Depuis quelques temps je me retrouve sur le devant de la scène , je n'ai rien demandé à personne. Certains mandarins m'adulent , les autres me haïssent. J'aimerais pouvoir sauver le monde mais en suis je capable? Bon, je crois que je vais rejoindre mon placard en attendant leur décison, mais à mon avis 4euros je ne suis pas assez rentable, je ne vais pas pouvoir rivaliser. Tant pis j'aurais eu mon moment de gloire!!!!!!!

Lady Cardinal in our backyard.

Do not be in the dark ages with the information on the COVID19, The more you know the more bulletproof you are! Dr. Fauci did a study in 2005 on how good hydroxychloroquine worked with viruses, the French version of Dr. Fauci, Dr. Didier Raoult began working with patients using the HCQ adding the Z pack antibiotics and later a dose of Zinc. The combination of all three was working wonders with those caught with first symptons, working great with elderly, and even saving elderly with those conditions that were the death sentence earlier. So if you feel you may have this sickness do as the Democrat state Rep. Karen Whitsett of Detroit who had this in the progressive stages and ask your doctor for this combination. I also believe many will be surprised at how MANY viruses this will kill or make dormant. There is so much more to learn if you dig into the research, France, Italy, Russia, China and USA are all using this very cheap and effective medicine combo, but the push is for the most expensive therapeutics and the wait for a vaccine that will not be as effective. Do what you want with a mask but be sure if you do wear it keep it clean, bacteria from your mouth finds this a breeding ground, as with any sickness being CLEAN is KEY.

 

docs.google.com/document/d/1545C_dJWMIAgqeLEsfo2U8Kq5WprD...

The quote is really from a recent press conference related to suggesting citizens experiment with an anti-malaria drug (hydroxychloroquine) as treatment for the Covid-19 virus.

 

Newport, Rhode Island

 

A view of the northern end of Goat Island in Narragansett Bay, occupied by Gurney’s Newport Resort & Marina and the adjacent Newport Harbor Light. This small island is connected to Newport proper via a causeway bridge, visible behind the dock in the upper left, from where this picture of the Newport Bridge was taken a while back. The island also has quite a bit of naval history going back before the Revolutionary War.

 

No, the seaweed isn't actually that color. I took some artistic liberty with the "Indian Summer" filter in Nik Collection's Color Efex Pro because I thought it looked cool, and reality isn't all it's cracked up to be. After wall, what did I have to lose? ;-)

 

Lens: 24mm tilt-shift, shifted down about halfway

Filters: landscape polarizer, 2-stop soft-edge GND, 10-stop ND

Hydroxychloroquine induced madness has set in.

I've done another run of new and old ag. stuff and find I have not recently added a shot from Golden Ponds. Considering the onslaught of the Trump Neo-Stormers at the Longmont parks, walks are dangerous here until the herd learns something of reality... and immunity. Give 'em at least a couple of weeks and down some bleach. I found an unedit while in the days of Don Corona Trumpandemic and will stay somewhat safe at home for today and the next two weeks when the WH Trumpandemic should really flower while Darwin hides in waiting especially for Floridians and Texicans who don't even report virus cases and deaths. Then we can re-erect the southern border wall in the proper location and boy will those taker states loose their federal payloads, and do they ever cost the rest of the states a load. It's probably also up to us to bury their dead.

 

Nevertheless, I found this late-day oddity from an earlier spring, something recently lost to the valley. The sunbeam seems to be shining down on the St. Malo Camp and St. Catherine's Chapel at the bottom of Mount Meeker. There is probably no one throwing meteorites around Meeker for catholics to find like the 2800 BC Birkle comet strike in the Indian Ocean, causing all kinds of flood stories. It's probably also up to us to bury their dead.

 

I don't have the access to WH testing (48% accurate) that the WH seems to have found among the US health desert and they maintain the testing for themselves only. A dip in this pond looks even shakier than a dip in the WH swampage waiting for herd immunity (herd stupidity?). Well, we can all pull for the hydroxychloroquine to do the job as the VET described (increased deaths) - just one more in the string of lies in the first place.

 

After a walk at Golden Ponds on that day, I am finally glad for today's neo-greenup in the valley and an escape from the the Trumpendemic-19 dead and dying with this shot and a shooter of bleach. Ahhh, a day in the park... and strange lighting that really jumps from the frame. It beats any stay-at-home-day in the valley.

 

I wandered the green space and took interest in shots that were available, I mostly enjoyed including thjs strange sky.

  

Wade out there to grab that snag! No way; you go out and grab it! I'm not walking into that pond! There's always detritus falling into the Golden Ponds. Maybe you will hook it then retrieve it while fishing. I've walked into Rocky waters like this before, especially to fly fish in mountain streams, but I guess that I will let it go in the days of Don Corona Trumpandemic and stay somewhat clean at least today and the next two weeks when the WH Trumpandemic should really flower while Darwin hides in waiting especially for Floridians and Texicans. Then we can re-erect the southern border wall in the proper location and boy will those taker states loose their payloads. However, I fear that if I get wet, my shirt will trigger a mud slide. I don't have the access to WH testing (though only 48% accurate) that the WH seems to have found among the US desert and they maintain the testing for themselves only. A dip in this pond looks even shakier than a dip in the WH swampage waiting for herd immunity (herd stupidity?). Well, we can all pull for the hydroxychloroquine to do the job as the VET described (increased deaths) - assuming that wasn't just one more in the string of lies in the first place.

 

After a walk at Golden Ponds on that day, I am finally glad for today's neo-greenup in the valley and an escape from the the Trumpendemic-19 dead and dying with this shot and a shooter of bleach. Ahhh, an autumn day in the park... and lighting that really jumps from the frame. It beats any stay-at-home-day in the valley. And to think that Ethiopia in regreening the desert themselves without help from Agent Orange and set the one day tree-planting record at 350 million trees planted in 12 hours. Apparently there are countries with people taking back all their own rights and lives. Is it still possible in this country? Even with corporate Dems in the way of progress?

 

The best vid of future hope on the net: www.youtube.com/watch?v=IDgDWbQtlKI

 

I had no skies warranting a background. I wandered the green space and took interest in shots that were available, I mostly avoided including the crummy sky.

  

Causes of gradual vision loss

 

1.Painless loss

 

Refractive error - this is characterised by an improvement of the visual acuity with the use of a pinhole (if you don't have a specific occluder with pinholes, a biro point-sized hole in a stiff piece of cardboard will do). Refer to the optician.

 

Cataracts - the patient often complains of glare in dark conditions (and so difficulty in driving at night) and may complain that colours appear more dull than they used to. There may be an abnormal red reflex and, in advanced cases, the cataract may be visible to the naked eye (this is increasingly rare these days). Other aspects of the examination should be normal unless there is concurrent pathology. Refer routinely.

 

Age-related macular degeneration (AMD) - suspect AMD if the patient is aged >50 years and is presenting with either of the following symptoms, usually affecting one eye at a time:

Distortion of vision, where straight lines appear crooked or wavy.

Painless loss or blurring of central or near-central vision. The person may describe a black or grey patch affecting their central field of vision (scotoma).

 

Various other visual symptoms can occur, or AMD may be an incidental finding by an optometrist. Visual acuity on a Snellen chart may be normal or reduced. When viewing an Amsler chart (or graph paper), patients may see breaks, waviness, or missing portions of the lines. Refer urgently if AMD is suspected.

 

Chronic (primary) open-angle glaucoma - is most commonly picked up through screening. If it is so advanced that the patient is the first to notice it, very little can be done. It is characterised by a progressive peripheral visual field loss and 'cupping' of the optic discs (the central area of the optic disc enlarges and the peripheral rim thins out). The degree of urgency depends on how advanced the damage is.

 

Diabetic retinopathy - the problem may be due to the diabetic microvascular problems (ie exudates and haemorrhages), to associated pathology (eg, diabetic cataract) or unrelated pathology (eg, glaucoma). Refer promptly (within a week), as prompt treatment may prevent deterioration.

 

Compression of optic nerve or optic pathway - rare, but should be considered if there is a history of headaches and if you find any neurological or endocrinological abnormalities (eg, acromegaly) on examination. Look for a relative afferent pupillary defect (not usually present in the above conditions), a pale or swollen optic disc (the margins are not clear) and visual field defects.

 

Drugs, toxins or nutritional deficiency - eg:

Amiodarone - various effects on the eye

Antituberculous drugs - ethambutol and isoniazid (optic neuritis).

Hydroxychloroquine (maculopathy).

Systemic steroids (cataracts and glaucoma)

Phosphodiesterase inhibitors (eg, sildenafil).

 

Others drugs - tetracyclines (benign intracranial hypertension), isotretinoin, tamoxifen (various possible effects on vision).

Alcohol, smoking and nutritional deficiency - eg:

Tobacco-alcohol amblyopia.

Methanol poisoning.

 

Vitamin A deficiency (classically causes night blindness).

 

Hereditary retinal dystrophies are rare and, depending on the exact problem, present anywhere from early childhood to middle age. Some are rapidly progressing; others are very slow. Typical features particularly include poor night vision and intolerance to light. Poor appreciation of movement in the peripheral visual field may also be a feature. Ask about similar problems in family members (who may not have been diagnosed). Children should be referred more promptly than adults for whom a routine referral is fine. These patients will need genetic counselling as well as support where the prognosis is poor.

 

Cerebrovascular disease (stroke and TIA) - although these are likely to present acutely. TIA causing visual loss is termed amaurosis fugax.

Papilloedema - eg, from intracranial hypertension.

 

-----------------------

 

2. Painful loss

 

This is much rarer and tends to suggest a more sinister pathology such as:

A progressive neoplastic (eg, choroidal melanoma) or inflammatory process (eg, chorioretinitis).

A systemic problem (eg, sarcoidosis or collagen vascular disease).

Lesions on the optic nerve (eg, optic neuritis, granuloma or neuroma).

Intracranial pathology or masses (may present with headache, or with endocrine symptoms if a pituitary tumour).

Intracranial hypertension (may have headache).

 

All these patients should be referred. Referral is more urgent than with painless conditions and patients should really be seen within a few days.

  

If there is a problem, don't wait seek medical help.

 

---------------

Candid street shot Bergen, Norway.

At a gas station in sassy, vivacious San Bruno, California...

July 2020

Watching Donald Trump’s pandemic briefings is insufferable. The President is often argumentative and dispenses information that is superfluous and often dangerous. During his March 19 briefing, he first promoted the antimalarial drug hydroxychlorquine as a potential cure for COVID-19. By the next week, over 101,000 posts about the drug had appeared on Facebook, and by late March, there were hundreds of thousands of tweets about it per hour. Donald Trump is effective when using his bully pulpit.

