Characteristics of SARS-CoV-2 and Covid-19(nature.com)
nature.com
Characteristics of SARS-CoV-2 and Covid-19
https://www.nature.com/articles/s41579-020-00459-7
43 comments
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We should extend lockdowns and close all businesses.
This paper made me realize just how much info I have been bombarded with since february. This feels like a distilled set of Cliffs Notes from the past 8 months.
I find this paragraph to be too neutral about HCL, and tbh a bit out of date:
> Chloroquine and hydroxychloroquine are other potential but controversial drugs that interfere with the entry of SARS-CoV-2. They have been used in the prevention and treatment of malaria and autoimmune diseases, including systemic lupus erythematosus and rheumatoid arthritis. They can inhibit the glycosylation of cellular receptors and interfere with virus–host receptor binding, as well as increase the endosomal pH and inhibit membrane fusion. Currently, no scientific consensus has been reached for their efficacy in the treatment of COVID-19. Some studies showed they can inhibit SARS-CoV-2 infection in vitro, but the clinical data are insufficient. Two clinical studies indicated no association with death rates in patients receiving chloroquine or hydroxychloroquine compared with those not receiving the drug and even suggest it may increase the risk of dying as a higher risk of cardiac arrest was found in the treated patients130,131. On 15 June 2020, owing to the side effects observed in clinical trials, the US Food and Drug Administration (FDA) revoked the emergency use authorization for chloroquine and hydroxychloroquine for the treatment of COVID-19
The in vitro studies that showed HCL efficacy were using vero lines, basically kidney cells. Those cells don't express the TMPRSS2 receptor, which is expressed on lung cells though. Studies have shown since that if you modify vero lines to express TMPRSS2, or use lung cells instead of kidney cells, HCL has no effect. It's kinda understandable that the earlier studies have used vero lines, because it's a standard cell line. But research has moved on since. The newer study has come out in July and should have been known to the authors of this review.
https://www.nature.com/articles/s41586-020-2575-3
> Chloroquine and hydroxychloroquine are other potential but controversial drugs that interfere with the entry of SARS-CoV-2. They have been used in the prevention and treatment of malaria and autoimmune diseases, including systemic lupus erythematosus and rheumatoid arthritis. They can inhibit the glycosylation of cellular receptors and interfere with virus–host receptor binding, as well as increase the endosomal pH and inhibit membrane fusion. Currently, no scientific consensus has been reached for their efficacy in the treatment of COVID-19. Some studies showed they can inhibit SARS-CoV-2 infection in vitro, but the clinical data are insufficient. Two clinical studies indicated no association with death rates in patients receiving chloroquine or hydroxychloroquine compared with those not receiving the drug and even suggest it may increase the risk of dying as a higher risk of cardiac arrest was found in the treated patients130,131. On 15 June 2020, owing to the side effects observed in clinical trials, the US Food and Drug Administration (FDA) revoked the emergency use authorization for chloroquine and hydroxychloroquine for the treatment of COVID-19
The in vitro studies that showed HCL efficacy were using vero lines, basically kidney cells. Those cells don't express the TMPRSS2 receptor, which is expressed on lung cells though. Studies have shown since that if you modify vero lines to express TMPRSS2, or use lung cells instead of kidney cells, HCL has no effect. It's kinda understandable that the earlier studies have used vero lines, because it's a standard cell line. But research has moved on since. The newer study has come out in July and should have been known to the authors of this review.
https://www.nature.com/articles/s41586-020-2575-3
The circumstantial evidence of HCQ being positive is substantial, and at least some of the complaints against it are politically motivated. Although how being hopeful about a COVID treatment became a pro-Trump political stance is beyond me.
They can wait until the scientific evidence is overwhelming. No hurry, there are a lot of studies starting to come due. Bodies are complex and maybe something is going on that hasn't been thought of yet.
EDIT Thanks swebs for the HCL->HCQ correction.
They can wait until the scientific evidence is overwhelming. No hurry, there are a lot of studies starting to come due. Bodies are complex and maybe something is going on that hasn't been thought of yet.
