Origins of Covid

[W.D.Clinger]

Originally Posted by angrysoba

Are you talking about Quay's Bayseian analysis?

I have skimmed through the paper and I cannot make head or tail of his argument. It just looks like he arbitrarily attaches probabilities to cherry-picked datapoints.

That is a better abstract of the paper than the abstract Quay wrote.

Originally Posted by Skeptic Ginger

No, not that paper. Give me a few minutes and I'll edit the link in here.

Originally Posted by Skeptic Ginger

No, not that paper. Give me a few minutes hours (I got busy with other things) and I'll edit the link in here.

This is the paper you say you didn't understand:
A Bayesian analysis concludes beyond a reasonable doubt that SARS-CoV-2 is not a natural zoonosis but instead is laboratory derived
If you recall, you dismissed Quay not based on the paper but on the fact you weren't impressed by his background.

angrysoba asked whether that was the paper your meant, you said it wasn't, and now it appears to have been the paper you meant.

That paper is rubbish, for the substantive reason stated above by angrysoba. If I remember correctly, I have given a more substantive review of that paper earlier in this thread, and will try to find that review if SkepticGinger continues to refer to it.

[Skeptic Ginger]

Originally Posted by angrysoba

That is not what is being claimed, as far as I can see.

They claim it came from the same market as both lineages were present at the market.

So how is that evidence for a natural spillover? That doesn't make any sense.

It also doesn't address the problem those lineages might only differ because of sequencing error.

And it doesn't address the problem that the virus appeared out of the box adapted to humans. Replicating in an animal source wouldn't be expected to have produced 2 different variants both well adapted to human to human transmission and significant disease.

[Skeptic Ginger]

Originally Posted by angrysoba

I don't think this is correct. There is no claim that the civets were infected in the markets.

Yeah there was.

No reservoir was found among the civet cats or the other suspected source animal. But there were bats sold in the same markets.

Originally Posted by angrysoba

Civets had presumably been infected with SARS somewhere close to where the bats lived, in Yunnan.

If that had been the case then there would have been a reservoir in civets.

Originally Posted by angrysoba

(infected civets also showed up in other areas such as Shenzhen - which is where, I believe, infected civets were originally discovered, and also in Hubei, the province in which Wuhan is. This is circumstantial evidence that there is a plausible route from the countryside to Wuhan).

No, I reviewed this stuff before I posted. If you have a different history of how SARS was spread to humans you'll need to cite some sources so I can see what you are talking about.

Originally Posted by angrysoba

So nobody is looking for bats in the Huanan Market. It is irrelevant whether there were bats, live or otherwise there.

However, from what I gather Worobey et al do think that raccoon dogs were sold in the Huanan Market and they may have been infected somewhere on the wildlife trade route.

Right, he simply fills in the blanks where his hypothesis lacks evidence and acts as if that is all evidence supported.

Originally Posted by angrysoba

I think you should either read the Twitter thread that I linked to above in which Worobey summarizes the findings of the writers of the article (there are 18 authors altogether with impressive credentials), or maybe go straight to the paper itself.

In fact, it is one of two papers out right now which make the case for spillover.

I admit that I have not yet read them myself, and they have not been peer-reviewed yet, but I lack the competence in this field to make any critical appraisal of them. I can only go on the word of others in the field.

You want me to read something you haven't even read yourself?

I listened to the news reports, NPR had a lot of details plus someone who was supposed to be critiquing the report who actually was more someone posting confirmation bias than rebuttal.

Look, my reply was very thorough. If all you have is telling me to read the Twitter feed, (like when you said I should read the book, Spillover) that's not going to cut it.

Critique or rebut my post with specifics or something more concrete than your 'feelings' about a source and I'll reply to that.

I said initially that Worobey had an hypothesis. Bloom said he couldn't fault the science but it wasn't conclusive or a smoking gun. Now Worobey has expanded on his hypothesis but has added very little in the way of new evidence.

I don't see that the needle moved any amount at all.

[Skeptic Ginger]

Here's one of the sources I reviewed on the origin of SARS 1:

Berkeley evo news: Tracking SARS back to its source; January 2006, updated July 2013

Quote:

Scientists immediately suspected that it had jumped to humans from some other organism. In May of 2003, attention focused in on cat-like mammals called civets. Infected civets were discovered at a live animal market in southern China (where they are occasionally eaten). However, since further searches failed to turn up more tainted civets, scientists concluded that they were not the original source of SARS ...

They still knew or strongly suspected the 'spillover' originated in the proximal source, the civet cats.

Quote:

... and continued their quest. Then in the fall of 2005, two teams of researchers independently discovered large reservoirs of a SARS-like virus in Chinese horseshoe bats. The bats now appear to be both culprit and victim in this mystery: they are the carriers of the SARS virus, but the virus is probably only passed to humans through intermediate hosts when bats are captured and brought to market.

