View allAll Photos Tagged retesting
I began designing this model in November of 2018, and I'm proud to announce that, finally, after months of building and rebuilding, testing and retesting, my Southern #1401 replica is complete and in flawless operating condition!
A big thanks to Andrew Mollmann of OKBrickWorks for the livening decals, and to Cameron Miller, Glenn Holland and Cale Leiphart for suggestions, tips and tricks.
Please enjoy the complete album on my personal Flickr page and be sure to like/comment!
I began designing this model in November of 2018, and I'm proud to announce that, finally, after months of building and rebuilding, testing and retesting, my Southern #1401 replica is complete and in flawless operating condition!
A big thanks to Andrew Mollmann of OKBrickWorks for the livening decals, and to Cameron Miller, Glenn Holland and Cale Leiphart for suggestions, tips and tricks.
Please enjoy the complete album on my personal Flickr page and be sure to like/comment!
Just retesting the spot before a whole run of post-Christmas rail replacement…
On a cloudy and mildly chilly morning, Stephensons of Essex ADL Enviro200 YX17NYW (428) heads along Station Road in Elsenham whilst working a Route 7A service towards Bishops Stortford 16/12/25
I actually didn't mind the styling of the Xsara coupe, but those steel wheels and trims do it no favours in my opinion; a set of alloys would set it off lovely. Showing 108k as of last MOT a year; it's due a retest in a couple of weeks. Current owner since Jan 09; a good run.
Oi gente!!
Quando peguei esse indie, testei sobre vários esmaltes de cores diferentes, porém, sempre algum glitter "passava despercebido" por ser muito similar à cor de base, então escolhi usá-lo sobre um nude. Peguei um nude qlqr da caixa de não usados e esmaltei, porém, depois de tudo pronto achei que não destacou mto a esmaltação... Não tive ânimo pra retestar outras cores e reesmaltar tudo, mas tenho certeza que numa próxima vez farei isso.
De qualquer forma, acho que dá pra ver bem os glitters na foto e dá pra ver que esse indie é lindoo!! As cores predominantes são rosa, lilás e verde. Ele foi o glitter feito exclusivamente para a Maria Gastadeira e quem comprou tenho certeza que não vai se arrepender!
Eu estou viciada nos indies, tenho que tentar usar mais esmaltes "normais", pois a caixinha de não usados é grande!!
Ótimo final de semana!! Bjos!
Anglia Car Auctions, King's Lynn -
"Supplied new in Australia. Recently imported to the UK although registration required. The MoT failure sheet dated 9th June 2017 advises that the brakes require adjustment before it's retest. Comes with Australian registration documents and NOVA reference. 1,911cc. 48,399 kilometres. Chassis number 3407309.
Estimate: £17,000 - 22,000."
Unsold.
I began designing this model in November of 2018, and I'm proud to announce that, finally, after months of building and rebuilding, testing and retesting, my Southern #1401 replica is complete and in flawless operating condition!
A big thanks to Andrew Mollmann of OKBrickWorks for the livening decals, and to Cameron Miller, Glenn Holland and Cale Leiphart for suggestions, tips and tricks.
Please enjoy the complete album on my personal Flickr page and be sure to like/comment!
I began designing this model in November of 2018, and I'm proud to announce that, finally, after months of building and rebuilding, testing and retesting, my Southern #1401 replica is complete and in flawless operating condition!
A big thanks to Andrew Mollmann of OKBrickWorks for the livening decals, and to Cameron Miller, Glenn Holland and Cale Leiphart for suggestions, tips and tricks.
Please enjoy the complete album on my personal Flickr page and be sure to like/comment!
I began designing this model in November of 2018, and I'm proud to announce that, finally, after months of building and rebuilding, testing and retesting, my Southern #1401 replica is complete and in flawless operating condition!
A big thanks to Andrew Mollmann of OKBrickWorks for the livening decals, and to Cameron Miller, Glenn Holland and Cale Leiphart for suggestions, tips and tricks.
Please enjoy the complete album on my personal Flickr page and be sure to like/comment!
It's hard to believe the Z3 is knocking on 20 years old now. The same basic silohouette is used on the new Z4 and even now, the Z3 still looks modern and timeless. BMW design in the mid 90s was very special indeed with this being one of the highlights in my opinion.
It's also quite rare to see a red one with the hard top; usually I'd say the Z3 suits dark colours better but I really like this. It's been in current hands now since the beginning of October 2000 and by the looks of it has been looked after meticulously. There hasn't been one single MOT advisory since records began and the mileage was showing a tiny 39k when it was last tested a year ago (it's due a retest next week). This car will be worth a serious fortune in years to come if it is kept like this.
I began designing this model in November of 2018, and I'm proud to announce that, finally, after months of building and rebuilding, testing and retesting, my Southern #1401 replica is complete and in flawless operating condition!
A big thanks to Andrew Mollmann of OKBrickWorks for the livening decals, and to Cameron Miller, Glenn Holland and Cale Leiphart for suggestions, tips and tricks.
Please enjoy the complete album on my personal Flickr page and be sure to like/comment!
I began designing this model in November of 2018, and I'm proud to announce that, finally, after months of building and rebuilding, testing and retesting, my Southern #1401 replica is complete and in flawless operating condition!
