying additional cases until effective treatments or a vaccine become available.
VACCINE
A COVID‑19 vaccine is a vaccine intended to provide acquired immunity against severe acute respiratory syndrome coronavirus 2 (SARS‑CoV‑2), the virus causing coronavirus disease 2019 (COVID‑19). Prior to the COVID‑19 pandemic, there was an established body of knowledge about the structure and function of coronaviruses causing diseases like severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS), which enabled accelerated development of various vaccine technologies during early 2020. On 10 January 2020, the SARS-CoV-2 genetic sequence data was shared through GISAID, and by 19 March, the global pharmaceutical industry announced a major commitment to address COVID-19.
In Phase III trials, several COVID‑19 vaccines have demonstrated efficacy as high as 95% in preventing symptomatic COVID‑19 infections. As of March 2021, 12 vaccines were authorized by at least one national regulatory authority for public use: two RNA vaccines (the Pfizer–BioNTech vaccine and the Moderna vaccine), four conventional inactivated vaccines (BBIBP-CorV, CoronaVac, Covaxin, and CoviVac), four viral vector vaccines (Sputnik V, the Oxford–AstraZeneca vaccine, Convidicea, and the Johnson & Johnson vaccine), and two protein subunit vaccines (EpiVacCorona and RBD-Dimer). In total, as of March 2021, 308 vaccine candidates were in various stages of development, with 73 in clinical research, including 24 in Phase I trials, 33 in Phase I–II trials, and 16 in Phase III development.
Many countries have implemented phased distribution plans that prioritize those at highest risk of complications, such as the elderly, and those at high risk of exposure and transmission, such as healthcare workers. As of 17 March 2021, 400.22 million doses of COVID‑19 vaccine have been administered worldwide based on official reports from national health agencies. AstraZeneca-Oxford anticipates producing 3 billion doses in 2021, Pfizer-BioNTech 1.3 billion doses, and Sputnik V, Sinopharm, Sinovac, and Johnson & Johnson 1 billion doses each. Moderna targets producing 600 million doses and Convidicea 500 million doses in 2021. By December 2020, more than 10 billion vaccine doses had been preordered by countries, with about half of the doses purchased by high-income countries comprising 14% of the world's population.
SOCIAL DISTANCING
Social distancing (also known as physical distancing) includes infection control actions intended to slow the spread of the disease by minimising close contact between individuals. Methods include quarantines; travel restrictions; and the closing of schools, workplaces, stadiums, theatres, or shopping centres. Individuals may apply social distancing methods by staying at home, limiting travel, avoiding crowded areas, using no-contact greetings, and physically distancing themselves from others. Many governments are now mandating or recommending social distancing in regions affected by the outbreak.
Outbreaks have occurred in prisons due to crowding and an inability to enforce adequate social distancing. In the United States, the prisoner population is aging and many of them are at high risk for poor outcomes from COVID-19 due to high rates of coexisting heart and lung disease, and poor access to high-quality healthcare.
SELF-ISOLATION
Self-isolation at home has been recommended for those diagnosed with COVID-19 and those who suspect they have been infected. Health agencies have issued detailed instructions for proper self-isolation. Many governments have mandated or recommended self-quarantine for entire populations. The strongest self-quarantine instructions have been issued to those in high-risk groups. Those who may have been exposed to someone with COVID-19 and those who have recently travelled to a country or region with the widespread transmission have been advised to self-quarantine for 14 days from the time of last possible exposure.
Face masks and respiratory hygiene
The WHO and the US CDC recommend individuals wear non-medical face coverings in public settings where there is an increased risk of transmission and where social distancing measures are difficult to maintain. This recommendation is meant to reduce the spread of the disease by asymptomatic and pre-symptomatic individuals and is complementary to established preventive measures such as social distancing. Face coverings limit the volume and travel distance of expiratory droplets dispersed when talking, breathing, and coughing. A face covering without vents or holes will also filter out particles containing the virus from inhaled and exhaled air, reducing the chances of infection. But, if the mask include an exhalation valve, a wearer that is infected (maybe without having noticed that, and asymptomatic) would transmit the virus outwards through it, despite any certification they can have. So the masks with exhalation valve are not for the infected wearers, and are not reliable to stop the pandemic in a large scale. Many countries and local jurisdictions encourage or mandate the use of face masks or cloth face coverings by members of the public to limit the spread of the virus.