 

There is no scientific evidence that hydroxychlorquine, a medication used by those with lupus and rheumatoid arthritis, is effective against the coronavirus. In fact, scientists in Brazil cut short a trial when it showed this drug and its close relative, chloroquine, could adversely affect the heart. Hospitals in Sweden and American cardiology groups cautioned doctors these drugs could be harmful to those with existing heart problems.

 

Despite those warnings, in his April 4 briefing, the President was cavalier when he said, “What do you have to lose? I’ll say it again: What do you have to lose? Take it. I really think they should take it.” An Arizona man, heeding Trump’s advice, died when he ingested chloroquine phosphate, a drug that sounds like chloroquine, but is used to clean fish tanks. Lives are lost when people take the advice of someone with no medical background, including the President of the United States.

 

At his April 23 briefing, the President came up with another cure: injecting ourselves with disinfectants. These are effective in destroying COVID-19 on surfaces and countertops. But taken internally, they are toxic. His suggestion stunned the scientific community. Given the weight of his office, doctors and the makers of Lysol and Clorox warned the public against consuming bleach and other cleaning agents. The Maryland Emergency Management Agency received over 100 calls about this in the hours and days after Trump’s statement. Even more alarming, the New York Daily News reported the city’s Poison Control Center fielded over 30 calls the day after Trump’s comments from people who had taken Lysol, bleach, or other household cleaners.

 

The outcry was so great, Trump walked back his recommendations the next day: “I was asking a question sarcastically to reporters like you just to see what would happen.” For the record, he offered his remedy with no prompting by reporters. But, what can one expect from a man who believes he has an innate understanding of medical science. The President has become the 21st century version of our 19th century snake oil salesman.

 

Mistrust of science and rational thought have always been part of the American zeitgeist. Scientific facts are often suspect, even when friends and relatives are sick and dying. Anti-intellectualism places education below the self-made man or woman. Donald Trump’s election is only the latest example of its resilience. Unquestioning followers reject any serious analysis of Trump’s temperament and beliefs, including their effects on social and scientific questions such as income inequality and climate change. Bias and emotion take precedence over inquisitive and unbiased reasoning. We often associate these positions with the under-educated and with religious groups, the historical base of the Republican Party. But they can also come from the left as with anti-vaxxers who claim vaccines cause autism.

 

Their interpretation of our Constitutional rights reinforce their belief that individual choice is more important than the greater good: “I don’t have to self-quarantine if I don’t want to. If you chose to, that’s up to you.” They see no connection between their actions as silent virus carriers and spreading disease to others. And they fail to see the hypocrisy between demanding their right to choose how to act during this pandemic and their objections to others’ right to choose, whether it’s to have an abortion or to marry your same-sex partner. There is no critical thinking.

 

Like the fervor of partisan politics, the coronavirus pandemic has once again revealed these fissures in American society. Self-interest is at odds with a communal one. To fix this, it’s important to remember Americans share a collective purpose and future. From this shared purpose, questioning our own needs with those of others can lead to discourse. But we must be curious enough to begin this process. Doing so engenders tolerance and respect for others’ beliefs. These are the seeds of the greater good.

 

I hate Donald Trump’s indifference and arrogance. But, he is not entirely to blame for the present state of our union. Both the Democrat and Republican Parties have ignored the poor and the working class for years. Yes, the GOP has been the most egregious of late. But if we are to survive this, all of this, together, our leaders must put their personal agendas aside for our greater good. I’d like to think this pandemic, affecting all of us whether we are rich or poor, men or women, gay or straight, young or old, or white or brown, will make us see not just our shared experiences as Americans, but as humans. But it won’t be easy to erase the differences that divide us. Our history is proof of that.

 

Peddling unproven cures for the coronavirus is reckless. Thinking critically might mean the difference between life and death. After three and a half years of the Trump presidency, Donald Trump’s principal motivation is clear: his self-interest. I have no hope he will change. While I’m often shocked by his behavior, I’m never surprised. I’m fighting for the greater good now. But I’m also preparing for the worst until Trump’s circus is cancelled.

  

See the rest of the posters from the Chamomile Tea Party! Digital high res downloads are free here (click the down arrow on the lower right side of the image). Other options are available. And join our Facebook group.

 

Follow the history of our country's political intransigence from 2010-2018 through a six-part exhibit of these posters on Google Arts & Culture.

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]

  

en.wikipedia.org/wiki/Coronavirus_disease_2019

As of September 9, 2020, 190,714 Americans had died of COVID-19. Despite his public statements to the contrary, it was revealed that Donald Trump knew the virus was deadly as early as January 28, 2020. During a secret intelligence briefing, the president was told by national security advisor Robert C. O’Brien, “This will be the biggest national security threat you face in your presidency. This is going to be the roughest thing you face.” This according to Bob Woodward’s new book Rage.

 

Woodward interviewed the president 18 times for this book, recording his conversations with Trump. On February 7, the president called Woodward and said, “You just breathe the air and that’s how it’s passed. And so that’s a very tricky one. That’s a very delicate one. It’s also more deadly than even your strenuous flus. This is deadly stuff.”

 

Despite what he knew, he held 17 political rallies during this period. During these events, he downplayed the virus as no worse than the flu and said that it would soon magically disappear. He mocked people for wearing masks and tried to muzzle Dr. Anthony Fauci, an immunologist who has served as the director of the National Institute of Allergy and Infectious Diseases (NIAID) since 1984, when the doctor questioned the information the president was telling the American people about the pandemic. Trump also peddled untested cures for the coronavirus, like hydroxychloroquine, despite FDA’s and the medical establishment’s concerns. In addition, he suggested that UV light and ingesting disinfectant might cure the disease. Unsuspecting Americans drank disinfectant and died.

 

According to an article in the Washington Post, "Trump admitted to Woodward on March 19 that he deliberately minimized the danger. ‘I wanted to always play it down,’ the president said. ‘I still like playing it down, because I don’t want to create a panic.’” That’s a misguided, cruel, and deadly notion. American adults aren’t children. We certainly can handle the truth (we’ve discovered it on our own). We want and need the truth from our leaders so we are well-informed and can take appropriate precautions. Most of us didn’t believe Donald Trump and took the pandemic seriously. But many of his base believed the President when he said, “this was [the Democrats’]new hoax.”

 

Donald Trump lied to the American public. Bob Woodward has his admission on tape. Republican lawmakers have refused to criticize the president about this revelation. Despite, what we can hear Trump say on Woodward’s tape, White House press secretary Kayleigh McEnany stated, “The president never tried to downplayed the virus.” Lindsey Graham went so far as to say, “I don’t think he needs to go on TV and screaming we’re all going to die.” Once again, the Trump Administration is trying to convince the American people their “alternative facts” are facts. Four more years of these alternative facts will kill us all.

  

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san bruno, california

As of August 30, 2020, 182,896 Americans had died of COVID-19. A day later, that number rose to 183,474. Donald Trump is not responsible for the pandemic. But he is responsible for the lackadaisical and disorganized response to COVID-19. It took him 70 days to take it seriously. However, as with all things Trump, concern for Americans' lives took a back seat to his own needs. He worried as the stock market reacted to the deaths and millions unemployed. After all, the economy was supposed to be his ticket to re-election. That's what mattered most to him. And golf.

 

In his continued effort to minimize the pandemic, he began to peddle questionable and even laughable cures. First it was hydroxychloroquine, a drug used to treat malaria, rheumatoid arthritis, and lupus. The FDA has issued warnings use of this drug could cause heart problems. Then there was his suggestion that UV light and ingesting household disinfectants might cure the disease. How could we take the president seriously? Amazingly, some did and lost their lives.

 

Today, he and the Republican Party virtually ignore the pandemic. It was barely mentioned during their national convention. In fact, Larry Kudlow, White House economic advisor, referred to it in the past tense, as if it was over and done with: "It was awful. Health and economic impacts were tragic. Hardship and heartbreak were everywhere. But presidential leadership came swiftly and effectively with an extraordinary rescue for health and safety to successfully fight the COVID virus."

 

Instead, in the weeks before the election, Trump wants to focus on the protests to racial inequities taking place all over the country. As the self-described "law and order president," he takes a hard line on peaceful protesters and labels them radicals and Antifa. He's trying to attach that same label to Joe Biden, as if he's the cause of this unrest. In reality, both the pandemic and the racial unrest are happening on Trump's watch—during his administration. Instead of trying to calm the situation, he incites by supporting 17-year-old Kyle Rittenhouse's self-defense explanation for killing two people with an AR-15 rifle in Kenosha, Wisconsin. As Ed Kilgore writes in New York magazine: "Trump’s leap to the defense of Kyle Rittenhouse is either pathological or a deadly message he wants to sent [sic] to future would-be racial-justice protesters."

 

Not only is Donald Trump ignoring the pandemic, he is trying to instill fear into his base and those independent voters on the fence. He's trying to divide us in order to win the election. And, all the while, he continues to play golf as the country protests and the number of people dying is increasing every day.

  

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See the rest of the posters from the Chamomile Tea Party! Digital high res downloads are free here (click the down arrow on the lower right side of the image). Other options are available. And join our Facebook group.

 

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Newsflash: Donald Trump is a poor leader. This isn't a revelation to most Americans. When confronted with a life or death situation, he's failing us with his convoluted statements and false information. And, we thought it was bad when he tried to strong-arm Ukrainian President Volodymyr Zelenski. He has referred to COVID-19 as the "Chinese virus" because he's angry China accused the US military of concocting this plague. He's completely oblivious to the racist nature of his remarks, and is ignorant of the repercussions they are having for Asian-Americans and Asians living in this country. Personal attacks replace common sense and caution.

 

The President has likened the coronavirus to the common cold. When he falsely suggested the anti-malarial drug, hydroxychloroquine could be effective in treating the disease without any clear evidence, he put us in peril. And, in fact, one person has already died after self-medicating with that drug. Medical professionals know there are no easy answers. Developing successful drugs and vaccines takes rigorous testing. Dr. Anthony Fauci, Head of the National Institute of Allergy and Infectious Diseases, finds himself in a tough spot. He stands next to Trump as the country's medical expert and listens to the President's inaccuracies, knowing he can't just "jump in front of the microphone and push him down." Trump's need to be front and center and always right takes precedence over facts. He is the authority and anyone who challenges him with those facts is suspect.