EDIT Thanks swebs for the HCL->HCQ correction.
Seems like your wait is over. From the second half of [0]:
> Hydroxychloroquine treatment for coronavirus does not work. It is not beneficial, and in fact appears to be actively harmful. As far as I’m concerned, administering it to infected patients now constitutes medical malpractice.
Check the linked article for reference to the study.
0: https://blogs.sciencemag.org/pipeline/archives/2020/10/09/ha...
> Hydroxychloroquine treatment for coronavirus does not work. It is not beneficial, and in fact appears to be actively harmful. As far as I’m concerned, administering it to infected patients now constitutes medical malpractice.
Check the linked article for reference to the study.
0: https://blogs.sciencemag.org/pipeline/archives/2020/10/09/ha...
"As far as I’m concerned, administering it to infected patients now constitutes medical malpractice. I have no interest in goalpost-moving efforts to say that they didn’t administer zinc or azithromycin, or they picked the wrong patients or the wrong loading dose or whatever. No."
The original treatment protocol included zinc, so it's nonsense to say that adding in zinc is "moving the goalpost". Not testing in combination with zinc is moving the goalpost. The interaction between zinc and HCQ is key. Azithromycin is just to prevent potential secondary bacterial infection, which isn't necessarily a big factor in COVID mortality.
"This is special pleading, and it is not backed up by any hard data."
Here's a study that showed adding zinc to HCQ reduced mortality by 50%:
https://pubmed.ncbi.nlm.nih.gov/32930657/
Unfortunately, that study didn't test zinc without HCQ, but the hypothesis is that HCQ acts as an ionophore and is therefore beneficial.
The original treatment protocol included zinc, so it's nonsense to say that adding in zinc is "moving the goalpost". Not testing in combination with zinc is moving the goalpost. The interaction between zinc and HCQ is key. Azithromycin is just to prevent potential secondary bacterial infection, which isn't necessarily a big factor in COVID mortality.
"This is special pleading, and it is not backed up by any hard data."
Here's a study that showed adding zinc to HCQ reduced mortality by 50%:
https://pubmed.ncbi.nlm.nih.gov/32930657/
Unfortunately, that study didn't test zinc without HCQ, but the hypothesis is that HCQ acts as an ionophore and is therefore beneficial.
> The original treatment protocol included zinc
Eh? No, it didn't. People started talking about zinc when it became clear that Raoult's results weren't reproducible.
Eh? No, it didn't. People started talking about zinc when it became clear that Raoult's results weren't reproducible.
You're right about Raoult not mentioning zinc, but Zelenko used zinc from the beginning.
Also, significant reduction in mortality using HCQ alone early during the treatment has been reproduced:
https://www.medrxiv.org/content/10.1101/2020.09.09.20184143v...
The earlier trials weren't testing prophylactic treatment.
Also, significant reduction in mortality using HCQ alone early during the treatment has been reproduced:
https://www.medrxiv.org/content/10.1101/2020.09.09.20184143v...
The earlier trials weren't testing prophylactic treatment.
Switzerland accidentally performed such an experiment on their population as well - also showing HCQ saves lives: http://www.francesoir.fr/sites/francesoir/files/20200713_fs_...
Image from http://www.francesoir.fr/societe-sante/covid-19-hydroxychlor...
Image from http://www.francesoir.fr/societe-sante/covid-19-hydroxychlor...
One of my favourite posts on HN was some gentleman telling me that masks didn't help against COVID, that the science was in, and that I was endangering lives by even suggesting something so stupid when either the WHO or CDC or Fauci had debunked the idea. I think that was back around April.
My current policy is to wait until the evidence is older than a week. That is one open label study on patients that were already in hospital - strong evidence, but not a final word. Maybe they missed something, maybe they made a mistake. Science is hard.
My current policy is to wait until the evidence is older than a week. That is one open label study on patients that were already in hospital - strong evidence, but not a final word. Maybe they missed something, maybe they made a mistake. Science is hard.