A big thanks to Andrew Mollmann of OKBrickWorks for the livening decals, and to Cameron Miller, Glenn Holland and Cale Leiphart for suggestions, tips and tricks.
Please enjoy the complete album on my personal Flickr page and be sure to like/comment!
On the left, Valrhona cocoa. On the right, Hershey's. Such a huge difference! But not what I was testing, of course.
Tried the Kalamazoo Stout to go with the burger they tout as special, made from a blend of 3 cuts. However I wasn't so impressed, maybe it was the late hour; have to retest.
Hmm, this is just the first image but it seems like an additional step I added on my film developing and scanning workflow has significantly increased the quality of my images. Well, I still have to practice composition but that's another story!
Suddenly I am satisfied with the level of detail and sharpness of the scans. It doesn't look like they were taken with a toy camera anymore. It seem like I have to rescan ALL of my negatives if this is confirmed.
----
Olympus Stylus Epic DLX (point and shoot)
Fujifilm 200
Self Dev Unicolor C-41 (almost 20 films developed so far with this chem)
Extra secret step until I can confirm it. lol
Epson V600 scan / Lightroom
Original Caption: Woman Watches as Minor Adjustments Were Made to Her Auto's Carburetor During Retesting after Her Vehicle Had Failed at an Auto Emission Inspection Station in Downtown Cincinnati, Ohio. It Turned Out That It Was a Major Carburetor Problem, and She Was Given a 30-Day Temporary Sticker to Have It Corrected. Since January, 1975, All Light Duty, Spark Ignition Powered Motor Vehicles Must Be Tested Annually for Carbon Monoxide and Hydrocarbon Emissions. 09/1975
U.S. National Archives’ Local Identifier: 412-DA-15466
Photographer: Eiler, Lyntha Scott, 1946-
Subjects:
Cincinnati (Hamilton county, Ohio, United States) inhabited place
Environmental Protection Agency
Project DOCUMERICA
Persistent URL: arcweb.archives.gov/arc/action/ExternalIdSearch?id=557916
Repository: Still Picture Records Section, Special Media Archives Services Division (NWCS-S), National Archives at College Park, 8601 Adelphi Road, College Park, MD, 20740-6001.
For information about ordering reproductions of photographs held by the Still Picture Unit, visit: www.archives.gov/research/order/still-pictures.html
Reproductions may be ordered via an independent vendor. NARA maintains a list of vendors at www.archives.gov/research/order/vendors-photos-maps-dc.html
Access Restrictions: Unrestricted
Use Restrictions: Unrestricted
Depuis deu xjours je travail à ça... des shoes ! c'est pas un secret c'est mon petit vice, mon obsession dollesque... du coup la taille MNF me permet d'assouvir cette obsession de créer de toute pièces mes shoes pour doll...
Bon là c'est ma première paires, c'est pas parfait mais c'est tout à fait portable :)
le patron est donc aprouvé y'a plus qu'a retester et décliner !
Plants behave in some oddly intelligent ways: fighting predators, maximizing food opportunities ... But can we think of them as actually having a form of intelligence of their own?
Are plants intelligent? Can they solve problems, communicate, and navigate their surroundings? For centuries, philosophers and scientists have argued that plants are unthinking and inert – yet discoveries over the past 50 years have challenged this idea, shedding new light on the complex interior lives of plants.Are plants intelligent? Can they solve problems, communicate, and navigate their surroundings? Or are they passive, incapable of independent action or social behavior? Philosophers and scientists have pondered these questions since ancient Greece, most often concluding that plants are unthinking and inert: they are too silent, too sedentary -- just too different from us. Yet discoveries over the past fifty years have challenged these ideas, shedding new light on the extraordinary capabilities and complex interior lives of plants.
In Brilliant Green, Stefano Mancuso, a leading scientist and founder of the field of plant neurobiology, presents a new paradigm in our understanding of the vegetal world. Combining a historical perspective with the latest in plant science, Mancuso argues that, due to cultural prejudices and human arrogance, we continue to underestimate plants. In fact, they process information, sleep, remember, and signal to one another -- showing that, far from passive machines, plants are intelligent and aware. Through a survey of plant capabilities from sight and touch to communication, Mancuso challenges our notion of intelligence, presenting a vision of plant life that is more sophisticated than most imagine.
Plants have much to teach us, from network building to innovations in robotics and man-made materials -- but only if we understand more about how they live. Part botany lesson, part manifesto, Brilliant Green is an engaging and passionate examination of the inner workings of the plant kingdom.
In Brilliant Green, leading scientist Stefano Mancuso presents a new paradigm in our understanding of the vegetal world. He argues that plants process information, sleep, remember, and signal to one another – showing that, far from passive machines, plants are intelligent and aware. Part botany lesson, part manifesto, Brilliant Green is an engaging and passionate examination of the inner workings of the plant kingdom.
www.ted.com/talks/stefano_mancuso_the_roots_of_plant_inte...