 

Now the President is suggesting he'll loosen restrictions on self-quarantine and social distancing by Easter in order to get the country back to work. Republican Texas Lt. Governor Dan Patrick suggested the welfare of senior citizens should be sacrificed to save the country. And, rightwing commentator and former Fox News host Glenn Beck said, "I would rather have my children stay home and all of us who are over 50 go in and keep this economy going and working. Even if we all get sick, I would rather die than kill the country."

 

Why is the economy suddenly more important than the health and well-being of the people? Simple answer: the President sees "his" economy as the golden ring to his re-election. With the stock market in freefall, that ring has turned to lead. And, Trump is rightfully afraid. In addition, his hotels are losing money during this crisis. And, he has even implied his businesses could benefit from a government stimulus package. The founders of our country included the Emoluments Clause in our Constitution to prevent a government official from personally benefiting from government aid. We have come to expect this self-serving attitude from Trump. Too bad the GOP sees no problem in his actions.

 

I have learned not to trust anything the President says. He's inconsistent, minimizes the danger, and often paints an inaccurate picture of the severity of this situation. He is, and will be remembered as one of the most ineffectual and self-absorbed leaders we've ever had. I can't breathe when he sucks up all the air. And, right now, that breath of fresh air would be our country's best medicine.

 

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High-profile virologist Didier Raoult, a leading proponent of the controversial drug chloroquine as a treatment for Covid-19, says the virus is disappearing in Marseille. But the city's regional health boss says it’s far too early for such conclusions.

 

In a video on twitter on Tuesday night, the specialist in infectious diseases at Marseille university hospital declared that the virus is “gradually disappearing” in the city.

 

“There is a very significant drop in the number of positive tests and an even bigger drop among those who are tested who have no symptoms,” he says.

 

At the height of the epidemic, Raoult’s Méditerranée Infection Foundation counted 368 new cases per day. But now he says numbers are around 60 to 80.

 

“It’s possible that the epidemic will disappear in the spring", he says, "A few weeks from now, it’s possible that there will be no more cases. We don’t know why, but we see it quite often, with the majority of viral respiratory illnesses.”

 

However, the Director General of the Regional Health Agency for the Marseille area worries about such suggestions.

 

"It is far too early to make predictions about the end of the epidemic", Philippe de Mester told the French newspaper France Bleu Provence. "We know nothing about its duration, unfortunately. It is true that we have recorded a slowdown in the spread of the epidemic, but not an actual decline. The epidemic will continue and it will take a few more weeks”

 

He stressed the importance of continuing to follow the lockdown rules.

 

Raoult regularly posts videos on Twitter, communicating directly with the public and not simply to the scientific community.

 

His long hair and unconventional manner are part of the anti-establishment style he appears to cultivate and he has a growing number of followers.

 

Supporters of his treatment see him as provincial hero challenging a Parisian scientific establishment and a working doctor standing up to researchers in ivory towers.

 

He maintains that an anti-malaria drug, hydroxychloroquine, combined with the antibiotic azithromicyne, is an effective treatment for Covid-19 patients, if used before they need intensive care.

 

He has published results from his use of this approach which show considerable success but with no neutral control group for comparison, there is no conclusive proof that patients recover because of his treatment. As a result, it has not been authorised for use except in certain conditions in hospitals. The drug is known to have negative side effects but it is already used against malaria and in the treatment of Lupus and rheumatoid arthritis.

 

In an interview in Le Figaro on 3 April, Raoult was critical of today’s medical research processes.

 

He said that trial methodology established during the fight against Aids was not suitable for all situations and that the “group of people” who worked together at that time adhered to such methods too rigidly. He said that research had become too divorced from medicine.

 

Although Raoult himself is both a researcher and a clinical practitioner, he distinguished between the two, saying that as a doctor he wanted to use what seemed to work. In a health crisis, he said, lengthy trials could be shortened for a drug which is already in use.

 

Numerous other trials on hydroxychloroquine are underway but so far none which tests his exact approach.

 

It is unclear why his critics in the scientific community have not conducted such trials, to prove or disprove its effectiveness.

 

Instead the impression is given of a scientific community which is unwilling for some reason to explore certain options versus a maverick burnishing a reputation.

 

Several mostly right wing politicians have voiced support for Raoult and former health minister Philippe Douste-Blazy, a cardiologist, launched a petition to allow wider use of hydroxychloroquine.

 

In an interview with RFI on Wednesday, President Macron said he was “convinced he is a great scientist”, describing him as one of our most eminent experts. Macron has now called for rigorous trials of Raoult’s treatment approach to be conducted very soon so that its efficacy can be proved or disproved.

 

Born in Senegal, where he spent his childhood, the French doctor and researcher has maintained strong professional and emotional ties with the continent. And many African countries are already using chloroquine to treat people infected with Covid-19.

 

On 24 March, Professor Didier Raoult slammed the door on the circle of researchers who were supposed to advise the French president on the pandemic.

 

Disagreeing with the containment policy adopted by France, which favours mass screening, the iconoclastic infectiologist has just been disavowed by his peers, who are reluctant to endorse the use of hydroxychloroquine against coronavirus.

 

On Thursday 9 April, Raoult could measure the progress made when President Emmanuel Macron travelled especially to Marseilles to talk to him in order to “take stock of the question of treatment.”

 

This was a strong political gesture in favour of Raoult’s theses, whose promotion of the use of hydroxychloroquine to treat coronavirus patients has been the subject of much controversy for several weeks.

 

READ MORE: Coronavirus: 9 things to know about chloroquine

 

Pre-COVID-19 era

 

A specialist in emerging tropical infectious diseases at Marseille’s Faculty of Medical and Paramedical Sciences and at the Institut Hospitalo-Universitaire (IHU) Méditerranée Infection, the long-haired professor with the pepper and salt beard was still largely unknown to the general public at the end of February when his views on a chloroquine-based coronavirus treatment began to be heard.

 

Since then, the Frenchman has seen his media and digital fame take off. And in the ranks of its most fervent supporters, the African continent is not to be outdone.

 

Is it because the chemical compound he uses to treat his patients, hydroxychloroquine, is well known on the continent, where it has long been used to treat malaria? In two publications exposing tests carried out on some 20 patients, then on 80, the researcher and his teams conclude that “hydroxychloroquine combined with azithromycin is effective in the treatment of COVID-19”.

 

This quinine derivative is currently the subject of several studies. Those carried out by Professor Raoult have indeed aroused reservations among many experts, who reproach him for not having respected standard scientific protocols. At the end of March in France, the High Council of Public Health considered that chloroquine could be administered to patients suffering from “serious forms” of the coronavirus.”

 

READ MORE: To fight coronavirus, Burkina Faso is tempted by chloroquine

 

Those African countries that opt for chloroquine

 

At Fann Hospital in Dakar, Professor Moussa Seydi, head of the department of infectious and tropical diseases, has already administered chloroquine alone to the first 100 patients who tested positive for COVID-19. “In Marseille, Dr Didier Raoult published encouraging preliminary results. The combination of hydroxychloroquine and azithromycin should make it possible to shorten the carrying time [of the virus], in order to accelerate the healing of the sick,” Seydi told Jeune Afrique on 19 March. To use this drug, he says he relied on the study co-signed by his French counterpart.

 

Like Senegal, Burkina Faso, Algeria and Morocco have also opted for chloroquine.

 

On 23 March, the Ministry of Health of the Cherifian Kingdom thus requisitioned the national stocks and distributed to the directors of CHU the protocol for the prescription of chloroquine and hydroxychloroquine for confirmed cases of COVID-19. A decision inspired by Chinese research on the subject, and studies conducted by the French researcher, according to a member of the Moroccan committee in charge of the fight against the pandemic.

 

Born and raised in Senegal

 

If Professor Raoult is well known on the continent, it is also because this specialist in tropical and infectious diseases, in addition to having grown up there, has worked a lot there. It was in Dakar that the Frenchman is said to have caught the research virus.

 

Born in 1952 in the Senegalese capital, he lives there, in the building of the Research Office for Food and African Nutrition (Orana), created by his father.

 

This building sits opposite the Pasteur Institute in Dakar which houses the frontline laboratory in the fight against the epidemic in Senegal, and is where this son of a nurse and a military doctor stationed at the capital’s main hospital, took his first steps.

 

A childhood marked by happy memories of playing on the beach at Anse Bernard, made the move “complicated” when the young Didier Raoult arrived in Marseille at the age of 9. “Being partly Senegalese, I can’t help but feel concerned by what’s happening in Africa,” he says in a video addressed to the Senegalese group eMédia on 7 April.

 

QUEST FOR CHLOROQUINE

Coronavirus: Didier Raoult the African and chloroquine, from Dakar to Brazzaville

By Marième Soumaré, Rémy Darras

Posted on Wednesday, 15 April 2020 19:39

 

didier raoult

Professor Didier Raoult with Doctor Cheikh Sokhna (in the yellow shirt) in Niokolo-Koba park in Senegal, August 2019 © DR

Born in Senegal, where he spent his childhood, the French doctor and researcher has maintained strong professional and emotional ties with the continent. And many African countries are already using chloroquine to treat people infected with Covid-19.

 

On 24 March, Professor Didier Raoult slammed the door on the circle of researchers who were supposed to advise the French president on the pandemic.

 

Disagreeing with the containment policy adopted by France, which favours mass screening, the iconoclastic infectiologist has just been disavowed by his peers, who are reluctant to endorse the use of hydroxychloroquine against coronavirus.

 

On Thursday 9 April, Raoult could measure the progress made when President Emmanuel Macron travelled especially to Marseilles to talk to him in order to “take stock of the question of treatment.”

 

This was a strong political gesture in favour of Raoult’s theses, whose promotion of the use of hydroxychloroquine to treat coronavirus patients has been the subject of much controversy for several weeks.

 

READ MORE: Coronavirus: 9 things to know about chloroquine

 

Pre-COVID-19 era

 

A specialist in emerging tropical infectious diseases at Marseille’s Faculty of Medical and Paramedical Sciences and at the Institut Hospitalo-Universitaire (IHU) Méditerranée Infection, the long-haired professor with the pepper and salt beard was still largely unknown to the general public at the end of February when his views on a chloroquine-based coronavirus treatment began to be heard.

 

Since then, the Frenchman has seen his media and digital fame take off. And in the ranks of its most fervent supporters, the African continent is not to be outdone.

 

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Is it because the chemical compound he uses to treat his patients, hydroxychloroquine, is well known on the continent, where it has long been used to treat malaria? In two publications exposing tests carried out on some 20 patients, then on 80, the researcher and his teams conclude that “hydroxychloroquine combined with azithromycin is effective in the treatment of COVID-19”.