Masks are also strongly recommended for those who may have been infected and those taking care of someone who may have the disease. When not wearing a mask, the CDC recommends covering the mouth and nose with a tissue when coughing or sneezing and recommends using the inside of the elbow if no tissue is available. Proper hand hygiene after any cough or sneeze is encouraged. Healthcare professionals interacting directly with people who have COVID-19 are advised to use respirators at least as protective as NIOSH-certified N95 or equivalent, in addition to other personal protective equipment.
HAND-WASHING AND HYGIENE
Thorough hand hygiene after any cough or sneeze is required. The WHO also recommends that individuals wash hands often with soap and water for at least 20 seconds, especially after going to the toilet or when hands are visibly dirty, before eating and after blowing one's nose. The CDC recommends using an alcohol-based hand sanitiser with at least 60% alcohol, but only when soap and water are not readily available. For areas where commercial hand sanitisers are not readily available, the WHO provides two formulations for local production. In these formulations, the antimicrobial activity arises from ethanol or isopropanol. Hydrogen peroxide is used to help eliminate bacterial spores in the alcohol; it is "not an active substance for hand antisepsis". Glycerol is added as a humectant.
SURFACE CLEANING
After being expelled from the body, coronaviruses can survive on surfaces for hours to days. If a person touches the dirty surface, they may deposit the virus at the eyes, nose, or mouth where it can enter the body cause infection. Current evidence indicates that contact with infected surfaces is not the main driver of Covid-19, leading to recommendations for optimised disinfection procedures to avoid issues such as the increase of antimicrobial resistance through the use of inappropriate cleaning products and processes. Deep cleaning and other surface sanitation has been criticized as hygiene theater, giving a false sense of security against something primarily spread through the air.
The amount of time that the virus can survive depends significantly on the type of surface, the temperature, and the humidity. Coronaviruses die very quickly when exposed to the UV light in sunlight. Like other enveloped viruses, SARS-CoV-2 survives longest when the temperature is at room temperature or lower, and when the relative humidity is low (<50%).
On many surfaces, including as glass, some types of plastic, stainless steel, and skin, the virus can remain infective for several days indoors at room temperature, or even about a week under ideal conditions. On some surfaces, including cotton fabric and copper, the virus usually dies after a few hours. As a general rule of thumb, the virus dies faster on porous surfaces than on non-porous surfaces.
However, this rule is not absolute, and of the many surfaces tested, two with the longest survival times are N95 respirator masks and surgical masks, both of which are considered porous surfaces.
Surfaces may be decontaminated with 62–71 percent ethanol, 50–100 percent isopropanol, 0.1 percent sodium hypochlorite, 0.5 percent hydrogen peroxide, and 0.2–7.5 percent povidone-iodine. Other solutions, such as benzalkonium chloride and chlorhexidine gluconate, are less effective. Ultraviolet germicidal irradiation may also be used. The CDC recommends that if a COVID-19 case is suspected or confirmed at a facility such as an office or day care, all areas such as offices, bathrooms, common areas, shared electronic equipment like tablets, touch screens, keyboards, remote controls, and ATM machines used by the ill persons should be disinfected. A datasheet comprising the authorised substances to disinfection in the food industry (including suspension or surface tested, kind of surface, use dilution, disinfectant and inocuylum volumes) can be seen in the supplementary material of.
VENTILATION AND AIR FILTRATION
The WHO recommends ventilation and air filtration in public spaces to help clear out infectious aerosols.
HEALTHY DIET AND LIFESTYLE
The Harvard T.H. Chan School of Public Health recommends a healthy diet, being physically active, managing psychological stress, and getting enough sleep.
While there is no evidence that vitamin D is an effective treatment for COVID-19, there is limited evidence that vitamin D deficiency increases the risk of severe COVID-19 symptoms. This has led to recommendations for individuals with vitamin D deficiency to take vitamin D supplements as a way of mitigating the risk of COVID-19 and other health issues associated with a possible increase in deficiency due to social distancing.