The Botany of Desire: A Plant's-Eye View of the World is a 2001 nonfiction book by journalist Michael Pollan. Pollan presents case studies that mirror four types of human desires that are reflected in the way that we selectively grow, breed, and genetically engineer our plants. The tulip beauty, marijuana intoxication, the apple sweetness and the potato control.
en.wikipedia.org/wiki/The_Botany_of_Desire
Are plants intelligent? Can they solve problems, communicate, and navigate their surroundings? Or are they passive, incapable of independent action or social behavior? Philosophers and scientists have pondered these questions since ancient Greece, most often concluding that plants are unthinking and inert: they are too silent, too sedentary -- just too different from us. Yet discoveries over the past fifty years have challenged these ideas, shedding new light on the extraordinary capabilities and complex interior lives of plants.
In Brilliant Green, Stefano Mancuso, a leading scientist and founder of the field of plant neurobiology, presents a new paradigm in our understanding of the vegetal world. Combining a historical perspective with the latest in plant science, Mancuso argues that, due to cultural prejudices and human arrogance, we continue to underestimate plants. In fact, they process information, sleep, remember, and signal to one another -- showing that, far from passive machines, plants are intelligent and aware. Through a survey of plant capabilities from sight and touch to communication, Mancuso challenges our notion of intelligence, presenting a vision of plant life that is more sophisticated than most imagine.
Plants have much to teach us, from network building to innovations in robotics and man-made materials -- but only if we understand more about how they live. Part botany lesson, part manifesto, Brilliant Green is an engaging and passionate examination of the inner workings of the plant kingdom.
Financial support for the translation of this book has been provided by SEPS: Segretariato Europeo Per Le Pubblicazioni Scientifiche. - See more at: islandpress.org/book/brilliant-green#sthash.ThqSqcvm.dpuf
The stories range from the true story of Johnny Appleseed to Pollan's first-hand research with sophisticated marijuana hybrids in Amsterdam to the paradigm-shifting possibilities of genetically engineered potatoes. Pollan also discusses the limitations of monoculture agriculture: specifically, the adoption in Ireland of a single breed of potato (the Lumper) made the Irish vulnerable to a fungus to which it had no resistance, resulting in the Irish Potato Famine. The Peruvians from whom the Irish had gotten the potato grew hundreds of varieties, so their exposure to any given pest was slight.
Flowers can also be used to convey a message, and to share our feelings. Flowers, similar to colours are often used to convey a message, or to deliver a warning to us.Flowers and plant life have a wide range of uses from sustenance, to medicine, to gestures of affection and almost everything in between.Plant life converts carbon monoxide to oxygen, and without plants, we could not exist in our present human form.As well as traditional and modern medicines, essences and oils extracted from plant life are used for aroma therapy healing practices and the like.Plants extracts and essences are used in many Wiccan rituals.These uses of plants are valid and essential but, they are only the beginning of our understanding of the nature of plant life.
Cosmic Energy Renewal
Mostly, we attempt to obtain cosmic energy from others, either through conflict wherein we take another's cosmic energy, or through providing assistance to others who give us their cosmic energy.Cosmic energy obtained from others is short lived, and unless we can link with a partner, or a series of partners who we can dominate and draw cosmic energy from permanently, we are soon looking for another opportunity to obtain cosmic energy from others.There are many natural sources of cosmic energy which we can, and do draw upon, often unaware that we do so. We do not need to obtain energy from others, and when we discontinue seeking to obtain energy from others, we lose any desire for conflict, in any guise.One excellent and readily available source of cosmic energy is plant life. Being attached to the earth, plants draw cosmic energy directly from the earth. We are able to draw cosmic energy from plant life, which is why we will often return from spending time in a garden feeling renewed and 'up'.When we draw cosmic energy from plant life, we are assisting the plant life to renew their cosmic energy so that instead of a relatively stagnant amount of cosmic energy residing with the plant, a constant stream of renewed energy passes through the plant. This is why some people seem to have a 'green thumb', they draw energy through the plant life in their gardens.
Fairies.
Fairies have long been the subject of fantasy and debate. Fairies have been photographed and investigated, and fairies have been discounted by sceptics.Fairies have been said to have special powers, and to inhabit realms such as 'middle earth'. Fairies have been seen in dreams and reality. Fairies have been witnessed by children and adults, both intoxicated and sober.The key to understanding the truth of the existence of fairies is to consider the common denominator which is prevalent in most tales of fairies, which is the connection between fairies and plant life.There are many who know that fairies reside 'at the bottom of their garden'. Fairies do reside at the bottom of gardens, every garden.Just as we, and every living thing has a physical body and a spirit body, so too do plants. The spirit bodies of those in human form have been witnessed on astral travels, and have been labelled when unattached to a physical body as ghosts or spirits. The spirit bodies of plant life have been witnessed on many occasions, sometimes with acceptance, and other times with disbelief. The spirit bodies of plant life, have been labelled Fairies.Fairies are no different to any other spirits. Fairies exist on the spirit plane, and fairies are occasionally witnessed, more often than we realise, by those of us in a physical existence.
The Meaning Of Flowers.
Flowers can also be used to convey a message, and to share our feelings. Flowers, similar to colours are often used to convey a message, or to deliver a warning to us.We can receive a message in this way either when we encounter a flower on the physical plane, or when we encounter a flower on the spirit plane, in our 'dreams'.If we encounter a broken flower, the meaning of the flower will usually be reversed.
www.eaglespiritministry.com/works/flower.htm
The intelligent Plant. That is the title of a recent article in The New Yorker — and new research is showing that plants have astounding abilities to sense and react to the world.The Intelligent Plant. That is the title of a recent article in The New Yorker — and new research is showing that plants have astounding abilities to sense and react to the world.