 

This quinine derivative is currently the subject of several studies. Those carried out by Professor Raoult have indeed aroused reservations among many experts, who reproach him for not having respected standard scientific protocols. At the end of March in France, the High Council of Public Health considered that chloroquine could be administered to patients suffering from “serious forms” of the coronavirus.”

 

READ MORE: To fight coronavirus, Burkina Faso is tempted by chloroquine

 

Those African countries that opt for chloroquine

 

At Fann Hospital in Dakar, Professor Moussa Seydi, head of the department of infectious and tropical diseases, has already administered chloroquine alone to the first 100 patients who tested positive for COVID-19. “In Marseille, Dr Didier Raoult published encouraging preliminary results. The combination of hydroxychloroquine and azithromycin should make it possible to shorten the carrying time [of the virus], in order to accelerate the healing of the sick,” Seydi told Jeune Afrique on 19 March. To use this drug, he says he relied on the study co-signed by his French counterpart.

 

Like Senegal, Burkina Faso, Algeria and Morocco have also opted for chloroquine.

 

On 23 March, the Ministry of Health of the Cherifian Kingdom thus requisitioned the national stocks and distributed to the directors of CHU the protocol for the prescription of chloroquine and hydroxychloroquine for confirmed cases of COVID-19. A decision inspired by Chinese research on the subject, and studies conducted by the French researcher, according to a member of the Moroccan committee in charge of the fight against the pandemic.

 

Born and raised in Senegal

 

If Professor Raoult is well known on the continent, it is also because this specialist in tropical and infectious diseases, in addition to having grown up there, has worked a lot there. It was in Dakar that the Frenchman is said to have caught the research virus.

 

Born in 1952 in the Senegalese capital, he lives there, in the building of the Research Office for Food and African Nutrition (Orana), created by his father.

 

This building sits opposite the Pasteur Institute in Dakar which houses the frontline laboratory in the fight against the epidemic in Senegal, and is where this son of a nurse and a military doctor stationed at the capital’s main hospital, took his first steps.

 

A childhood marked by happy memories of playing on the beach at Anse Bernard, made the move “complicated” when the young Didier Raoult arrived in Marseille at the age of 9. “Being partly Senegalese, I can’t help but feel concerned by what’s happening in Africa,” he says in a video addressed to the Senegalese group eMédia on 7 April.

 

The article continues below

 

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In 2008, Raoult established a joint research unit at his IHU in the Senegalese capital dedicated to communicable infectious diseases – one of Raoult’s two African teams with the Algiers team. The latter claims to produce 10% of scientific publications in the country of Teranga. “He wanted to have a lot of field staff: epidemiologists, virologists and bacteriologists,” explains one of his close friends, epidemiologist and biologist Cheikh Sokhna, team leader at the IHU Méditerranée Infection in Marseille.

 

READ MORE: To fight coronavirus, Burkina Faso is tempted by chloroquine

 

Research on all fronts

 

Sokhna, also a Senegalese, is director of research at the Institut de recherche pour le développement (IRD), and regularly exchanges with Professor Raoult. This week, IHU’s Senegalese team of about thirty people was due to submit a research project to the Senegalese Ministry of Health on the protocol of the chloroquine-azithromycin combination.

 

An encouraging sign, according to Sokhna, is that the prevalence of coronavirus seems to be lower in areas where the use of antimalarial drugs such as chloroquine or mefloquine is frequent.

 

“This can be seen very crudely. But other factors will have to be taken into account before any definitive conclusions can be drawn,” adds the enthusiastic and cautious researcher, who is usually based in Marseille but is currently on a long-term mission in Dakar.

 

This mixed research unit is far from being the only innovation driven by Didier Raoult in Africa. In 2012, the French researcher installed a MALDI-TOF at the main hospital in Dakar: a mass spectrometer that can detect bacteria in a few hours, compared to the usual two to three days with traditional methods.

 

Then, starting in 2015, he set up three small laboratories in Dakar and two villages in the Fatick region (Centre-West), three small laboratories – points of care (POC), in the jargon of the milieu – which allow blood or saliva to be taken and the origin of the disease or fever to be quickly given so that the nurses can propose an effective remedy in good time.

 

Didier Raoult launches research all over Senegal. On malaria, borreliosis, rickettsiosis, malnutrition, hand washing – “which can reduce diarrhoeal diseases by 50% and respiratory diseases by 30%”. The French doctor was already working with his Senegalese teams on other less severe forms of the coronavirus family that existed in the country, causing colds and pneumopathies.

 

READ MORE: Top 10 coronavirus fake news items

 

“Big African brother”

 

Every year, since 2008, he comes to spend a week in Dakar, participating in the IRD’s scientific day organized by Cheikh Sokhna, which brings together health actors and NGOs. It was on this occasion that he met two renowned scientists: the parasitologist Oumar Gaye, from the Cheikh-Anta-Diop University of Dakar (Ucad), and the pharmacist-colonel Souleymane Mboup, virologist and bacteriologist. They will join the scientific board of the IHU Méditerranée Infection, where the second will succeed the first.

 

All these names join the large community of African researchers gathered around the Marseille-based professor, including the Congolese Jean Akiana, from the Marien Ngouabi University in Brazzaville, the Algerian Idir Bitam, from the National Veterinary College in Algiers, and the Malian Ogobara Doumbo (who died in 2018). They all consider their peer as a “big African brother”. Not to mention his former doctoral students, with whom he has plans to create cutting-edge laboratories in Guinea-Conakry.

 

Described as an anti-conformist in the fight against dogma, familiar with the terrain but resistant to the beaten track, Professor Raoult does not hesitate to travel to the African countryside. “It’s an elephant that likes to come into contact with gorillas,” says Dr. Jean Akiana, director of health technologies at the Ministry of Health and a researcher at the National Public Health Laboratory in Brazzaville.

 

Interested in the transmission of bacteria from animals to humans, and vice versa, Raoult also went to meet gorillas in the Lésio-Louna reserve, in the Pool region, in south-eastern Congo-Brazzaville, to analyse their microorganisms and compare their residues with human faeces. “Picornavirus of the same family as coronavirus was found in the gorillas’ faeces. If we see Ebola genes, it could be a warning,” says Jean Akiana.

 

Akiana recently received a credit from Professor Raoult’s laboratory to travel to the Tchimpounga reserve to check whether chimpanzees might be the cause of the wild polio virus that struck Pointe-Noire in 2015. The Marseille-based professor also travelled to several departments such as Likouala, Sangha and the Plateaux to prospect for new micro-organisms with no immediate link to an identified outbreak. Samples that, when examined in Marseille, could help to take the lead when new epidemics occur.

 

In Algiers, a team made up of 100% Algerian teaching and research staff, is working on the final establishment of a research laboratory. The joint unit based in the Algerian capital is also working on infectious disease surveillance, taking advantage of the facilities of the Marseille-based institute.

 

Without foreigners, “no science in France”

 

“Its main objective is to help French-speaking countries, to transfer cutting-edge technology and to train young researchers in these innovative diagnostic tools,” says Sokhna. But Raoult, on the other hand, also knows very well what his country’s science owes to the African continent.

 

Critical of the restrictions imposed by the French administration in terms of the time it takes to obtain a visa, he believes that today the French scientific community relies above all on the contribution of doctoral students from the Maghreb and sub-Saharan Africa. During Emmanuel Macron’s visit, the Head of State was welcomed by a team of young researchers from Algeria, Morocco, Mali and Burkina Faso.

 

“In France, 50% of PhD students are foreigners. Without foreigners, there is no French science,” Raoult pointed out at a conference in 2013. At the time, the French researcher praised the work of the émigrés who are part of his team, the “engine of war” in scientific research. “The best, the most intelligent, the most dynamic, those who work on Sundays are only Sub-Saharan Africans and North Africans. That’s it! That’s the way it is.”

 

READ MORE: Coronavirus: Ending Europe’s colonial approach to medicine in Africa

 

Free spirit

 

The theme of the conference? “Disobedience at the heart of the research innovation process”. Raoult is known for not embarrassing himself in manners and freeing himself from doctrine, insulted by some, adulated by others, Raoult is a lasting figure. And he doesn’t seem to care. “I couldn’t imagine [my studies] triggering passions of this nature, I don’t even know where they come from,” he says in a video posted online on 8 April, in which he announces the imminent results of his new study, this time involving 1,000 patients.

 

According to the French press, the professor would have presented last Thursday to Emmanuel Macron his results, which establish a rate of virological cure of his patients of more than 91%. Accustomed to not being listened to by politicians, who take researchers “for strange birds”, Professor Raoult, says he is “guided by curiosity and exploratory research”.

 

Will he be able to rally Macron to his cause? In a recent Odoxa barometer, Raoult the iconoclast, appears in any case in second place among the favourite personalities of the French.

 

www.theafricareport.com/26264/coronavirus-didier-raoult-t...

  

In a March 2023 interview with Kentucky Senator Rand Paul, Fox Business host Maria Bartiromo continued to push ivermectin and hydroxychloroquine as effective against COVID-19 (even Senator Paul refused to take the bait). Watch the interview.

 

Americans have lost confidence in their government. We no longer trust our legislators and the Supreme Court to solve our country’s problems: income inequality, affordable health care, a woman’s right to decide what’s best for her health, the economy, and climate change. Governance has become a series of battles. It’s no longer just political ideology. We are at war over cultural issues while our politicians ignore our basic needs. And we’ve lost faith in our country’s institutions when ersatz news organizations like Fox knew Donald Trump lost the election but promoted voter fraud to get ratings.

 

The morals of our GOP legislators and their sycophants are just as important as their economic policy. How can we trust a party that Alex Patton, a Florida-based Republican consultant, and pollster, has characterized as a party that “has become mean and driven by emotion on whom we dislike.”? “But,” he says, “that is the driving force in American politics right now.” That is the driving force of the GOP, not the Democrats. This is not an example of the equality of “bothsidesism.”

 

In my essay, “ It’s Time to Release Our Own Kraken!” I outlined the history of the Republican Party’s “below the belt” tactics. They continue to be underhanded to this day. But with the low level of civility in our present polarized country, many Republican legislators now in office have hit new ethical lows.

 

As a visual artist who has spent over a decade creating posters about the sorry state of American political discourse, this year I began a new series of portraits, “Faces of the Republican Party.” The men and women in this series deserve to be taken to task for their unwillingness to compromise, belief in conspiracy theories, and disdain for the LGBTQ+ community, women’s rights, and our children’s education. The purpose of our government is to solve our nation’s problems. It’s not a place for personal vendettas or manufactured cultural issues.