TREATMENT
There is no specific, effective treatment or cure for coronavirus disease 2019 (COVID-19), the disease caused by the SARS-CoV-2 virus. Thus, the cornerstone of management of COVID-19 is supportive care, which includes treatment to relieve symptoms, fluid therapy, oxygen support and prone positioning as needed, and medications or devices to support other affected vital organs.
Most cases of COVID-19 are mild. In these, supportive care includes medication such as paracetamol or NSAIDs to relieve symptoms (fever, body aches, cough), proper intake of fluids, rest, and nasal breathing. Good personal hygiene and a healthy diet are also recommended. The U.S. Centers for Disease Control and Prevention (CDC) recommend that those who suspect they are carrying the virus isolate themselves at home and wear a face mask.
People with more severe cases may need treatment in hospital. In those with low oxygen levels, use of the glucocorticoid dexamethasone is strongly recommended, as it can reduce the risk of death. Noninvasive ventilation and, ultimately, admission to an intensive care unit for mechanical ventilation may be required to support breathing. Extracorporeal membrane oxygenation (ECMO) has been used to address the issue of respiratory failure, but its benefits are still under consideration.
Several experimental treatments are being actively studied in clinical trials. Others were thought to be promising early in the pandemic, such as hydroxychloroquine and lopinavir/ritonavir, but later research found them to be ineffective or even harmful. Despite ongoing research, there is still not enough high-quality evidence to recommend so-called early treatment. Nevertheless, in the United States, two monoclonal antibody-based therapies are available for early use in cases thought to be at high risk of progression to severe disease. The antiviral remdesivir is available in the U.S., Canada, Australia, and several other countries, with varying restrictions; however, it is not recommended for people needing mechanical ventilation, and is discouraged altogether by the World Health Organization (WHO), due to limited evidence of its efficacy.
PROGNOSIS
The severity of COVID-19 varies. The disease may take a mild course with few or no symptoms, resembling other common upper respiratory diseases such as the common cold. In 3–4% of cases (7.4% for those over age 65) symptoms are severe enough to cause hospitalization. Mild cases typically recover within two weeks, while those with severe or critical diseases may take three to six weeks to recover. Among those who have died, the time from symptom onset to death has ranged from two to eight weeks. The Italian Istituto Superiore di Sanità reported that the median time between the onset of symptoms and death was twelve days, with seven being hospitalised. However, people transferred to an ICU had a median time of ten days between hospitalisation and death. Prolonged prothrombin time and elevated C-reactive protein levels on admission to the hospital are associated with severe course of COVID-19 and with a transfer to ICU.
Some early studies suggest 10% to 20% of people with COVID-19 will experience symptoms lasting longer than a month.[191][192] A majority of those who were admitted to hospital with severe disease report long-term problems including fatigue and shortness of breath. On 30 October 2020 WHO chief Tedros Adhanom warned that "to a significant number of people, the COVID virus poses a range of serious long-term effects". He has described the vast spectrum of COVID-19 symptoms that fluctuate over time as "really concerning." They range from fatigue, a cough and shortness of breath, to inflammation and injury of major organs – including the lungs and heart, and also neurological and psychologic effects. Symptoms often overlap and can affect any system in the body. Infected people have reported cyclical bouts of fatigue, headaches, months of complete exhaustion, mood swings, and other symptoms. Tedros has concluded that therefore herd immunity is "morally unconscionable and unfeasible".
In terms of hospital readmissions about 9% of 106,000 individuals had to return for hospital treatment within 2 months of discharge. The average to readmit was 8 days since first hospital visit. There are several risk factors that have been identified as being a cause of multiple admissions to a hospital facility. Among these are advanced age (above 65 years of age) and presence of a chronic condition such as diabetes, COPD, heart failure or chronic kidney disease.
According to scientific reviews smokers are more likely to require intensive care or die compared to non-smokers, air pollution is similarly associated with risk factors, and pre-existing heart and lung diseases and also obesity contributes to an increased health risk of COVID-19.
It is also assumed that those that are immunocompromised are at higher risk of getting severely sick from SARS-CoV-2. One research that looked into the COVID-19 infections in hospitalized kidney transplant recipients found a mortality rate of 11%.