So bats to intermediate host to humans all in the wet markets.

Quote:

Viruses evolve rapidly and constantly, changing within a lineage and splitting off to form new lineages. As they evolve, they accumulate small changes in the sequences of their genomes. Based on these genetic differences, biologists can reconstruct the evolutionary relationships of different viral strains, building an evolutionary tree that reveals which strains evolved from which strains and in what order they evolved.

In this case, biologists collected samples of the SARS virus’s genetic material, RNA, from different sources: infected humans, infected civets, and different species of infected horseshoe bat. The RNA was then copied, sequenced, and used to build a phylogeny, or evolutionary tree.

The tree showed that civet and human SARS viruses are very similar to each other and, most importantly, that both are nested within a clade of bat viruses — so the ancestor of the civet and human strains seems to have been a bat virus! Based on this evidence, biologists have come up with a plausible path of transmission: infected bats and uninfected civets came into contact at a market, the virus was transmitted to civets and then multiplied and evolved in civets (or other animals) in the public market, until eventually the virus hopped to humans.

Notice Worobey has not found the clade that SARS 2 was nested within.

[angrysoba]

SG, thanks for the links regarding the question of how the civets became infected by SARS. I will have to look back into how I came to the conclusion that they were infected outside the markets because I cannot remember. It may have been that I read it in Spillover, or perhaps I heard it on a TWiV episode with the assumption being that the civets had been infected somewhere along the wildlife trade route, but not sure. But I also remember that infected civets (or at least those with antibodies against SARS) had turned up in multiple cities (including Shenzhen where, I believe the first civets were found, as opposed to Guangdong where the outbreak began, and in parts of Hubei), and people in Yunnan had tested positive for antibodies.

The article you posted is itself rather old, and it wasn't until 2017 that the virus was traced back to the particular bats in Yunnan province, so I am not sure if that work supersedes the article you posted.

Anyway, I will look into it.

[angrysoba]

Originally Posted by Skeptic Ginger

Right, he simply fills in the blanks where his hypothesis lacks evidence and acts as if that is all evidence supported.

I don't think this is fair. He is not "simply filling in the blanks" where his hypothesis lacks evidence. There is photographic evidence of raccoon dogs in the market taken by Eddie Holmes who is one of the co-authors. In fact there are 18 scientists on the paper, so it is not as though it is a single person just making up crap.

[angrysoba]

This is a pretty interesting thread from Kristian Andersen on the two pre-prints laying out the case for the market being the epicentre of the pandemic.

Link

Well recommended!

[angrysoba]

Dr Steven Quay has tweeted his reaction to the preprints (including a separate one that was done by the Chinese CDC under George Gao):

[angrysoba]

According to Vincent Racaniello, Michael Worobey says he will be on TWiV sometime soon. It will be interesting to see what he has to say. It is possible that he may go on with Robert Garry, or Kristian Andersen as well. Amy suggested having Daszak on as well to see what he makes of it.

[Skeptic Ginger]

Originally Posted by angrysoba

SG, thanks for the links regarding the question of how the civets became infected by SARS. I will have to look back into how I came to the conclusion that they were infected outside the markets because I cannot remember. It may have been that I read it in Spillover, or perhaps I heard it on a TWiV episode with the assumption being that the civets had been infected somewhere along the wildlife trade route, but not sure. But I also remember that infected civets (or at least those with antibodies against SARS) had turned up in multiple cities (including Shenzhen where, I believe the first civets were found, as opposed to Guangdong where the outbreak began, and in parts of Hubei), and people in Yunnan had tested positive for antibodies.

The article you posted is itself rather old, and it wasn't until 2017 that the virus was traced back to the particular bats in Yunnan province, so I am not sure if that work supersedes the article you posted.

Anyway, I will look into it.

I believe you might be conflating when the specific bat virus was found to be the source of SARS 1 with the finding the Yunnan horseshoe bats harbored multiple SARS-like coronaviruses. I don't know without reviewing the papers either.

As for where else infected Civets showed up, I'd need to look into that as well. There was no other location for where SARS 1 jumped to people. That was all in Guangdong. It was a one-time jump from two different wet markets at about the same time. I followed all this very closely at the time because I was advising employers and teaching healthcare workers how to manage potential SARS patients.

Worobey's claim to have found new evidence or whatever the latest headline reads is simply not true. His evidence is a nice tap-dance (think Chicago) using no new information.

I still have the Spillover book. I'l review what it said about the SARS 1 origin.

[Skeptic Ginger]

Originally Posted by angrysoba

I don't think this is fair. He is not "simply filling in the blanks" where his hypothesis lacks evidence. There is photographic evidence of raccoon dogs in the market taken by Eddie Holmes who is one of the co-authors. In fact there are 18 scientists on the paper, so it is not as though it is a single person just making up crap.