 

“Faces of the Republican Party” is not a partisan series of portraits. Merriam-Webster defines the word as “a firm adherent to a party, faction, cause, or person, especially one exhibiting blind, prejudiced, and unreasoning allegiance.” The people depicted in these images are the partisans. Instead, my series is a documentary and op-ed showcasing the facts in 2022. All of them had a hand in trying to overthrow the government. These images are MAGA Republicans who put their blind allegiance to Donald Trump and their careers ahead of the needs of the American people.

 

The results of the 2022 midterm elections showed we are tired of autocratic and self-absorbed politicians. We would simply like our officials to do the jobs we elected them to do. Everyone deserves a piece of American Exceptionalism. As it stands, there is nothing exceptional about the tribalism these people promote.

 

Republicans are perfect examples of Patton’s “driving force.” This force is dirty, mean, misogynistic, selfish, and wastes our tax dollars. These people are just a small sampling of individuals responsible for the loss of credibility and faith in America’s institutions. And worse, they couldn’t care less.

  

Feel free to pass this poster on. It's free to download here (click on the down arrow just to the lower right of the image). Each has a special Creative Common's copyright that allows you to share these images as long as there is attribution, no derivatives, and you do not use these for commercial purposes.

 

See the rest of the posters from the Chamomile Tea Party! Digital high res downloads are free here (click the down arrow on the lower right side of the image). Other options are available. And join our Facebook group.

 

Follow the history of our country's political intransigence from 2010 to 2020 through a eight-part exhibit of these posters on Google Arts & Culture.

 

www.cnn.com/2020/07/02/health/hydroxychloroquine-coronavi... Before making any statements our mass media must be sure that information comes from credible & reliable sources. I understand that CNN may not be the best for the info but the fact that Hydroxychloroquine could save lives was medically proven from 2006 ! And other non-medical info as well !!!

...riding outside inside a bicycle.

If Nerd Immunity goes wrong ...

 

4.4.2020: www.youtube.com/watch?v=zer6omW0vnU

Toronto, Canda. Hydroxychloroquine, prescription for Lupus or Rheumatoid Arthritis, being pushed by Donald Trump as a possible drug to combat #Covid19, with no evidence © Linda Dawn Hammond/ IndyFoto April 19, 2020.

 

Photo by Samuel Corum for The New York Times.

 

Article by Maureen Dowd in The New York Times :

 

Macbeth has his doubts.

 

But his wife taunts him about his manliness until he bloodies his country.

 

It’s hard to believe, four centuries after Shakespeare, that the fear of being unmanned is still so potent that it could wreck a country.

 

But it is. And it has.

 

Donald Drumpf’s warped view of masculinity has warped this nation’s response to a deadly pandemic. And Drumpf doesn’t even have a diabolical Lady MacTrump whispering in his ear, goading him about being a man. He goads himself, fueled by ghostly memories of his autocratic father.

 

As the Shakespeare scholar Stephen Greenblatt writes: “The tyrant, Macbeth and other plays suggest, is driven by a range of sexual anxieties: a compulsive need to prove his manhood, dread of impotence, a nagging apprehension that he will not be found sufficiently attractive or powerful, a fear of failure. Hence the penchant for bullying, the vicious misogyny, and the explosive violence. Hence, too, the vulnerability to taunts. Especially those bearing a latent or explicit sexual charge.”

 

Drumpf’s fear of emasculation led to his de-mask-ulation. Instead of cleaving to science and reason, he stuck with the old, corny Gordon Gekko routine, putting concern for the stock market above all else.

 

Like Macbeth, the president made tragic errors of judgment and plunged his country into a nightmare. Our trust in government is depleted, and our relationships in the world are tattered. As Fintan O’Toole wrote in The Irish Times, the world has loved, hated and envied the United States. But never before has it pitied us. Until now.

 

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Drumpf has always said that the whole world is laughing at us because it’s taking advantage of us. That sound you’re hearing is not laughter.

 

“He could be on his way to re-election now if he had done what many of the governors did and followed science and public health advice and if he had leveled with people about what the requirements were and why,’’ says David Axelrod, the former Obama strategist. “If he had done those things, the country would have responded and been in a much better place.

 

“But he didn’t have the emotional capacity to do it. At a minimum, it’s Shakespearean. It’s almost biblical.”

 

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Even Drumpf’s allies are baffled about why he can’t fake a sense of compassion and competency. He has made enough cheesy movie cameos — even one hawking cheese-stuffed Pizza Hut crust — that he should know how to pretend to be halfway human.

 

Now the president is threatening another crisis, tweeting that we might have to delay the election because there could be mail-in voting fraud.

 

In his view, either he wins or the election is rigged. He’s trying to make mail-in ballots socially unacceptable the same way he made masks socially unacceptable for the first five months of the plague.

 

The Washington Post reports that backlogs at the U.S. Postal Service are causing some employees there to worry that the Drumpf lackey in charge, a top donor, is intentionally gumming up the works just in time for the election. It is astounding the corrupt lengths the administration seems willing to go to — destroying the Postal Service to win the election. Ben Franklin would be incensed.

 

As Axelrod notes, “Whatever happened back in the Bush v. Gore recount days will seem like the Garden of Innocence compared to what’s going to happen now. Drumpf is not going to walk to the rostrum and say, ‘The people have spoken and I accept their verdict.’’’

 

Even Drumpf’s closest allies in Congress, Mitch McConnell and Kevin McCarthy, couldn’t stomach the idea of postponing the election, and both have swallowed a lot over the last three years. Drumpf’s little trial balloon blew up like the Hindenburg.

 

Alexander Burns wrote in The New York Times that Drumpf was too pathetic to be a tyrant: “Far from a strongman, Mr. Drumpf has lately become a heckler in his own government, promoting medical conspiracy theories on social media, playing no constructive role in either the management of the coronavirus pandemic or the negotiation of an economic rescue plan in Congress — and complaining endlessly about the unfairness of it all.”

 

Talk about unfair: The one thing holding the country together has been the additional $600 per week in unemployment benefits that has allowed millions to pay the rent and fill the fridge. Republicans, though, are so convinced that the few extra hundred dollars in jobless pay is keeping people from work that they are loath to renew it. Unless Congress gets it together soon and finds a way to extend the aid, the country is going to be facing a catastrophe of homelessness and need that makes these past few months look pleasant.

 

After the president began doing the coronavirus briefings again, he tried a “new” tone, saying he was getting used to masks — “Think about patriotism. Maybe it helps. It helps” — then face-planting by offering good wishes to a past party pal and accused pedophile enabler, Ghislaine Maxwell. But then things got really crazy as he defended a retweet of a doctor who has promoted hydroxychloroquine as well as declaimed on the existence of alien D.N.A. and demon sperm.

 

“I thought her voice was an important voice, but I know nothing about her,’’ he told reporters. (As he told Barstool sports: “It’s the retweets that get you in trouble.”) He fell into more self-pity, complaining about his ratings compared to those of Dr. Anthony Fauci: “Nobody likes me. It can only be my personality, that’s all.”

 

It has been clear for some time that Drumpf’s Panglossian attitude toward the virus was turning him into a public health menace.

 

But this week, the culture war over masks crystallized with the death of Herman Cain. The former Republican presidential candidate, who dissed masks and Covid restrictions, proudly tweeted a picture from the Drumpf rally in Tulsa, surrounded by his fellow mask-less friends. “Having a fantastic time,” he wrote. Nine days later, he tested positive for corona. As we have learned, this virus often has the final say.

 

Right away, White House officials knew that this death would be laid at Drumpf’s feet. They began warning reporters that they should not politicize Cain’s death.

 

At the Friday White House briefing, asked if officials were concerned that the 74-year-old Cain may have contracted the virus at the rally, Kayleigh McEnany replied, “We’ll never know,” and sanctimoniously added, “I will not politicize Herman Cain’s passing.’’

 

But it is undeniable that Drumpf politicized masks and set a lethal example.

 

As Jeremy Peters wrote in The Times, Republican officials all over the country “have adopted a similar tone of skepticism and defiance, rejecting the advice of public health officials and deferring instead to principles they said were equally important: conservative values of economic freedom and personal liberty.”

 

So conservatives are willing to embrace a new ethos? Give me liberty. And death.

www.youtube.com/watch?v=MkQK83Tf9so&ab_channel=Queen-...

 

www.youtube.com/watch?v=XpdpW0z9xnQ&ab_channel=Shuffl...

 

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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

If you wanna ignore the findings of the French study on the efficacy of hydroxychloroquine against COVID-19, well... "Freedom to try" might be freedom to die.

 

Chevy Sportvan

parked at Ralph's Thriftway supermarket

in Olympia, Washington

The American President shows off his preferred drug of choice to treat COVID-19 novel coronavirus.

 

After all, the hydroxychloroquine + azithromycin combination didn't work out like he'd hoped, so maybe Lysol® will.

 

His remarks were NOT sarcastic as he had so claimed today (he had turned to and was addressing a physician, Dr. Deborah Birx, MD – and WHY is he joking about a disease that has sickened and killed so many?), when he made his absurd remarks as follows:

 

"And then I see the disinfectant, where it knocks it out in a minute. One minute. And is there a way we can do something like that, by injection inside or almost a cleaning. Because you see it gets in the lungs and it does a tremendous number on the lungs. So it would be interesting to check that. So, that, you’re going to have to use medical doctors with. But it sounds — it sounds interesting to me. So we’ll see. But the whole concept of the light, the way it kills it in one minute, that’s — that’s pretty powerful."

 

Four more years, anyone?

 

Just for context, for those who may be blissfully unaware of the damage being done to our nation's most vulnerable members, and the corresponding economic devastation which has exposed how he's decimated American preparedness (Puerto Rico STILL hasn't begun an adequate recovery from Hurricane Maria, but those paper towels he tossed sure were a help!) by the novel (new) coronavirus monikered as COVID-19.

 

Our economy will eventually recover, but the lives which have been lost under his watch will be gone forever.

 

Here's the reference video.

youtu.be/bATddhoI6gI?t=1593

What flavour will you be/not getting?