This story is based on a radio interview. Listen to the full interview.But can a plant be intelligent? Some plant scientists insist they are — since they can sense, learn, remember and even react in ways that would be familiar to humans.Michael Pollan, author of such books as "The Omnivore's Dilemma" and "The Botany of Desire," wrote the New Yorker piece about the developments in plant science. He says for the longest time, even mentioning the idea that plants could be intelligent was a quick way to being labeled "a whacko." But no more, which might be comforting to people who have long talked to their plants or played music for them.The new research, he says, is in a field called plant neurobiology — which is something of a misnomer, because even scientists in the field don't argue that plants have neurons or brains."They have analagous structures," Pollan explains. "They have ways of taking all the sensory data they gather in their everyday lives ... integrate it and then behave in an appropriate way in response. And they do this without brains, which, in a way, is what's incredible about it, because we automatically assume you need a brain to process information."And we assume you need ears to hear. But researchers, says Pollan, have played a recording of a caterpillar munching on a leaf to plants — and the plants react. They begin to secrete defensive chemicals — even though the plant isn't really threatened, Pollan says. "It is somehow hearing what is, to it, a terrifying sound of a caterpillar munching on its leaves."
Pollan says plants have all the same senses as humans, and then some. In addition to hearing, taste, for example, they can sense gravity, the presence of water, or even feel that an obstruction is in the way of its roots, before coming into contact with it. Plant roots will shift direction, he says, to avoid obstacles.So what about pain? Do plants feel? Pollan says they do respond to anesthetics. "You can put a plant out with a human anesthetic. ... And not only that, plants produce their own compounds that are anesthetic to us." But scientists are reluctant to go as far as to say they are responding to pain.How plants sense and react is still somewhat unknown. They don't have nerve cells like humans, but they do have a system for sending electrical signals and even produce neurotransmitters, like dopamine, serotonin and other chemicals the human brain uses to send signals."We don't know why they have them, whether this was just conserved through evolution or if it performs some sort of information processing function. We don't know. There's a lot we don't know," Pollan says.And chalk up another human-like ability — memory. Pollan describes an experiment done by animal biologist Monica Gagliano. She presented research that suggests the mimosa pudica plant can learn from experience. And, Pollan says, merely suggesting a plant could learn was so controversial that her paper was rejected by 10 scientific journals before it was finally published.Mimosa is a plant, which looks something like a fern, that collapses its leaves temporarily when it is disturbed. So Gagliano set up a contraption that would drop the mimosa plant, without hurting it. When the plant dropped, as expected, its leaves collapsed. She kept dropping the plants every five to six seconds."After five or six drops, the plants would stop responding, as if they'd learned to tune out the stimulus as irrelevent," Pollan says. "This is a very important part of learning — to learn what you can safely ignore in your environment."Maybe the plant was just getting worn out from all the dropping? To test that, Gagliano took the plants that had stopped responding to the drops and shook them instead. "They would continue to collapse," Pollan says. "They had made the distinction that [dropping] was a signal they could safely ignore. And what was more incredible is that [Gagliano] would retest them every week for four weeks and, for a month, they continued to remember their lesson."That's as far out as Gagliano tested. It's possible they remember even longer. Conversely, Pollan points out, bees that are given a similar dishabituation test forget what they've learned in as little as 48 hours.Pollan says not everyone accepts that what Gagliano describes is really learning. In fact, there are many critics with many alternative theories for explaining the response the plants are having. Still ..."Plants can do incredible things. They do seem to remember stresses and events, like that experiment. They do have the ability to respond to 15 to 20 environmental variables," Pollan says. "The issue is, is it right to call it learning? Is that the right word? Is it right to call it intelligence? Is it right, even, to call what they are conscious. Some of these plant neurobiologists believe that plants are conscious — not self-conscious, but conscious in the sense they know where they are in space ... and react appropriately to their position in space."Pollan says there is no agreed definition of intelligence. "Go to Wikipedia and look up intelligence. They despair of giving you an answer. They basically have a chart where they give you nine different definitions. And about half of them depend on a brain — they refer to abstract reasoning or judgment."And the other half merely refer to a problem-solving ability. And that's the kind of intelligence we are talking about here.... So intelligence may well be a property of life. And our difference from these other creatures may be a matter of difference of degree rather than kind. We may just have more of this problem-solving ability and we may do it in different ways."Pollan says that really freaks people out — "that the line between plants and animals might be a little softer than we traditionally think of it as."And he suggests that plants may be able to teach humans a thing or two, such as how to process information without a central command post like a brain.
Check out this video of Michael Pollan discussing time-lapse photography of bean plants looking very purposeful.
www.pri.org/stories/2014-01-09/new-research-plant-intelli...
so I grew up I am? For ten years, a lively debate on the intelligence of plants animates the community of biologists of the plant world. Heresy, shout some, truth, say others.