See also: Impact of the COVID-19 pandemic on children
Children make up a small proportion of reported cases, with about 1% of cases being under 10 years and 4% aged 10–19 years. They are likely to have milder symptoms and a lower chance of severe disease than adults. A European multinational study of hospitalized children published in The Lancet on 25 June 2020 found that about 8% of children admitted to a hospital needed intensive care. Four of those 582 children (0.7%) died, but the actual mortality rate could be "substantially lower" since milder cases that did not seek medical help were not included in the study.
Genetics also plays an important role in the ability to fight off the disease. For instance, those that do not produce detectable type I interferons or produce auto-antibodies against these may get much sicker from COVID-19. Genetic screening is able to detect interferon effector genes.
Pregnant women may be at higher risk of severe COVID-19 infection based on data from other similar viruses, like SARS and MERS, but data for COVID-19 is lacking.
COMPLICATIONS
Complications may include pneumonia, acute respiratory distress syndrome (ARDS), multi-organ failure, septic shock, and death. Cardiovascular complications may include heart failure, arrhythmias, heart inflammation, and blood clots. Approximately 20–30% of people who present with COVID-19 have elevated liver enzymes, reflecting liver injury.
Neurologic manifestations include seizure, stroke, encephalitis, and Guillain–Barré syndrome (which includes loss of motor functions). Following the infection, children may develop paediatric multisystem inflammatory syndrome, which has symptoms similar to Kawasaki disease, which can be fatal. In very rare cases, acute encephalopathy can occur, and it can be considered in those who have been diagnosed with COVID-19 and have an altered mental status.
LONGER-TERM EFFECTS
Some early studies suggest that that 10 to 20% of people with COVID-19 will experience symptoms lasting longer than a month. A majority of those who were admitted to hospital with severe disease report long-term problems, including fatigue and shortness of breath. About 5-10% of patients admitted to hospital progress to severe or critical disease, including pneumonia and acute respiratory failure.
By a variety of mechanisms, the lungs are the organs most affected in COVID-19.[228] The majority of CT scans performed show lung abnormalities in people tested after 28 days of illness.
People with advanced age, severe disease, prolonged ICU stays, or who smoke are more likely to have long lasting effects, including pulmonary fibrosis. Overall, approximately one third of those investigated after 4 weeks will have findings of pulmonary fibrosis or reduced lung function as measured by DLCO, even in people who are asymptomatic, but with the suggestion of continuing improvement with the passing of more time.
IMMUNITY
The immune response by humans to CoV-2 virus occurs as a combination of the cell-mediated immunity and antibody production, just as with most other infections. Since SARS-CoV-2 has been in the human population only since December 2019, it remains unknown if the immunity is long-lasting in people who recover from the disease. The presence of neutralizing antibodies in blood strongly correlates with protection from infection, but the level of neutralizing antibody declines with time. Those with asymptomatic or mild disease had undetectable levels of neutralizing antibody two months after infection. In another study, the level of neutralizing antibody fell 4-fold 1 to 4 months after the onset of symptoms. However, the lack of antibody in the blood does not mean antibody will not be rapidly produced upon reexposure to SARS-CoV-2. Memory B cells specific for the spike and nucleocapsid proteins of SARS-CoV-2 last for at least 6 months after appearance of symptoms. Nevertheless, 15 cases of reinfection with SARS-CoV-2 have been reported using stringent CDC criteria requiring identification of a different variant from the second infection. There are likely to be many more people who have been reinfected with the virus. Herd immunity will not eliminate the virus if reinfection is common. Some other coronaviruses circulating in people are capable of reinfection after roughly a year. Nonetheless, on 3 March 2021, scientists reported that a much more contagious Covid-19 variant, Lineage P.1, first detected in Japan, and subsequently found in Brazil, as well as in several places in the United States, may be associated with Covid-19 disease reinfection after recovery from an earlier Covid-19 infection.
MORTALITY
Several measures are commonly used to quantify mortality. These numbers vary by region and over time and are influenced by the volume of testing, healthcare system quality, treatment options, time since the initial outbreak, and population characteristics such as age, sex, and overall health. The mortality rate reflects the number of deaths within a specific demographic group divided by the population of that demographic group. Consequently, the mortality rate reflects the prevalence as well as the severity of the disease within a given population. Mortality rates are highly correlated to age, with relatively low rates for young people and relatively high rates among the elderly.