 

www.youtube.com/watch?v=1VcAs2UuotI&ab_channel=IDLES

 

#Oxford-Astrazeneca

#Pfizer-BioNTech

#Moderna

#Johnson/Johnson

#Sinopharm

#Sputnik-V

#Sinovac

#Janssen

#EpiVacCorona

#Covaxin (Bharat Biotech)

#CanSino

 

#TheAlphaSquad

#TheBetaSquad

#TheDeltaSquad

#TheOmegaSquad

#TheSigmaSquad

#BotswanaVariant.Omicron (B.1.1.529)

#BrazilianVariant (P.1)

#ColumbianVariant-Mu (B.1.621)

#IndianVariant (B.1.617.2)

#PeruvianVariant-Lambda (C.37)

#SouthAfricanVariant (B.1.351)

#UnitedKingdomVariant (B.1.1.7)

#USAVariant-Epsilon (B.1.429)

#USAVariant-Kraken (XBB.1.5)

 

In the history of virology there has never ever been a viral mutation that resulted in a virus that was more lethal.

 

As viruses mutate they become more contagious, transmissible but always less lethal.

 

#TheNudgeUnit

#FactsNotFear

#HIV

#Monkeypox

#VariantMutation

#Smallpox

#Shingles

#EnteroVirus

#MarburgVirus

#DiedSuddenly

#Covid21

#Corona

#Florona

#Flurona

#MySharona

#TripleCovid

 

10 Questions To Ask Yourself Before Getting The Covid Jab.

 

1: If I get vaccinated can I stop wearing a mask(s)?

 

Government: "NO"

 

2: If I get vaccinated will I be resistant to Covid?

 

Government: "Maybe. We don't know exactly, but probably not."

 

3: If I get vaccinated, at least I won't be contagious to others - right?

 

Government: "NO". The vaccine doesn’t stop transmission."

 

4: If I get vaccinated, how long will the vaccine last?

 

Government: "No one knows. All Covid "vaccines" are still in the experimental stage."

 

5: If I get vaccinated, can I stop social distancing?

 

Government: "NO"

 

6: So what's the benefit of getting vaccinated?

 

Government: "Hoping that the virus won't kill you."

 

7: Are you sure the vaccine won't injure or kill me?

 

Government: "NO"

 

8: If statistically the virus won't kill me (99.7% survival rate), why should I get vaccinated?

 

Government: "To protect others."

 

9: If I get vaccinated, I can protect 100% of people I come in contact with?"

 

Government: "NO"

 

10: If I experience a severe adverse reaction, long term effects (still unknown) or die from the vaccine will I (or my family) be compensated from the vaccine manufacturer or the Government?

 

Government: "NO - the government and vaccine manufacturers have 100% zero liability regarding this experimental drug"

 

In summary, the Covid19 vaccine...

 

•Does not provide immunity.

 

•Does not eliminate the virus.

 

•Does not prevent death.

 

•Does not guarantee you won’t get it.

 

•Does not stop you from passing it on to others.

 

•Does not eliminate the need for travel bans.

 

•Does not eliminate the need for business closures.

 

•Does not eliminate the need for lockdowns.

 

•Does not eliminate the need for masking.

 

If you still believe in the mainstream narrative, I have a few questions and can’t wait for a public enquiry.

 

Explain how the flu disappeared but has been replaced with something which has the EXACT same symptoms.

 

Explain why they downgraded "Covid-19" from a high consequential infectious disease days before they declared a pandemic. March 2020 gov website.

 

Explain how they pulled the coronavirus Act 2020 legislation together in a matter of days, despite the act being several hundred pages long.

 

Explain why they have completely changed normal practice and used criteria like "deaths for a reason within 28 days of a positive test" to classify a Covid-19 death.

 

Explain why they banned autopsies of anyone dying from/with Covid-19.

 

Explain why they changed the law to allow any practitioner to diagnose Covid through observation alone, even if it is done through video consultation.

 

Explain how all cause mortality is at an all time low.

 

Explain how millions of protesters across the globe aren't getting sick with "Covid."

 

Explain how this is the only crisis that needs an advertising campaign paired with a constant barrage of repetitive brainwashing propaganda on the TV and in the streets.

 

Explain how hundreds of thousands of people marched through the streets of London, Paris, Sydney and Berlin for an afternoon last month but it wasn't once shown on any TV channel or reported in the mainstream press and still continue to do so.

 

Explain how thousands were yelling "shame on you" outside the BBC HQ in both London, Manchester and Cardiff but it wasn't shown on the TV?

 

Explain how the people who are wearing the masks and following the rules are the only ones who are catching "COVID".

 

Explain how the creator of the PCR amplification tool is on record for stating that the PCR was not designed as a test for infectious diseases.

 

Explain why they are using the PCR to diagnose an infectious disease.

 

Explain why the concern has been changed from Covid deaths, to hospitalisations to Covid infections to Covid "cases".

 

Explain how the "anti-vaxxers" are being blamed for the rise in "cases" when the only people who could possibly be contributing to the statistics are the people who are getting the "test" in the first place.

 

Explain why the hospitals were emptier than normal during the height of the "pandemic."

 

Explain why whistleblowers are reporting that the hospitals are now filling up with vaccine adverse reactions but the MSM are not reporting it.

 

Explain why kids need to be vaccinated when, by your own definitions, Covid isn't dangerous to children.

 

Explain, if all the vulnerable people have already been vaccinated, why do all the healthy people need to get vaccinated if you're already protected by your own vaccine and the recovery rate was already 99.96% without the vaccine.

 

Explain why the average age of death with "Covid" (82.4 years) is higher than the average age of death without (81.5 years).

 

Explain how you can get banned from Facebook and Twitter for sharing official government links.

 

Explain why there are several class actions in progress, taking governments across the globe to court for crimes against humanity, but there is zero MSM coverage.

 

Explain why most government leaders are reading from the same script and going to extreme unjust lengths to keep their public at home.

 

Canada, Italy, Israel, Australia and New Zealand are the five countries using the most strictest of measures and demanding proof of double/triple vaccination status, with Austria, Germany, Holland and France to follow suit later in the year. All planned and mapped out so it seems.?

 

Explain how all the things that you were laughing at us for talking about last year are now becoming a reality this year.

 

From laboratory released virus, gain of function research, operation warp speed to vaccine passports and mass surveillance, (via NHS app).

 

Mutation variants from leaky vaccines to constantly keep this shit train on track for at least a couple more years, a new strain of bullshit and third wave of propaganda producing an annual/quarterly covid shot? let's wait and see on that? It would not surprise me in the slightest. Yawn.

 

In my own personal opinion this was never about a virus but everything to do with the vaccination. How long will it take society to turn on the unvaccinated? Or will the human spirit prevail.?

 

Society is so easy to divide when you really think about it. Sex, Identity, Pronoun, Race, Politics, Colour, Religion, Post/Zip Code, Country, Bank Balance, City, Province, Sport, Team, Car, Technology, Holiday Destination, Vaccinated, Even how early you wake up, etc. etc. Too many to list!

 

It is endless and we all collectively fall for it, time, over time again.

 

When the U.K becomes 90% double vaccinated of ages between 16 to 80 that is when you will more than likely see a push for a social divide, I could be wrong? I sometimes am. It is April now, warp speed is in full effect so let's just wait and see what polygon kayfabe clown fear porn is happening come December 2021.

 

(Plan B)

 

Tick tock.........

 

www.youtube.com/watch?v=5GC_X_tI5kA&ab_channel=Dakota...

 

Anti-Vaxxer: Noun, Informal.

 

1. A person who trusts their own immune system more than they trust pharmaceutical companies, career politicians and the corporate media.

 

(See also: critical thinker)

 

Over 25 countries have less than 15% of their population vaccinated. Where are the millions of dead people?

 

Burundi: population 11 million Vaccination rate: 0.1%

 

Congo: population 89 million Vaccination rate: 0.3%

 

Haiti: Population 11 million Vaccination rate: 0.9%

 

Chad: Population 16 million Vaccination rate: 0.9%

 

Yemen: population 29 million Vaccination rate: 1.3%

 

Ethiopia: Population 115 million Vaccination rate: 1.6%

 

South Sudan: Population 11 million Vaccination rate: 2.5%

 

Cameroon: population 26 million: Vaccination rate: 2.6%

 

Papua New Guinea: Pop: 9 million Vaccination rate: 2.7%

 

Nigeria: Population 206 million Vaccination rate: 2.7%

 

Madagascar: Population 26 million. Vaccination rate: 3.4%

 

Tanzania: Population 59 million. Vaccination rate: 3%

 

Mali: population: 20 million Vaccination rate: 3.6%

 

Burkina Faso: population 20 million Vaccination rate: 3.8%

 

Malawi: population 19 million Vaccination rate: 4.2%

 

Niger: population 24 million Vaccination rate: 4.4%

 

Sudan: Population 43 million Vaccination rate: 4.6%

 

Uganda: population 45 million Vaccination rate: 5%

 

Senegal: population 16 million Vaccination rate: 6.2%

 

Algeria: Population 43 million Vaccination rate: 14%

 

Kenya: Population 53 million Vaccination rate: 14%

 

Zambia: Population 18 million Vaccination rate: 10%

 

These countries have a combined population of over 900 million people and over 90% of them are unvaccinated. Where are the mass graves? Most of them didn't even lockdown or have social distancing or mask mandates.

 

The vaccines have nothing to do with Covid or any virus. It is a bio-weapon.

 

Papua New Guinea: Population 9 million Vaccination rate: 2.7% Obesity rate is 30% which is higher than Canada and Europe.

 

In a real pandemic most of the deaths are among children under the age of 5 because they have immature immune systems. Most of these countries have younger populations which means their death rate should be much higher than Europe and North America.

 

They also have relatively poor living conditions which means poor hygiene. Millions and millions of young children should be dead by now if it was a real pandemic.

 

An avalanche of names who are helping destroy humanity.

 

Larry Page, Google.

Bill Gates, Microsoft.

Feike Sijbesma, Philco.

Queen Rania of Jordan.

Al Gore, Environmentalist.

Luis Alberto Moreno, WEF.

Thomas Buberl, CEO, AXA.

Heizo Takenaka, Economist.

Julie Sweet, CEO, Accenture.

Mark Schneider, CEO, Nestlé.

Herman Gref, CEO, Sberbank.

L. Rafael Reif, President of MIT.

Arvind Krishna. Chairman of IBM.

Robert Mercer, Renaissance Fund.

Mark Zuckerberg, Facebook/Meta.

Peter Maurer, President, Red Cross.

Dustin Moskovitz, Open Philanthropy.

Angel Gurría, Secretary General OECD.

Zhu Min, Deputy Managing Director, IMF.

Fabiola Gianotti, Director General, CERN.

Orit Gadiesh, Chairman, Bain & Company.

Laurence Fink, Chairman & CEO, BlackRock.

Mukesh D. Ambani, Chairman, Reliance Industries.

Mark Carney, UN Special Envoy for Climate Action.