At the head of the latter, Stefano Mancuso, founder of the International Plant Neurobiology Laboratory, confirmed and signed in his latest book, Brilliant Green (Michael Pollan, 2015, not translated): "The most recent studies of the plant world have shown that plants are sensitive (and therefore are endowed with sense), they communicate (with each other and with animals), sleep, remember and can even manipulate other species. They can be described as intelligent. "Among researchers interviewed on the subject, the discomfort is systematic. Already in 2008, Thirty-six European and North American biologists signed a manifesto published in Trends in Plant Science, led by the Italian Amedeo Alpi (University of Pisa), to denounce the use of "Neurobiology" which under -entendrait intelligence of plants.
It must be said that trauma has long shaken plant biologists. In 1973 the release of the book The Secret Life of Plants by Peter Tomkins and Christopher Bird (The Secret Life of Plants, Robert Laffont ,.
www.lemonde.fr/sciences/article/2016/02/29/un-vif-debat-s...
I began designing this model in November of 2018, and I'm proud to announce that, finally, after months of building and rebuilding, testing and retesting, my Southern #1401 replica is complete and in flawless operating condition!
A big thanks to Andrew Mollmann of OKBrickWorks for the livening decals, and to Cameron Miller, Glenn Holland and Cale Leiphart for suggestions, tips and tricks.
Please enjoy the complete album on my personal Flickr page and be sure to like/comment!
Depuis deu xjours je travail à ça... des shoes ! c'est pas un secret c'est mon petit vice, mon obsession dollesque... du coup la taille MNF me permet d'assouvir cette obsession de créer de toute pièces mes shoes pour doll...
Bon là c'est ma première paires, c'est pas parfait mais c'est tout à fait portable :)
le patron est donc aprouvé y'a plus qu'a retester et décliner !
First of all a very big thanks to all the guys over at FM for all the great information regarding adding a front end filter to the ZM 35mm Distagon to help cure corner smearing caused by the sensor cover glass plate / Field curvature....Brilliant combined work on everybody's behalf :-)
My Opto Sigma correction glass (SLB-50-5000PM) eventually turned up the other day for my ZM 35mm Distagon...I tried a bunch of step up and step down filter rings to find what worked the best to house the glass, whilst checking continuously for any signs of vignetting.
A 49mm step up to 55mm > then a 55mm step down to 52mm > then the Opto Sigma glass held in place with a 52mm retention ring taken from a cheap 52mm UV filter > then a 52mm step up to 58mm filter ring which acts as a shallow hood and also allows a lens cap now to be easily attached ...This worked the best for me....I used a rubber O ring to centre the OS glass within the filter itself, this was awkward to fit and took me several hours! I opted for the convex side of the Opto Sigma glass to be facing in towards the camera rather than outwards.
I tested this with and without the filter above attached at various apertures...The difference was like night and day....The filter is DEFINITELY the way to go if you want improved corners with the ZM.
The downside is that with the OS glass attached it wouldn't allow the lens to focus all the way to infinity - I tested this with my 4 Leica M to E mount adapters (Novoflex, Yeenon close-up, Voigtlander close-up and a cheap knock off pseudo Hawkes close-up adapter) none of these allowed the lens to focus to infinity.
I therefore had to unscrew the 4 screws on the Leica M mount to get at the shims (This might possibly void the Zeiss warranty as screws are loctited in place).
With the rear M mount now removed I had 4 shims just behind the M mount ZM lens.
2 x thick gold shims
1 x medium silver shim
1 x thin bronze shim
(Note I had different shims inside my lens as opposed to what Bastian K had inside his ZM 35mm Distagon).
I tried various combinations by removing different shims one at a time and reassembling the lens and retesting @ F1.4 for infinity over and over again...on the 4th attempt success! I found that just removing 1 gold shim with my version of this lens, it now focused as near to infinity as you could possibly hope for.
I then retested for vignetting and DoF tests at various apertures and all works great :-)...The Zeiss hood will not fit this particular set up BTW...(Note to Teera...Sadly I couldn't find anybody here in Cornwall prepared to grind this 50mm diameter OS glass to fit a 49mm filter ring).
IMO the Zeiss ZM 35mm Distagon is now equal and may possibly be a tad better IQ wise than my Sony 35mm FE Distagon...before the conversion was carried out I thought that my Sony had better IQ for stopped down landscape work...
The Zeiss ZM has better cooler more neutral colours than the warmer Sony FE lens.
I feel the ZM is a true 35mm FL lens (Before conversion) and the Sony is very slightly wider angled.
The ZM 35mm Distagon (including OS glass filter rings and front and rear caps shown) Vs. Sony 35mm Distagon (including B+W thin clear filter, hood and front and rear caps shown) I measured to be 174g lighter in favour of the ZM.
The ZM is much smaller and has a lovely solid feel to it...Manual focusing is buttery smooth and a joy to use.
Both lenses have a superb wide open OoF rendering.
The Sony has less vignetting and provides exif data information unlike the ZM lens does.
Bottom line in terms of IQ - If you don't want to go through all the hassle of the conversion above (i.e. making up a filter and shim removal) then go with the Sony AF and save yourself a load of money and aggro.
If you can be bothered carrying out the conversion above then I think you won't regret going via the ZM route, especially if you prefer manual focus lenses.
I hope that helps anybody interested in getting either of these two great lenses.
Please don't ask which I prefer the best, as I like them both equally and will keep them both.
Cheers Barry
This parked right outside my work today, so seemed rude not to get a photo.
It failed it's MOT in June on possibly the longest list of corrosion-related issues I've ever seen, but was presented for a retest 10 days later.