The case fatality rate (CFR) reflects the number of deaths divided by the number of diagnosed cases within a given time interval. Based on Johns Hopkins University statistics, the global death-to-case ratio is 2.2% (2,685,770/121,585,388) as of 18 March 2021. The number varies by region. The CFR may not reflect the true severity of the disease, because some infected individuals remain asymptomatic or experience only mild symptoms, and hence such infections may not be included in official case reports. Moreover, the CFR may vary markedly over time and across locations due to the availability of live virus tests.
INFECTION FATALITY RATE
A key metric in gauging the severity of COVID-19 is the infection fatality rate (IFR), also referred to as the infection fatality ratio or infection fatality risk. This metric is calculated by dividing the total number of deaths from the disease by the total number of infected individuals; hence, in contrast to the CFR, the IFR incorporates asymptomatic and undiagnosed infections as well as reported cases.
CURRENT ESTIMATES
A December 2020 systematic review and meta-analysis estimated that population IFR during the first wave of the pandemic was about 0.5% to 1% in many locations (including France, Netherlands, New Zealand, and Portugal), 1% to 2% in other locations (Australia, England, Lithuania, and Spain), and exceeded 2% in Italy. That study also found that most of these differences in IFR reflected corresponding differences in the age composition of the population and age-specific infection rates; in particular, the metaregression estimate of IFR is very low for children and younger adults (e.g., 0.002% at age 10 and 0.01% at age 25) but increases progressively to 0.4% at age 55, 1.4% at age 65, 4.6% at age 75, and 15% at age 85. These results were also highlighted in a December 2020 report issued by the WHO.
EARLIER ESTIMATES OF IFR
At an early stage of the pandemic, the World Health Organization reported estimates of IFR between 0.3% and 1%.[ On 2 July, The WHO's chief scientist reported that the average IFR estimate presented at a two-day WHO expert forum was about 0.6%. In August, the WHO found that studies incorporating data from broad serology testing in Europe showed IFR estimates converging at approximately 0.5–1%. Firm lower limits of IFRs have been established in a number of locations such as New York City and Bergamo in Italy since the IFR cannot be less than the population fatality rate. As of 10 July, in New York City, with a population of 8.4 million, 23,377 individuals (18,758 confirmed and 4,619 probable) have died with COVID-19 (0.3% of the population).Antibody testing in New York City suggested an IFR of ~0.9%,[258] and ~1.4%. In Bergamo province, 0.6% of the population has died. In September 2020 the U.S. Center for Disease Control & Prevention reported preliminary estimates of age-specific IFRs for public health planning purposes.
SEX DIFFERENCES
Early reviews of epidemiologic data showed gendered impact of the pandemic and a higher mortality rate in men in China and Italy. The Chinese Center for Disease Control and Prevention reported the death rate was 2.8% for men and 1.7% for women. Later reviews in June 2020 indicated that there is no significant difference in susceptibility or in CFR between genders. One review acknowledges the different mortality rates in Chinese men, suggesting that it may be attributable to lifestyle choices such as smoking and drinking alcohol rather than genetic factors. Sex-based immunological differences, lesser prevalence of smoking in women and men developing co-morbid conditions such as hypertension at a younger age than women could have contributed to the higher mortality in men. In Europe, 57% of the infected people were men and 72% of those died with COVID-19 were men. As of April 2020, the US government is not tracking sex-related data of COVID-19 infections. Research has shown that viral illnesses like Ebola, HIV, influenza and SARS affect men and women differently.