Kristalina Georgieva, Managing Director of the IMF

Dr.Anthony Fauci. Chief Medical Adviser to POTUS.

André Hoffmann, Vice-Chairman Hoffman-La Roche.

Christine Lagarde, President, European Central Bank.

Patrice Motsepe, Chairman, African Rainbow Minerals.

Klaus Schwab, Founder and Executive Chairman, WEF.

Tharman Shanmugaratnam, Defense Minister, Singapore.

Marc Benioff, Chair and Chief Executive Officer, Salesforce.

Jim Hagemann Snabe, Chairman of Siemens and of Maersk.

Paula Ingabire, Minister of Info Communication Tech Rwanda.

 

Peter Brabeck-Letmathe, Vice-Chairman of the Board of Trustees WEF.

 

Chrystia Freeland, Deputy Prime Minister and Minister of Finance, Canada.

 

David M. Rubenstein, Co-Founder & Executive Chairman, Carlyle Group.

  

www.youtube.com/watch?v=f--QTXpb0QI&ab_channel=Courtn...

...some Donald dude with a 9-iron in the rough said this water was the best water.

Hydroxychloroquine 3D molecular structure (Jmol). Firefly 8.2.0 PM3 energy minimum (no imaginary frequencies). Heat of formation = -29.41 kcal/mol. C-N-C=C torsion angle = 72.09 degrees. Legend: carbon atom: grey; hydrogen, white; nitrogen, blue; oxygen, red; chlorine, green. It is also known as Plaquenil (HCQ sulfate). C18H26ClN3O (freebase).

 

Although an early COVID-19 clinical trial using anti-malarial (±)-hydroxychloroquine (HCQ) was thought to show promise (especially when combined with azithromycin), more exhaustive global studies found no overall benefit.

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

Toronto, Canada. Justice in a mask. Days of #Covid19 © Linda Dawn Hammond/ IndyFoto April 19, 2020.

 

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

...some Donald dude with a 9-iron in the rough said this water was the best water.

It's Only A Matter Of Time!

I didn't create this image. I added some text to a screen grab of a video clip on youtube HERE: www.youtube.com/watch?v=Mb9tnUi78MM

 

Please don't drink hydroxychloroquine or Aquarium Cleaner, don't drink cleaning products or insert UV lamps. It could be fatal.

Don't believe everything that you hear from This President. www.youtube.com/watch?v=vA_39Yqb0QA

 

Get the BIG picture of the outbreak HERE: gisanddata.maps.arcgis.com/apps/opsdashboard/index.html#/...

 

Stay safe All & best wishes.

Peace.

holistichealth.one/natural-hydroxychloroquine-and-ivermec... Natural Alternatives to Hydroxychloroquine and Ivermectin. You won't get a prescription from a medical doctor because these medicines actually work unlike vaccines. Learn how to protect yourself from covid-19, coronaviruses, variants, flu infections, parasites, worms and anything else they patent to unleash on your or try to force on you. #hcq #hydroxychloroquine #ivermectin #covid-19 #vaccines

Hydroxychloroquine 3D molecular structure (Jmol) showing electrostatic potential surfaces. Firefly 8.2.0 PM3 energy minimum (no imaginary frequencies). Heat of formation = -29.41 kcal/mol. C-N-C=C torsion angle = 72.09 degrees. Legend: carbon atom: grey; hydrogen, white; nitrogen, blue; oxygen, red; chlorine, green. It is also known as Plaquenil (HCQ sulfate). C18H26ClN3O (freebase).

 

Although an early COVID-19 clinical trial using anti-malarial (±)-hydroxychloroquine (HCQ) was thought to show promise (especially when combined with azithromycin), more exhaustive global studies found no overall benefit.

www.news-medical.net/news/20220912/Mucosal-vaccination-tr...

 

Mucosal vaccination triggers superior T cell response against SARS-CoV-2 variants

 

In a recent study posted to the bioRxiv* server, researchers in Singapore and the United States demonstrated that intranasal (I.N.) delivery of a mucosal severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination triggered a superior T cell response compared to an equivalent dose of antigen delivered by the subcutaneous (S.C.) route. In addition, the I.N. vaccine-induced T cell phenotypes had polyfunctional interferon-gamma (IFN-γ) and tumor necrosis factor (TNF) expression and encompassed abundant T central memory (TCM) cells.

 

Background

 

The ongoing coronavirus disease 2019 (COVID-19) pandemic has necessitated unprecedented advances in vaccination technologies. However, the continuous emergence of new SARS-CoV-2 variants of concern (VOCs) poses a risk of frequent breakthrough infections and severe disease outcomes in multiple age groups, even in populations with high levels of vaccine coverage.

 

T cells are highly cross-reactive to multiple SARS-CoV-2 VOCs, SARS-CoV, and seasonal coronaviruses. Studies in non-human primates have pointed to a protective role of T cells in vaccine-induced protection. It is also noteworthy that SARS-CoV-2 infection begins at the mucosal surface of the nasal passages and lung airways. Therefore, there is an urgent need for alternative vaccine approaches for SARS-CoV-2, including subunit vaccines, which use adjuvants to promote immune activation.

 

Currently, there are no mucosal adjuvants approved for use in humans. Mastoparan-7 (M7), an analog of mastoparan, appears to work in vivo and has shown efficacy in enhancing the titer of antigen-specific antibodies in animal models when delivered via the S.C. route as well as application to the nasal mucosae. However, it is unknown if M7 influences T cell phenotypes and functions that are particularly important for combatting certain types of viral pathogens.

 

About the study

 

In the present study, researchers tested whether I.N. delivery of an adjuvanted subunit vaccine induced adequate SARS-CoV-2-specific T cell immune responses. They used eight to 10 weeks old C57BL/6 mice for all the vaccination experiments. The vaccine formulation comprised one μg of recombinant S-receptor-binding domain (RBD) protein with or without 20μg of M7.

 

They harvested spleens, popliteal LNs, or the nasal-associated lymphoid tissue (NALT), a rodent structure analogous to Waldeyer’s ring in humans, of all mice at necropsy on day 35 post-vaccination to prepare single-cell suspensions. They isolated red blood cells (RBCs) from the single-cell suspensions of the spleen and determined total cell numbers using a hemocytometer.

 

The team measured T cell responses five days post-vaccination by flow cytometry in the draining lymphoid organs for the respective tissues for S.C. or I.N. routes, respectively. They also assessed systemic T cell responses in the spleen following vaccination via both routes. Finally, the researchers visualized populations of T cells in the lymphoid organs using the UMAP algorithm, which they identified using the gating strategy.

 

Study findings

 

The currently used COVID-19 vaccines do not appear to induce robust airway-resident antigen-specific T cells, thus, necessitating the potential of next-generation COVID-19 vaccines to improve mucosal and systemic immune responses through modulation of T cells. Mucosal vaccination against the S-RBD antigen of SARS-CoV-2 promoted a T cell-intrinsic phenotype associated with superior systemic immune responses and antibody responses that improved antibody persistence in vivo and cross-protection against SARS-CoV-2 VOCs compared to S.C. vaccination with the same formulation.

 

The heightened systemic T cell responses in multiple T cell subsets in the spleen also persisted in the TMEM cell compartment for several weeks following the SARS-CoV-2 challenge. These TMEM cells exhibited an improved polyfunctional phenotype, characterized by dual expression of TNF and IFN-γ upon ex vivo stimulation and in vivo memory recall to antigen. An enhanced interleukin-17 (IL-17) production characterized the in vivo splenic T cell responses. Overall, the study results illustrated the polyfunctional nature of TMEM cells, independent of their peripheral tissue homing abilities. Indeed, T cells could help establish systemic mucosal vaccine-induced memory, of which TCM cells are a central component.

 

The increased numbers of L-selectin (CD62L)-expressing TCM cells within the TMEM compartment following mucosal vaccination is key for the homing of these cells to the spleen, which typified increased systemic immunity. During memory recall, TCM also likely served as a pool of T cells that replenished the TEM population.

 

The study results also pointed out that site-specific immune responses influence the long-term balance of T cell subpopulations. Therefore, during in vivo antigen challenge, the authors noted a marked increase in the numbers of CD8 TEM in the lung-draining brachial lymph nodes of recipients of I.N. route. Conversely, the ex vivo antigen restimulation of spleen T cells before adoptive transfer resulted in improved activation for CD8 TEM in S.C. vaccinated group.

 

Systemic T-cell responses also impact B cell-dependent antibody responses. Compared to S.C. vaccination, I.N. vaccination induced a relatively small but substantially higher level of neutralizing antibodies (nAbs) five weeks after the final vaccine boost and more nAbs with greater breadth against multiple SARS-CoV-2 VOCs. Most likely mucosal vaccination strategy preserved antibodies against more diverse epitopes within the polyclonal pool.

 

Conclusion

 

The current study is unique in using an M7 adjuvant, which could be injected into the skin and administered at mucosal surfaces, to directly compare the immune responses induced by the same dose of antigen administered via the two routes. The COVID-19 vaccines relying on high titer-specific nAbs with limited induction of mucosal responses need improvements. The mucosal vaccination strategy could prove helpful by helping improve the systemic immune responses and cross-reactive nAbs; thus, this strategy could potentially be used in the next-generation SARS-CoV-2 vaccines.

 

www.nature.com/articles/s42003-022-03841-8

 

Hydroxychloroquine blocks SARS-CoV-2 entry into the endocytic pathway in mammalian cell culture

 

Abstract

Hydroxychloroquine (HCQ), a drug used to treat lupus and malaria, was proposed as a treatment for SARS-coronavirus-2 (SARS-CoV-2) infection, albeit with controversy. In vitro, HCQ effectively inhibits viral entry, but its use in the clinic has been hampered by conflicting results. A better understanding of HCQ’s mechanism of actions in vitro is needed. Recently, anesthetics were shown to disrupt ordered clusters of monosialotetrahexosylganglioside1 (GM1) lipid. These same lipid clusters recruit the SARS-CoV-2 surface receptor angiotensin converting enzyme 2 (ACE2) to endocytic lipids, away from phosphatidylinositol 4,5 bisphosphate (PIP2) clusters. Here we employed super-resolution imaging of cultured mammalian cells (VeroE6, A549, H1793, and HEK293T) to show HCQ directly perturbs clustering of ACE2 receptor with both endocytic lipids and PIP2 clusters. In elevated (high) cholesterol, HCQ moves ACE2 nanoscopic distances away from endocytic lipids. In cells with resting (low) cholesterol, ACE2 primarily associates with PIP2 clusters, and HCQ moves ACE2 away from PIP2 clusters—erythromycin has a similar effect. We conclude HCQ inhibits viral entry through two distinct mechanisms in high and low tissue cholesterol and does so prior to inhibiting cathepsin-L. HCQ clinical trials and animal studies will need to account for tissue cholesterol levels when evaluating dosing and efficacy.