> My current policy is to wait until the evidence is older than a week. That is one open label study on patients that were already in hospital - strong evidence, but not a final word. Maybe they missed something, maybe they made a mistake. Science is hard.
Indeed: https://www.sciencedirect.com/science/article/pii/S120197122...
I'd say it's not conclusively settled yet.
Indeed: https://www.sciencedirect.com/science/article/pii/S120197122...
I'd say it's not conclusively settled yet.
The truth of the efficacy of hydroxy chloroquine to treat covid may not be settled.
But what is settled is that there is not enough conclusive evidence right now to use it as a treatment.
In medicine, when confronted with low degrees of certainty, the default is to -not- administer to treatment until proven otherwise.
As a side note, notice that it appears Trump did not receive HCQ as part of his treatment regiment.
But what is settled is that there is not enough conclusive evidence right now to use it as a treatment.
In medicine, when confronted with low degrees of certainty, the default is to -not- administer to treatment until proven otherwise.
As a side note, notice that it appears Trump did not receive HCQ as part of his treatment regiment.
I think you're making false equivalences.
To be clear, there has never been good scientific evidence that masks are ineffective against respiratory viruses. I think WHO, CDC and Fauci made grave errors at the time by making the argument that mask-wearing by the general public "doesn't work". The clear (and quite understandable) fear was that there would be a run on masks by the general public, so instead of telling the truth ("we need the masks for healthcare workers") they made broader and confusing statements about the effectiveness of masks that were not supported by the underlying science. This had the terrible effect, as your post shows, of making people even more wary of scientific pronouncements. Mine is not an isolated viewpoint. There was a good opinion article in the Washington Post at the time by an influential researcher where she argued the same thing.
Contrarily, the good studies that have come out about HCQ have nearly uniformly shown their potential danger. There is simply no equivalence between the scientific data that HCQ is harmful and the data (that never existed mind you) that mask-wearing is ineffective.
To be clear, there has never been good scientific evidence that masks are ineffective against respiratory viruses. I think WHO, CDC and Fauci made grave errors at the time by making the argument that mask-wearing by the general public "doesn't work". The clear (and quite understandable) fear was that there would be a run on masks by the general public, so instead of telling the truth ("we need the masks for healthcare workers") they made broader and confusing statements about the effectiveness of masks that were not supported by the underlying science. This had the terrible effect, as your post shows, of making people even more wary of scientific pronouncements. Mine is not an isolated viewpoint. There was a good opinion article in the Washington Post at the time by an influential researcher where she argued the same thing.
Contrarily, the good studies that have come out about HCQ have nearly uniformly shown their potential danger. There is simply no equivalence between the scientific data that HCQ is harmful and the data (that never existed mind you) that mask-wearing is ineffective.
Yeah, the mask thing was one gigantic communications failure. I#ll give them the benfit of doubt, so, and asume they really believed COVID-19 was mostly transmitted through surfaces and less through droplets. Which would make masks less effecitive. Regardless, it was a gamble, one that didn't pay off considering all the rediculous discussions about masks right now. But then I am almost sure we would have the same discussions about other things, or even masks, if communication had been done differently.
Btw, as you bring up politics, Trump's own doctors, who absolutely know what they are doing, gave him a long list of medications, including some experimental ones which weren't even ermergency approved by the FDA yet, but that list did not include HCL.
https://www.boston25news.com/news/trending/trump-coronavirus...
https://www.boston25news.com/news/trending/trump-coronavirus...
It's indeed curious, also Trump at one point claimed to be taking HCQ prophylactically, I wonder how far that went.
Having said that, giving somebody "experimental treatment" and "knowing what one is doing" is contradictory. According to Trump, he asked for the experimental antibody therapy himself. As his doctor, you then have the choice of playing the odds or putting "got fired by Trump" on your resume.