ETHNIC DIFFERENCES
In the US, a greater proportion of deaths due to COVID-19 have occurred among African Americans and other minority groups. Structural factors that prevent them from practicing social distancing include their concentration in crowded substandard housing and in "essential" occupations such as retail grocery workers, public transit employees, health-care workers and custodial staff. Greater prevalence of lacking health insurance and care and of underlying conditions such as diabetes, hypertension and heart disease also increase their risk of death. Similar issues affect Native American and Latino communities. According to a US health policy non-profit, 34% of American Indian and Alaska Native People (AIAN) non-elderly adults are at risk of serious illness compared to 21% of white non-elderly adults. The source attributes it to disproportionately high rates of many health conditions that may put them at higher risk as well as living conditions like lack of access to clean water. Leaders have called for efforts to research and address the disparities. In the U.K., a greater proportion of deaths due to COVID-19 have occurred in those of a Black, Asian, and other ethnic minority background. More severe impacts upon victims including the relative incidence of the necessity of hospitalization requirements, and vulnerability to the disease has been associated via DNA analysis to be expressed in genetic variants at chromosomal region 3, features that are associated with European Neanderthal heritage. That structure imposes greater risks that those affected will develop a more severe form of the disease. The findings are from Professor Svante Pääbo and researchers he leads at the Max Planck Institute for Evolutionary Anthropology and the Karolinska Institutet. This admixture of modern human and Neanderthal genes is estimated to have occurred roughly between 50,000 and 60,000 years ago in Southern Europe.
COMORBIDITIES
Most of those who die of COVID-19 have pre-existing (underlying) conditions, including hypertension, diabetes mellitus, and cardiovascular disease. According to March data from the United States, 89% of those hospitalised had preexisting conditions. The Italian Istituto Superiore di Sanità reported that out of 8.8% of deaths where medical charts were available, 96.1% of people had at least one comorbidity with the average person having 3.4 diseases. According to this report the most common comorbidities are hypertension (66% of deaths), type 2 diabetes (29.8% of deaths), Ischemic Heart Disease (27.6% of deaths), atrial fibrillation (23.1% of deaths) and chronic renal failure (20.2% of deaths).
Most critical respiratory comorbidities according to the CDC, are: moderate or severe asthma, pre-existing COPD, pulmonary fibrosis, cystic fibrosis. Evidence stemming from meta-analysis of several smaller research papers also suggests that smoking can be associated with worse outcomes. When someone with existing respiratory problems is infected with COVID-19, they might be at greater risk for severe symptoms. COVID-19 also poses a greater risk to people who misuse opioids and methamphetamines, insofar as their drug use may have caused lung damage.
In August 2020 the CDC issued a caution that tuberculosis infections could increase the risk of severe illness or death. The WHO recommended that people with respiratory symptoms be screened for both diseases, as testing positive for COVID-19 couldn't rule out co-infections. Some projections have estimated that reduced TB detection due to the pandemic could result in 6.3 million additional TB cases and 1.4 million TB related deaths by 2025.
NAME
During the initial outbreak in Wuhan, China, the virus and disease were commonly referred to as "coronavirus" and "Wuhan coronavirus", with the disease sometimes called "Wuhan pneumonia". In the past, many diseases have been named after geographical locations, such as the Spanish flu, Middle East Respiratory Syndrome, and Zika virus. In January 2020, the WHO recommended 2019-nCov and 2019-nCoV acute respiratory disease as interim names for the virus and disease per 2015 guidance and international guidelines against using geographical locations (e.g. Wuhan, China), animal species, or groups of people in disease and virus names in part to prevent social stigma. The official names COVID-19 and SARS-CoV-2 were issued by the WHO on 11 February 2020. Tedros Adhanom explained: CO for corona, VI for virus, D for disease and 19 for when the outbreak was first identified (31 December 2019). The WHO additionally uses "the COVID-19 virus" and "the virus responsible for COVID-19" in public communications.
HISTORY
The virus is thought to be natural and of an animal origin, through spillover infection. There are several theories about where the first case (the so-called patient zero) originated. Phylogenetics estimates that SARS-CoV-2 arose in October or November 2019. Evidence suggests that it descends from a coronavirus that infects wild bats, and spread to humans through an intermediary wildlife host.
The first known human infections were in Wuhan, Hubei, China. A study of the first 41 cases of confirmed COVID-19, published in January 2020 in The Lancet, reported the earliest date of onset of symptoms as 1 December 2019.Official publications from the WHO reported the earliest onset of symptoms as 8 December 2019. Human-to-human transmission was confirmed by the WHO and Chinese authorities by 20 January 2020. According to official Chinese sources, these were mostly linked to the Huanan Seafood Wholesale Market, which also sold live animals. In May 2020 George Gao, the director of the CDC, said animal samples collected from the seafood market had tested negative for the virus, indicating that the market was the site of an early superspreading event, but that it was not the site of the initial outbreak.[ Traces of the virus have been found in wastewater samples that were collected in Milan and Turin, Italy, on 18 December 2019.