This is not the first Talbot Express Camper called 'Camelot' that I've seen. I knew of one for many years near my aunt and uncles house, unless this is the same one.
There must be an interesting story behind this as it was last taxed in 1985 when just two years old and has done a mere 7000 miles. It has never had an MoT; it failed one a couple of weeks ago on brakes and lights and judging by the bird poo on the windscreen has been parked here since awaiting repair and retest. There are very few 505s left in the UK thanks to a thriving export trade and none of the STI model are currently taxed.
Original Caption: Car Enters the Safety Lane at the Norwood, Ohio, Auto Emission Inspection Station. Located in a Residential Area a Block Away From Main Street, the Building Was an Open Air Market in the 1920's. All Light Duty, Spark Ignition Powered Motor Vehicles in Norwood Must Be Certified Annually. If a Vehicle Fails the Test for Carbon Monoxide and Hydrocarbon Emissions, the Owner Is Given a 30-Day Temporary Sticker to Allow Time for Repairs and Retesting 08/1975
U.S. National Archives’ Local Identifier: 412-DA-15389
Photographer: Eiler, Lyntha Scott, 1946-
Subjects:
Norwood (Hamilton county, Ohio, United States) inhabited place
Environmental Protection Agency
Project DOCUMERICA
Persistent URL: arcweb.archives.gov/arc/action/ExternalIdSearch?id=557839
Repository: Still Picture Records Section, Special Media Archives Services Division (NWCS-S), National Archives at College Park, 8601 Adelphi Road, College Park, MD, 20740-6001.
For information about ordering reproductions of photographs held by the Still Picture Unit, visit: www.archives.gov/research/order/still-pictures.html
Reproductions may be ordered via an independent vendor. NARA maintains a list of vendors at www.archives.gov/research/order/vendors-photos-maps-dc.html
Access Restrictions: Unrestricted
Use Restrictions: Unrestricted
I had time today to retest this, see the video below. I step through most of the Picture Profiles on the Sony a7rii including sgamut which should have a larger gamut and perhaps prevent the bending (but I didn't see it helping).
The Picture Profile 3 where I stopped talking is Andrew Reid's EOSHD Sony Pro Color settings.
My guess is Sony cameras like the a7rii just have a hard time staying withing the color gamut for the red channel (even with sgamut). Somehow Canon seems to have this figured how when it comes to car tail lights.
Original Caption: Woman, Center, Is Having Minor Adjustments Made to Her Auto's Carburetor During Retesting after Her Vehicle Had Failed at an Auto Emission Inspection Station in Downtown Cincinnati, Ohio All Light Duty, Spark Ignition Powered Motor Vehicles Must Be Tested Annually for Carbon Monoxide and Hydrocarbon Emissions Since January, 1975. They Also Must Have a Safety Check Which Has Been in Effect Since 1940. 09/1975
U.S. National Archives’ Local Identifier: 412-DA-15465
Photographer: Eiler, Lyntha Scott, 1946-
Subjects:
Cincinnati (Hamilton county, Ohio, United States) inhabited place
Environmental Protection Agency
Project DOCUMERICA
Persistent URL: arcweb.archives.gov/arc/action/ExternalIdSearch?id=557915
Repository: Still Picture Records Section, Special Media Archives Services Division (NWCS-S), National Archives at College Park, 8601 Adelphi Road, College Park, MD, 20740-6001.
For information about ordering reproductions of photographs held by the Still Picture Unit, visit: www.archives.gov/research/order/still-pictures.html
Reproductions may be ordered via an independent vendor. NARA maintains a list of vendors at www.archives.gov/research/order/vendors-photos-maps-dc.html
Access Restrictions: Unrestricted
Use Restrictions: Unrestricted
No blood transfusion! Platelets are up. We retest on Monday. Have a great weekend. Im sure he will!.
Quite a nice colour for one of these; this one looks a tidy example and rare with the more powerful 103bhp engine.
It's been in current hands since August 2004 when it was three months old; it was on about 62k last May when it was MOT'd, it's due a retest in a couple of weeks.
Anglia Car Auctions, King's Lynn -
"Supplied new in Australia. Recently imported to the UK although registration required. The MoT failure sheet dated 9th June 2017 advises that the brakes require adjustment before it's retest. Comes with Australian registration documents and NOVA reference. 1,911cc. 48,399 kilometres. Chassis number 3407309.
Estimate: £17,000 - 22,000."
Unsold.
Original Caption: Young Girl on a Visit to Her Grandmother in Norwood, Ohio the Home Is near an Auto Emission Inspection Station Where All Light Duty, Spark Ignition Powered Vehicles Registered in the City Must Be Certified Annually for Carbon Monoxide and Hydrocarbon Emissions. If a Vehicle Fails the Test, the Owner Is Given a 30-Day Temporary Sticker to Allow Him Time for Repairs and Retesting 08/1975
U.S. National Archives’ Local Identifier: 412-DA-15393
Photographer: Eiler, Lyntha Scott, 1946-
Subjects:
Norwood (Hamilton county, Ohio, United States) inhabited place
Environmental Protection Agency
Project DOCUMERICA
Persistent URL: arcweb.archives.gov/arc/action/ExternalIdSearch?id=557843
Repository: Still Picture Records Section, Special Media Archives Services Division (NWCS-S), National Archives at College Park, 8601 Adelphi Road, College Park, MD, 20740-6001.