Having said that, giving somebody "experimental treatment" and "knowing what one is doing" is contradictory. According to Trump, he asked for the experimental antibody therapy himself. As his doctor, you then have the choice of playing the odds or putting "got fired by Trump" on your resume.
I think putting "got fired by Trump" on your resume would be a badge of integrity and honor.
Any discussion of HCQ that ignores zinc, a key part of the original treatment protocol, is missing the mark.
Rationale:
https://www.sciencedirect.com/science/article/pii/S030698772...
Trial:
https://pubmed.ncbi.nlm.nih.gov/32930657/
Rationale:
https://www.sciencedirect.com/science/article/pii/S030698772...
Trial:
https://pubmed.ncbi.nlm.nih.gov/32930657/
A paper published in Nature is being criticized as "too neutral" for pointing out that the evidence is inconclusive.
My comment is getting heavily downvoted, despite being properly sourced. No counter-argument or evidence is presented.
Why? Does nobody care to explain themselves?
My comment is getting heavily downvoted, despite being properly sourced. No counter-argument or evidence is presented.
Why? Does nobody care to explain themselves?
Maybe your negative tone or the low information density. I guess just dropping links is frowned upon. You could have written a short summary or at least paste the TLDR from these papers and then link to the sources.
>HCL
It's a bit weird to use that as an acronym for hydroxychloroquine when everybody already uses it for hydrochloric acid (Hydrogen Chloride).
It's a bit weird to use that as an acronym for hydroxychloroquine when everybody already uses it for hydrochloric acid (Hydrogen Chloride).
HCL and HCl would be very different things to a chemist, though, if an element L would actually exist.
Thanks for pointing this out. Shows that I'm no chemist :). According to Wikipedia the common abbreviation is HCQ instead of HCL. HN won't let me edit my post any more, otherwise I'd revise my comment.
"Currently, our knowledge on the animal origin of SARS-CoV-2 remains incomplete to a large part."
So we still have no proof of SARS-CoV-2 originating from natural selection, just as we have no proof of human intervention. I often read the first hypothesis is far more likely than the second, but I do not agree. The actual probabilities to be compared are:
- the likelihood of a virus outbreak due to natural selection in Wuhan
- the likelihood of a virus resulting from a gain of function experiment "escapes" from Wuhan BSL4
Note that we are sure that Wuhan BSL4 was doing gain of function experiments. Also note that natural virus outbreaks are quite likely when looking at China as a whole, China is big, or even when looking at the whole world. But that does not answer the question at hand, and that does not make the natural selection hypothesis "far more likely".
So we still have no proof of SARS-CoV-2 originating from natural selection, just as we have no proof of human intervention. I often read the first hypothesis is far more likely than the second, but I do not agree. The actual probabilities to be compared are:
- the likelihood of a virus outbreak due to natural selection in Wuhan
- the likelihood of a virus resulting from a gain of function experiment "escapes" from Wuhan BSL4
Note that we are sure that Wuhan BSL4 was doing gain of function experiments. Also note that natural virus outbreaks are quite likely when looking at China as a whole, China is big, or even when looking at the whole world. But that does not answer the question at hand, and that does not make the natural selection hypothesis "far more likely".
The outbreak happening in Wuhan does not mean that the virus originated there. In the beginning there was more genetic variety seen in Guangdong, which is a sign that the virus originated there and not in Wuhan.
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The outbreak has always been claimed to occur in Wuhan's "wet market". The article only mentions pangolin coronavirus strains in relation to Guangdong. There is no assumption in the article SARS-CoV-2, the human virus, could originate from Guangdong. Should SARS-CoV-2 actually originate from Guangdong would anyway be the sign of a huge dissimulation.
My understanding is that many scientists have concluded that animal->human adaptation occurred prior to the Wuhan wet market, and the market is basically a red herring. This is based on the relatively low degree of genetic drift that has occurred with SARS-Cov-2 since that time, which indicates that the substantial changes related to human adaptation are likely to have occurred prior to those wet market infections. There are better articles, but here's one [1].
[1] https://www.livescience.com/covid-19-did-not-start-at-wuhan-...