By December 2019, the spread of infection was almost entirely driven by human-to-human transmission. The number of coronavirus cases in Hubei gradually increased, reaching 60 by 20 December, and at least 266 by 31 December. On 24 December, Wuhan Central Hospital sent a bronchoalveolar lavage fluid (BAL) sample from an unresolved clinical case to sequencing company Vision Medicals. On 27 and 28 December, Vision Medicals informed the Wuhan Central Hospital and the Chinese CDC of the results of the test, showing a new coronavirus. A pneumonia cluster of unknown cause was observed on 26 December and treated by the doctor Zhang Jixian in Hubei Provincial Hospital, who informed the Wuhan Jianghan CDC on 27 December. On 30 December, a test report addressed to Wuhan Central Hospital, from company CapitalBio Medlab, stated an erroneous positive result for SARS, causing a group of doctors at Wuhan Central Hospital to alert their colleagues and relevant hospital authorities of the result. The Wuhan Municipal Health Commission issued a notice to various medical institutions on "the treatment of pneumonia of unknown cause" that same evening. Eight of these doctors, including Li Wenliang (punished on 3 January), were later admonished by the police for spreading false rumours and another, Ai Fen, was reprimanded by her superiors for raising the alarm.
The Wuhan Municipal Health Commission made the first public announcement of a pneumonia outbreak of unknown cause on 31 December, confirming 27 cases—enough to trigger an investigation.
During the early stages of the outbreak, the number of cases doubled approximately every seven and a half days. In early and mid-January 2020, the virus spread to other Chinese provinces, helped by the Chinese New Year migration and Wuhan being a transport hub and major rail interchange. On 20 January, China reported nearly 140 new cases in one day, including two people in Beijing and one in Shenzhen. Later official data shows 6,174 people had already developed symptoms by then, and more may have been infected. A report in The Lancet on 24 January indicated human transmission, strongly recommended personal protective equipment for health workers, and said testing for the virus was essential due to its "pandemic potential". On 30 January, the WHO declared the coronavirus a Public Health Emergency of International Concern. By this time, the outbreak spread by a factor of 100 to 200 times.
Italy had its first confirmed cases on 31 January 2020, two tourists from China. As of 13 March 2020 the WHO considered Europe the active centre of the pandemic. Italy overtook China as the country with the most deaths on 19 March 2020. By 26 March the United States had overtaken China and Italy with the highest number of confirmed cases in the world. Research on coronavirus genomes indicates the majority of COVID-19 cases in New York came from European travellers, rather than directly from China or any other Asian country. Retesting of prior samples found a person in France who had the virus on 27 December 2019, and a person in the United States who died from the disease on 6 February 2020.
After 55 days without a locally transmitted case, Beijing reported a new COVID-19 case on 11 June 2020 which was followed by two more cases on 12 June. By 15 June there were 79 cases officially confirmed, most of them were people that went to Xinfadi Wholesale Market.
RT-PCR testing of untreated wastewater samples from Brazil and Italy have suggested detection of SARS-CoV-2 as early as November and December 2019, respectively, but the methods of such sewage studies have not been optimised, many have not been peer reviewed, details are often missing, and there is a risk of false positives due to contamination or if only one gene target is detected. A September 2020 review journal article said, "The possibility that the COVID-19 infection had already spread to Europe at the end of last year is now indicated by abundant, even if partially circumstantial, evidence", including pneumonia case numbers and radiology in France and Italy in November and December.
MISINFORMATION
After the initial outbreak of COVID-19, misinformation and disinformation regarding the origin, scale, prevention, treatment, and other aspects of the disease rapidly spread online.
In September 2020, the U.S. CDC published preliminary estimates of the risk of death by age groups in the United States, but those estimates were widely misreported and misunderstood.