So there were raccoon dogs, so what? (That was a species also suspected of being the source of SARS 1 jump to people.)

I posted the list made before SARS 2 of animals sold at the wet markets in Wuhan. Raccoon Dogs are on the list as are civets also called Masked palm civet. Minks are also on the list. This is not new information. The article is from June 2021.

Nature, linked to recently but I might have also linked to it way back when pangolins were being discussed.

Table 1 from the article:Table 1 List of 38 species sold in Wuhan City markets between May 2017–Nov 2019, including the mean number of live individuals sold per month and price (mean ± SD; n = survey rounds).

[Skeptic Ginger]

Originally Posted by angrysoba

Dr Steven Quay has tweeted his reaction to the preprints (including a separate one that was done by the Chinese CDC under George Gao):

A link instead of this screenshot would be nice.

I'll hunt down his Twitter Feed and get back to this later. I don't have it on speed dial.


Edited to add: I appreciate it when you have these moments of actual discussion.

[angrysoba]

Michael Worobey appears on this episode of TWiV to explain why he says the market is the epicentre of the spillover.

Essentially, he argues that this was a repeat of SARS-1. Why was the trail not picked up on? Well, the animals were culled, the market was cleaned, some of the wildlife farms were disbanded, and one of the reasons it spread out so quickly to obscure the origins were because of asymptomatic spread which was not the case with SARS-1.

YouTube Video This video is not hosted by the ISF. The ISF can not be held responsible for the suitability or legality of this material. By clicking the link below you agree to view content from an external website.

I AGREE

Admittedly he is not a very engaging speaker, to be honest, but that should not be surprising as it is clearly not part of his skill set. Probably best to listen on x1.25 or even x1.5.

[Skeptic Ginger]

I've listened to the first hour, I'll listen to the last 44 minutes later. So far it's exactly what I said, he's ignored the data that doesn't fit his hypothesis and filled in data where none existed.

Let me step back a minute here and talk about Worobey.

Worobey and the group he worked with in the 80s did research on the origin of HIV. He was accused of pushing his hypothesis while ignoring some data and filling in some holes without data. In the case of HIV, unfortunately there was an actual CT that HIV was the product of vaccine development. There was no evidence for that hypothesis and since the work showing the airline steward was not patient zero, more evidence has been found and all of it corroborated the origin coming from bushmeat in the Congo.

Epidemiological evidence surfaced of cases of 'wasting' among persons in rural African villages that occurred in the 50s IIRC. A road was built to harvest logs and along that road prostitution flourished. It allowed HIV which had been confined to a small area to spread far and wide. There was also a direct connection to Haiti. Eventually the virus spread among homosexuals who were having encounters with 100s of partners.

The first point being we have a lot of corroborating evidence about the origin of HIV not being from vaccine development. And we have corroboration where HIV initially spilled-over, it's not based on one group's phylogenic mapping.

And the second point being, Worobey would almost certainly like to relive his glory days when he was involved in tracking down the origin of HIV.

So let's look at the data he conveniently ignores and adds to make this all fit his COVID spillover hypothesis.

We have lineage A & B. Worobey says they are only a couple mutations difference between them. I believe it is only 3. He starts off saying A came first and was found in those people who had no connection to the seafood market. (He ignores previous conclusions the market was the site of a super-spreader event.) Then suddenly they find a single specimen of the A lineage among the seafood market patients and nothing about all the other patients with A not being connected to that market matter anymore.

From there he speculates using words like "it's possible" B came first and the cases not connected to the seafood market "probably" had connections to the other 4 wet markets in the area.

He makes excuses why no infected source animals were found even going so far as to erroneously claim that wild animals might have been caught "around Wuhan" when no such potential source animals were found anywhere near Wuhan.

He thinks the cases connected to the seafood market are too much of a coincidence while ignoring the extraordinary coincidence the initial outbreak happened close to 2 labs studying related viruses. He noted the distance to the WIV (hardly impossible if a single staff member or student spread the virus from one of the labs). But he fails to mention the location of the CCDC lab very close to the market and doesn't mention that lab moved locations still close to the market around the time of the outbreak.

Like the strawman that keeps being repeated bioengineered viruses have been ruled out as if the lab leak origin relies on that (it doesn't), he adds a new strawman claiming people who favor the lab origin claimed certain wild animals weren't for sale at the market. I don't know anyone making such a claim, maybe Worobey does.

And so far it looks like his whole hypothesis relies heavily on multiple spillover events hitting dead ends before one successful event got started in Wuhan. The problem with this is it completely ignores the need for the virus to become adapted to person to person spread in humans.

He mentions spreading occurred in asymptomatic persons to get to lineage A from lineage B.