 

Introduction

Coronavirus disease 2019 (COVID-19), a viral infection caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), recently emerged as a serious public health problem. Currently, millions of people have been infected with SARS-CoV-2 worldwide. Proposed treatments for severe symptoms include a well-known FDA-approved antimalarial and anti-inflammatory agents chloroquine (CQ) and its derivative hydroxychloroquine (HCQ), but their mechanisms of action are poorly understood in human cells (and in particular in the presence of underlying conditions). A retrospective study claimed a benefit in particular with the macrolide antibiotic azithromycin. However, their use is not without controversy, and randomized control studies without an antibiotic appeared to have no benefit. In the treatment of malaria, CQ targets the replication cycle of the parasite; This mechanism of action is presumably unrelated to their actions in COVID-19, Lupus, and Niemann-Pick Syndrome. Understanding the underlying in vitro mechanism for these compounds in COVID-19 could help in understanding their mechanism of action in humans, in designing efficacious clinical trials, and in bettering the translation of their use in the clinic.

 

Previous research from the lab shows that a cholesterol-dependent mechanism for anesthetics regulates the movement of membrane proteins between monosialotetrahexosylganglioside1 (GM1) lipid clusters and PIP2 lipid clusters through perturbing the affinity of proteins for GM1 clusters. While the GM1 clusters are formed by cholesterol packing (Van der Waals interactions) with palmitates covalently attached to proteins (palmitoylation)15, the PIP2 clusters are formed from charged-protein clustering located near disordered lipids. We refer to the nonclustered region as the ‘disordered region’ of the cell since it is separate from GM1 clusters and contains unsaturated lipids that are disordered. PIP2 is thought to cluster near disordered lipids. In cellular membranes, both local and general anesthetics act as a chaotrope to disrupt the cholesterol-induced clustering of palmitoylated proteins. Within this process, cholesterol protects against the disruption of cells by sealing the air-water interface of the lipid membranes.

 

Cholesterol is critical to both viral entry and immune responses. The cholesterol-rich GM1 clusters facilitate endocytosis. SARS-CoV-2 surface receptor (angiotensinogen converting enzyme 2 (ACE2)) has recently been shown to move between GM1 clusters and PIP2 clusters in a cholesterol-dependent manner. As the cellular cholesterol level rises, both the number of endocytic lipids and their apparent cluster size increase. In an obese mouse model, cholesterol was high in lung tissue, and this correlated with ACE2 movement to the endocytic lipids, a condition that accelerated viral entry into the target cells in cell culture.

 

Cholesterol in blood appears to be low in multiple studies of COVID-19 patients with severe disease. However, the cellular cholesterol concentration measured in monocytes of the same patients was elevated, suggesting an opposite result in blood and tissue at the late stages of the disease. Importantly, cholesterol synthesis and uptake into immune cells is a key effector of inflammation. The cholesterol transport protein apolipoprotein E (apoE) both loads and unloads cholesterol to and from cellular membranes, allowing us to manipulate cholesterol levels both in vitro and in vivo.

 

Interestingly, CQ is an anesthetic—subcutaneous injections of CQ produce instant local anesthesia sufficient to perform a surgical procedure. Also, both CQ and tetracaine, a local anesthetic, are hydrophobic and contain a tertiary amine. Since CQ and local anesthetics (such as tetracaine) are weak bases, their uptake changes the acid-base balance within the membrane. Additionally, common local anesthetics (such as mepivacaine, bupivacaine, and tetracaine) and other GM1 cluster disrupting compounds (such as sterols and cyclodextrin) can exert antiviral or antimicrobial activity. Terpenoids can also disrupt viral entry; this process is cholesterol-dependent.

 

Both the cholesterol-dependent lipid disruption and antiviral properties of anesthetics, along with the anesthetic and antiviral properties of HCQ link the lipid disruption properties of HCQ with its viral-entry inhibiting effects. Further research into this link could help us understand both HCQ and anesthetics’ underlying molecular mechanism(s) in mammalian cells; in particular, mammalian cells in a high-cholesterol state—a state that is consistent with the chronic inflammation and the comorbidities of COVID-19, lupus, and Niemann pick. Prior models speculated that HCQ inhibited cathepsin-L by changing the endosomal pH. However, if HCQ disrupts ACE2 clustering, it would reverse the effects of cholesterol and inhibit the endocytic entry prior to the cathepsin-L cleavage. Here we use super-resolution imaging to show that HCQ disrupts the clustering of ACE2 with both endocytic lipids and PIP2.

 

Results

 

Inhibition of SARS-CoV-2 entry by anesthetic compounds

In order to test a membrane-disruptive mechanism for HCQ inhibition of SARS-CoV-2 viral entry, we compared HCQ to anesthetics (tetracaine and propofol) which are known to be membrane-disruptive. HEK293T cells overexpressing ACE2 were infected with a retrovirus pseudotyped with the SARS-CoV-2 spike protein (SARS2-PV). A segment of the spike protein binds to ACE2 and recapitulates viral entry. A luciferase encoded in the pseudotyped virus is then used to quantitate viral entry.

 

Treatments with HCQ, tetracaine, and propofol all robustly reduced SARS2-PV entry into HEK293T cells overexpressing ACE2. The cells were first treated with drugs (50 µM) for 1 h, then the drugs were removed. After the treatment and subsequent drug removal, SARS2-PV was applied such that the virus was never exposed to the drugs, thus avoiding potential direct effects of cholesterol on the viron. HCQ had the greatest effect on viral inhibition with almost a 90% reduction in SARS2-PV luciferase activity. We used 50 µM since that concentration was previously shown to be the minimum concentration that fully inhibited viral entry. The concentration is ~5-fold above the concentration found in lung epithelial lining fluid after 400 mg for 1 day making it an appropriate concentration to see a full effect by dSTORM. Like anesthetics, the actual concentration of HCQ in the membrane is dictated by a partition coefficient and the resultant mole fraction, not external concentration.

 

In Vero E6 cells, a cell line that endogenously expresses ACE2 receptor and robustly facilitates SARS-CoV-2 viral entry, HCQ, tetracaine, and propofol all significantly decreased viral entry. HCQ again showed the strongest effect decreasing viral entry by ~92%. Cell viability after HCQ treatment was assessed by Fixable Viability Dye (FVD) staining and MTT assay. The FVD staining labeled dead cells and found that HCQ treatment had no effect on Vero E6 cells, in agreement with a previous study, but did decrease live cell number by ~23.93 ± 5% in HEK293T cells. Similarly, the MTT assay showed HCQ treatment significantly decreased cell metabolism in HEK293T cells by ~36.05 ± 6%. However, the reduction in cell viability of HCQ did not account for the full reduction in viral entry. Tetracaine and propofol had no adverse effects on cell viability in vero E6 or HEK293T cells.

 

COVID-19 is often severe in obese patients and those with underlying conditions. We obtained lung samples from adult humans with chronic obstructive pulmonary disease (COPD). We found the lung tissue to have significantly higher free-cholesterol levels compared to cultured lung cell lines as measured by our fluorescent cholesterol assay. To recapitulate the physiological conditions observed in COVID-19 patients, we tested HCQ’s inhibition on viral entry in HEK293T loaded with cholesterol and overexpressing ACE2. To load cholesterol into cells, 4 µM apolipoprotein E (apoE, a cholesterol carrier protein linked to the severity of COVID-1951) was applied. ApoE binds to low-density lipoprotein (LDL) receptors in tissue and facilitates the loading of cholesterol into cells. To provide a source of cholesterol to the apoE, 10% fetal bovine serum (FBS, a common source of cholesterol) totaling ~310 µg/mL was added. Importantly, apoE is not present in FBS, allowing us to carefully control cholesterol loading. When apoE is in excess or in low-cholesterol conditions, it facilitates the efflux of cholesterol from the cell. Cells were treated acutely (1 h) for loading or unloading cholesterol prior to viral infection.

 

Loading cells with cholesterol into HEK293T cells overexpressing ACE2 increased viral entry by ~56 ± 38% l, which is consistent with observations with endogenously expressed ACE2 where cholesterol loading significantly increased viral entry by ~36 ± 7% (Supplementary Fig. 1g). As expected, treatment of cholesterol loaded cells with HCQ (~85 ± 12%) and tetracaine (~43 ± 12%) reduced SARS2-PV entry in a high-cholesterol state. The efficacy of HCQ was reduced in cholesterol loaded cells compared to non-cholesterol loaded cells, but only slightly.

 

To confirm that apoE loads and unloads cholesterol from cultured cells, we treated HEK293T, Vero E6, and A549 cells with apoE with and without 10% FBS and measured the relative change in membrane-free cholesterol. Cells that were incubated with and without a source of cholesterol contained small but significant increases and decreases in total cholesterol respectively. The loading and unloading of cholesterol were similar in H1793 cells, although the loading of cholesterol did not reach statistical significance.

 

HCQ’s disruption of ordered GM1 clusters

The ability of a virus to cluster is important for its infectivity and maturation. Previously, anesthetics were shown to perturb clustering in two ways. First, inhaled anesthetics tend to increase the apparent size and number of clusters, as observed using super-resolution imaging and cluster analysis, while local anesthetics tend to decrease the cluster size. Second, both inhaled and local anesthetics disassociate cholesterol-sensitive proteins from GM1 clusters. The dissociation of proteins from a GM1 cluster is recorded by two-color direct stochastic optical reconstruction microscopy (dSTORM) super-resolution imaging. The GM1 and PIP2 lipid, and ACE2 protein are fixed and labeled with cholera toxin B (CTxB, a pentadentate toxin binding GM1 lipids), PIP2 antibody, and ACE2 antibody, respectively, and then ACE2 association with the lipid is measured by pair correlation analysis. The antibodies in this study were previously validated for specificity (see methods). We previously used these techniques to monitor nanoscopic movement (<100 nm) of multiple proteins between both GM1 and PIP2 clusters.

 

(snip)

 

Reporting summary

Further information on research design is available in the

Nature Research Reporting Summary linked to this article.

Toronto, Canada. Hydroxychloroquine, prescription for Lupus or Rheumatoid Arthritis, being pushed by Donald Trump as a possible drug to combat #Covid19, with no evidence © Linda Dawn Hammond/ IndyFoto April 19, 2020.

 

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