For information about ordering reproductions of photographs held by the Still Picture Unit, visit: www.archives.gov/research/order/still-pictures.html
Reproductions may be ordered via an independent vendor. NARA maintains a list of vendors at www.archives.gov/research/order/vendors-photos-maps-dc.html
Access Restrictions: Unrestricted
Use Restrictions: Unrestricted
It was touch and go whether the Base would make it to Shitefest, having failed its MoT shortly before. Following an epic week of heroic welding by its current custodian, it was presented for a retest on Friday morning and with a fresh ticket successfully gained it was straight on its way to the event. Things were so tight there wasn't even time to rub down and paint the repaired wheelarch so it's now looking even scruffier, and still wears the odd Fiesta wheel with pride.
Original Caption: Car Enters the Safety Lane at the Norwood, Ohio Auto Emission Inspection Station. Located in a Residential Area a Block Away From Main Street, the Building Was an Open Air Market in the 1920's. All Light Duty, Spark Ignition Powered Motor Vehicles in the City Must Be Certified Annually. If a Vehicle Fails the Test for Carbon Monoxide and Hydrocarbon Emissions, the Owner Is Given a 30-Day Temporary Sticker to Allow Time for Repairs and Retesting 09/1975
U.S. National Archives’ Local Identifier: 412-DA-15390
Photographer: Eiler, Lyntha Scott, 1946-
Subjects:
Norwood (Hamilton county, Ohio, United States) inhabited place
Environmental Protection Agency
Project DOCUMERICA
Persistent URL: arcweb.archives.gov/arc/action/ExternalIdSearch?id=557840
Repository: Still Picture Records Section, Special Media Archives Services Division (NWCS-S), National Archives at College Park, 8601 Adelphi Road, College Park, MD, 20740-6001.
For information about ordering reproductions of photographs held by the Still Picture Unit, visit: www.archives.gov/research/order/still-pictures.html
Reproductions may be ordered via an independent vendor. NARA maintains a list of vendors at www.archives.gov/research/order/vendors-photos-maps-dc.html
Access Restrictions: Unrestricted
Use Restrictions: Unrestricted
A respot from 2014; it's good to see this still going and looking better now than it did back then. Last MOT'd a year ago (it's due a retest next week) showing 86k, but that could be kilometres.
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
so im probably pretty obsessed currently with some facebook apps called: KaChing (virtual stock market), Farm Town, Farmville and Barn Buddy, oh and bejeweled blitz. i really should be studying for my life insurance retest. i got it rescheduled again for this Friday at 1pm, I'll be paying classes and ordering books tomorrow morning. i'm off so that would be a relief.
still struggling financially regarding my furkids vet bills. oh and i owe my mom 480 for my photography class.... wooooo... (sigh). BUT BUT BUT i am saving some money and all the money that im spending on my licensing is going to be worth it later on.
a speedlite is going to have to wait. :(
p.s. i like high key shots so much better than low key, but i figured i'd give it a shot.
if you want to be facebook buddies, send me a flickrmail of your email address for facebook. its so much more easier for me to find you then for you to find me, im impossible to find unless you are a friend of a friend. :)
TRP: Black Background
Tim Armstrong, CEO of AOL, is interviewed on-stage as part of the company's presentation about content and online strategy during Advertising Week. Taken on September 29, 2010 in The Times Center.
Update: Featured in this Japanese blog post about the art of listening vs speaking in the business world kazumoto.jp/?p=1501
And in this blog post about interviewing techniques wisewolftalking.com/2011/11/24/856/
And in this Spanish language blog post about recruiting and the interview process www.unemprendedor.com/ser-emprendedor/325-seleccion-de-pe...
Used in this blog post about IT strategy and talent recruiting www.orsyp.com/blog/684-what-are-the-top-7-it-strategies-y...
As seen in this blog post about job interviews laugh-raku.com/archives/4560
Featured in this Chinese blog post about interview skills blog.alphacamp.co/2014/12/31/startup-ux-3/
Used in this blog post about behavioral interview techniques leavingthepublicsector.net/2011/11/24/856/
Created as a flash card image here quizlet.com/20576851/collocations-with-go-take-get-and-do...
Featured in this Romanian blog post about non-verbal signals sent by managers during the job interview process www.managerexpress.ro/company/hr/comportamentul-nonverbal...
Used in this blog post about hiring employees abroad clickhowto.com/how-to-employ-staff-in-a-foreign-country/
Part of a lesson plan by this teacher teflreflections.wordpress.com/2014/11/20/past-simple-pres...
As seen in this listicle of advice for startups when hiring new people into their business goodness.greatergood.com/retest-cs-startup-success/
Used in this blog post about how to use a blog to get a job (in addition to your CV website) www.unostips.com/blogcv-curriculum-vitae/
Featured in this business article about why so many interviewers misevaluate candidates with their questions www.alleywatch.com/2015/11/probably-suck-interviewing/
As seen in this blog post about how to read social cue during business meetings orgleader.com/meeting-impact/
Used in this blog post about MBA interview questions www.targetadmission.com/articles/mba-interview-questions-...