[1] https://www.livescience.com/covid-19-did-not-start-at-wuhan-...
Incomplete knowledge =/= no proof. From what I got, I am no virologist, is that it is experts consense that the virus jumped from animals to humans. It is just the details we don't know yet.
And please, stop spreading this "Wuhan-lab-escaped-engineered-virus" BS.
And please, stop spreading this "Wuhan-lab-escaped-engineered-virus" BS.
If you read the article carefully, it leaves the two options open, refusing to conclude, with a preference towards a natural mutation. BTW the virus may have jumped from animals to humans inside the lab itself. What is BS is "mutations occur in the wild permanently, so that's the most likely hypothesis". In this particular case, that's unfounded and specifically what I am challenging.
What good does it if we discuss such a sensitive issue without solid proof? There are thousands of other theories that have no supporting evidence. Some of them may even be true but most are just BS that takes up time. So let's wait with this discussion until there really is solid evidence for a theory.
We are probably never going to get solid proof either way. The lab origin hypothesis hasn't been ruled out. Yuri Deigin posted an interesting analysis with some circumstantial evidence.
https://medium.com/@yurideigin/lab-made-cov2-genealogy-throu...
There have been at least four other coronaviruses which crossed over from animals to humans before we had any real viral manipulation technology. So I suspect SARS-CoV-2 followed the same natural pattern. But that's still just a hypothesis, not proof.
https://medium.com/@yurideigin/lab-made-cov2-genealogy-throu...
There have been at least four other coronaviruses which crossed over from animals to humans before we had any real viral manipulation technology. So I suspect SARS-CoV-2 followed the same natural pattern. But that's still just a hypothesis, not proof.
If you demand absolute proof of every (negative) claim, then you're going to be unable to function in the world. In practice, the important question is: "is there enough evidence for this extraordinary hypothesis that it should influence our response going forward." Right now, the answer seems to be negative.
Understanding the origin of SARS-CoV-2 is irrelevant to how we handle the current pandemic. But it would be useful for reducing the risk of another similar pandemic in the future.
Understanding the origin of the pandemic is incredibly valuable. Continuing to moot about the possibility of lab origin in the absence of any positive evidence in favor of that hypothesis, that’s not terribly useful.
The animal transmission is, as far as I understood, backed up by genetic analysis of the virus. Which beats any circumstantial "evidence" by a long shot if you ask me.
Based on genetic analysis there is no doubt that an ancestor of the current SARS-CoV-2 strains originated in animals. What remains unknown is exactly how it crossed over to humans. The index patient hasn't been identified. Some sort of laboratory involvement seems unlikely, but we can't reject any hypothesis without definitive evidence.
Isn't it ususally that you proof hypothesis are correct instead of proofing them wrong?
This "I'm just asking, because it could theoretically be true" stuff is slowly getting tiresome.
This "I'm just asking, because it could theoretically be true" stuff is slowly getting tiresome.
No that is not at all how it usually works. The essence of the scientific method is formulating a hypothesis and then conducting experiments in an attempt to falsify it. The more experiments that have failed to falsify a hypothesis, the more confidence we can have in it.
https://en.wikipedia.org/wiki/Falsifiability
As a basic matter of epistemology we can almost never really prove a hypothesis. All we can do is agree that it fits the available data until something better comes along.
https://en.wikipedia.org/wiki/Falsifiability
As a basic matter of epistemology we can almost never really prove a hypothesis. All we can do is agree that it fits the available data until something better comes along.
Until you found proof for a hypothesis to be correct. At witch point you usually stop trying to falsify that hypothesis. Applying that to the Wuhan lab theory, the correct way would be to properly falsify the natural jump from animals to humans first. Scientifically falsifying it. I have yet to see such proof.
EDIT: Of course these proofs have a certain likelihood of being false, hence all the p-value chasing and confidence-level adjusting.
EDIT: Of course these proofs have a certain likelihood of being false, hence all the p-value chasing and confidence-level adjusting.
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