OTHER ANIMALS
Humans appear to be capable of spreading the virus to some other animals, a type of disease transmission referred to as zooanthroponosis.
Some pets, especially cats and ferrets, can catch this virus from infected humans. Symptoms in cats include respiratory (such as a cough) and digestive symptoms. Cats can spread the virus to other cats, and may be able to spread the virus to humans, but cat-to-human transmission of SARS-CoV-2 has not been proven. Compared to cats, dogs are less susceptible to this infection. Behaviors which increase the risk of transmission include kissing, licking, and petting the animal.
The virus does not appear to be able to infect pigs, ducks, or chickens at all.[ Mice, rats, and rabbits, if they can be infected at all, are unlikely to be involved in spreading the virus.
Tigers and lions in zoos have become infected as a result of contact with infected humans. As expected, monkeys and great ape species such as orangutans can also be infected with the COVID-19 virus.
Minks, which are in the same family as ferrets, have been infected. Minks may be asymptomatic, and can also spread the virus to humans. Multiple countries have identified infected animals in mink farms. Denmark, a major producer of mink pelts, ordered the slaughter of all minks over fears of viral mutations. A vaccine for mink and other animals is being researched.
RESEARCH
International research on vaccines and medicines in COVID-19 is underway by government organisations, academic groups, and industry researchers. The CDC has classified it to require a BSL3 grade laboratory. There has been a great deal of COVID-19 research, involving accelerated research processes and publishing shortcuts to meet the global demand.
As of December 2020, hundreds of clinical trials have been undertaken, with research happening on every continent except Antarctica. As of November 2020, more than 200 possible treatments had been studied in humans so far.
Transmission and prevention research
Modelling research has been conducted with several objectives, including predictions of the dynamics of transmission, diagnosis and prognosis of infection, estimation of the impact of interventions, or allocation of resources. Modelling studies are mostly based on epidemiological models, estimating the number of infected people over time under given conditions. Several other types of models have been developed and used during the COVID-19 including computational fluid dynamics models to study the flow physics of COVID-19, retrofits of crowd movement models to study occupant exposure, mobility-data based models to investigate transmission, or the use of macroeconomic models to assess the economic impact of the pandemic. Further, conceptual frameworks from crisis management research have been applied to better understand the effects of COVID-19 on organizations worldwide.
TREATMENT-RELATED RESEARCH
Repurposed antiviral drugs make up most of the research into COVID-19 treatments. Other candidates in trials include vasodilators, corticosteroids, immune therapies, lipoic acid, bevacizumab, and recombinant angiotensin-converting enzyme 2.
In March 2020, the World Health Organization (WHO) initiated the Solidarity trial to assess the treatment effects of some promising drugs: an experimental drug called remdesivir; anti-malarial drugs chloroquine and hydroxychloroquine; two anti-HIV drugs, lopinavir/ritonavir; and interferon-beta. More than 300 active clinical trials were underway as of April 2020.
Research on the antimalarial drugs hydroxychloroquine and chloroquine showed that they were ineffective at best, and that they may reduce the antiviral activity of remdesivir. By May 2020, France, Italy, and Belgium had banned the use of hydroxychloroquine as a COVID-19 treatment.
In June, initial results from the randomised RECOVERY Trial in the United Kingdom showed that dexamethasone reduced mortality by one third for people who are critically ill on ventilators and one fifth for those receiving supplemental oxygen. Because this is a well-tested and widely available treatment, it was welcomed by the WHO, which is in the process of updating treatment guidelines to include dexamethasone and other steroids. Based on those preliminary results, dexamethasone treatment has been recommended by the NIH for patients with COVID-19 who are mechanically ventilated or who require supplemental oxygen but not in patients with COVID-19 who do not require supplemental oxygen.
In September 2020, the WHO released updated guidance on using corticosteroids for COVID-19. The WHO recommends systemic corticosteroids rather than no systemic corticosteroids for the treatment of people with severe and critical COVID-19 (strong recommendation, based on moderate certainty evidence). The WHO suggests not to use corticosteroids in the treatment of people with non-severe COVID-19 (conditional recommendation, based on low certainty evidence). The updated guidance was based on a meta-analysis of clinical trials of critically ill COVID-19 patients.
WIKIPEDIA