Featured in this blog post about how to moderate on-stage interviews with celebrities www.moderatingpanels.com/2017/02/when-your-moderation-gig...
As seen in this article about medical school admissions www.medical-school-insider.com/medical-school-admissions....
Used in this Japanese slideshow about Rakuten? www.slideshare.net/TakaoOyobe/20131106-change-hacker
I began designing this model in November of 2018, and I'm proud to announce that, finally, after months of building and rebuilding, testing and retesting, my Southern #1401 replica is complete and in flawless operating condition!
A big thanks to Andrew Mollmann of OKBrickWorks for the livening decals, and to Cameron Miller, Glenn Holland and Cale Leiphart for suggestions, tips and tricks.
Please enjoy the complete album on my personal Flickr page and be sure to like/comment!
What a gorgeous dial! The best vintage Euro-continental radio dial on the planet. A radio over 50 years old that's flawless & sounds great.
Can you imagine a radio like this being mass-produced? You have people shellacing, waxing and rubbing the woodwork. Lots of geppeto poindexter types testing and retesting all the tabs and buttons over and over again. People in lab coats with those famous German eyeglasses that have the horizontal brass bar straight across the top over both lenses going over each unit with a fine-toothed comb and calipers. The silkscreeners working on the dial faceplate with all those German cities, inspecting each one with macro monacles to make sure none of the letters dripped or ran. And still others stretching the high-tensil string over the wheels and pulleys that run the tuning dial mechanism....two separate bar indicators, and the right knob has a front and rear rotor for a revolving antenna inside. And to think there were 90 different styles of radios manufactured in West Germany between a couple dozen companies in the year 1957 alone. Many of them had tuning that went from right to left in those days, and the FM bandwidth was only from 88 to 100 instead of 88 to 108. Back then the FM bandspead was shortened to accomodate at either end adjacent military and police bands.
Even the woodgrain top of this radio was cut into four sections from the same board stock...reversed left to right, cut down the center and flipped front to back into four equal panels to display grain symmetry, and merged seamlessly like the elevator door facades at the Rockefeller Plaza.
( EXPLORED!!! ) So, uh....I'm sorry about the mess an' all..... I'm guessing I didn't pass the test.... so..... let me know when the retest is..... gotta go!
Hello, my lovelies.
It's been far too quiet around these parts. For that, I offer my sincerest apologies.
I've been trying to get back on track, but I've been thrown a little off-kilter the past few weeks. And, in some respects, the past few months.
My last post here was pre-scheduled. Which was handy, given I was sequestered (willingly!) in a friend's flat with her kitteh, Mia, and the slowest iMac known to woman (the last bit, not willingly!).
Unfortunately, that weekend also marked the beginning of a heatwave here in London.
Had I been home, the temperatures would have been higher than I'd have liked but manageable. However, in a first-floor flat with a curious kitteh, the windows could only be opened a small amount. When Mia wasn't hiding from the heat in a drawer under the bed, she was perched on the window openings cooling her tush.
Consequently, I spent most of the weekend lounging under a 10cm fan and keeping Mia company in her hatred of the heat.
The sun's emanations were too much for me to endure to see through my plan to visit some distinctive housing in the nearby neighbourhoods. Or to visit the Brockley and Ladywell Cemetery, as I had planned. Next time, Gadget, next time.
A busy but part-time week of work followed 'hot' on the heels of that.
I managed to sneak in some socialising outside my flat on Friday despite my ongoing health issues. Followed by a weekend of socialising inside my flat and hiding as much as possible from the heat.
The hottest day on record in the UK and the day preceding it blew out any plans I had for productivity outside my day job the following week.
It took most of the week to get my bedroom back down below 30 degrees, even at night. When it finally cooled almost enough, I celebrated by creating a Spotify playlist.
Health issues scuppered plans to walk the remaining section of the New River between Harringay Green Lanes Overground Station and Manor House/Finsbury Park with Scott and our cameras last Friday. At least we managed a pleasant afternoon of beers, ciders and conversation in place of that (with a detour to my GP's office).
On the positive side, at least I found out that day that the fatigue I've been feeling the past month or so wasn't just my imagination and or me being lazy. I'm vitamin D deficient and have low levels of vitamin B12 again. The former is being managed with some heavy-duty supplements. The latter requires retesting in six weeks. If still low, it will mean injections as I had back in 2007. Between now and then, I need to see if I can improve things from a dietary perspective to pump them back up a bit.
My other ongoing health issue hasn't been 100% diagnosed yet. I've been referred for further testing, but I have a new medication I started yesterday. That will hopefully manage the issues and get me back to photo walks and day trips soon enough. Fingers crossed.
Though, between dreams about the medication and my new bite guard, I've not had the best sleep the past few nights!
This is the first night I've managed to keep being creative after midnight for weeks. For someone who's a night owl and for whom this time is usually my most productive time, that has been beyond frustrating. I suspect this is because I took a long lunch today to nap for an hour and a half.
I hope to share more posts later in the day. And schedule new work for the weekend as I'll be away from home cat-sitting Lily, Sammy and Poppy from Thursday evening to Monday evening.
I'm also still working on my chapbook and other creative things. They're just taking far longer than I would have liked.
Thank you for your patience through all this.
I posted this early access for my Patreon patrons a few days ago.