Supposedly of the first 14 or so cases, ~half were connected to the seafood market, ~half weren't. Then suddenly the total cases in Dec they are looking at is 164 of which 156 were lineage B. Well d'uh, B was more successful in spreading as shown by its continued spread. It wasn't because B was the first lineage in the spillover.

He wasn't very clear how the first cases were in Nov, then they were in Dec??? And there were only a dozen or so and all of a sudden there were 164 cases? That's some pretty fast spreading for a virus that only jumped from animals infecting a dozen or so cases to reach in less than a month.

But if you are Worobey filling in the evidence holes, you explain it all by asymptomatic cases. OK, then, how many cases were there in Oct or Nov? His phylogenic mapping doesn't go back before Dec. Why is that? Lineage A was supposed to be earlier than B and was found in the earliest cases. What happened to that when a single case of A was found in the seafood market samples? So those early cases of A no longer count as earlier? They must have been later all connected to asymptomatic cases?

Again other than multiple dead-end starts, nowhere does Worobey address the biggest problem with his hypothesis, how/where did SARS CoV2 become so well adapted to humans?

So far the other people in the podcast are not asking very hard hitting questions.


Worobey mentioned the 8 other genomes Shi did not put in the gene bank access. He asks Shi about it and she puts those genomes in the bank explaining they were less like SARS CoV2 than RaTG13. How do we know that? Shi is not likely going to post incriminating evidence online.

It so happens I am on that chapter in Viral, Chan and Ridley's book on the origin of SARS CoV2. I'll post about it when I finish the chapter.

[angrysoba]

I think the chapter on HIV in Spillover is quite good. It goes pretty deeply into the OPV theory of AIDS (which was that oral polio vaccine used a form of the simian version of AIDS which then led to the HIV and then AIDS) and also Worobey's involvement in initially accompanying W. D. Hamilton (a prominent proponent of the theory) to Congo to find blood samples in order to see if it contained SIV. Apparently Hamilton contracted malaria on the trip and later died, and the blood samples showed no SIV.

Regarding Worobey's theory here, the TWIV team don't really ask many questions because, as they say at the end, Worobey basically answers all the ones that they planned to ask, and they apparently had a lot that they wanted to ask.

Regarding the wild animals, I don't think Worobey thinks they came from near Wuhan, as far as I remember. They could have been farmed many miles away.

I also don't think he is arguing it spilled over in multiple markets. Just one.

How did it get adapted to humans? Well, presumably there is a survivorship bias. Lineage A was not as adaptive as B, and maybe there were others that fizzled out. We know it was adapting all the time as he even mentions another variant that completely took over.

And we can hardly say he is "ignoring" the proximity of the labs. It was the very proximity of the labs that got him and Jesse Bloom to write a letter to Science saying that the lab leak theory needs to be taken seriously.

Anyway, it will be interesting to see what the peer reviewers make of it.

[Skeptic Ginger]

Originally Posted by angrysoba

.... Regarding the wild animals, I don't think Worobey thinks they came from near Wuhan, as far as I remember. They could have been farmed many miles away.

He gave a number of possibilities none proven, none supported by any evidence.

Originally Posted by angrysoba

.... I also don't think he is arguing it spilled over in multiple markets. Just one.

He shifted his story. At first he said there was more than one event and he described the 4 nearby markets he hypothesized were the source of those infections not related to the seafood market. Later he shifted to saying instead because they found one case of lineage A at the seafood market all the lineage A cases not related to the market must have been (again no evidence) spread by asymptomatic cases. This is one of the things where he simply fit the data to his preconceived conclusion.

Originally Posted by angrysoba

.... How did it get adapted to humans? Well, presumably there is a survivorship bias. Lineage A was not as adaptive as B, and maybe there were others that fizzled out. We know it was adapting all the time as he even mentions another variant that completely took over.

No, not what the evidence shows and it is not what needs to happen for adaptation to human spread. But think about what you are saying: A was first. Worobey fitting the data to his preconceived bias said he later believed B was first. IOW it entered the human population ready to rapidly spread.

He can't have it both ways, A first then B makes it less adapted though not by much. Or B first then it was already highly contagious, no adaptation needed.

That's not what happened with SARS 1 which simmered for about a month among people before becoming well adapted to human to human spread.

And HPAI H5N1 (flu) has yet to become adapted to human to human spread after a number of human cases and almost 20 years! The first human cases were in 1997 (IIRC) in Hong Kong CDC says 2003. At some point it was found the virus was only a couple mutations away from adapting to human spread.

Also he mentioned the furin cleavage site but did not explain when that fit into the picture other than it supposedly happened before the jump. How was that mutation naturally selected?

Originally Posted by angrysoba

.... And we can hardly say he is "ignoring" the proximity of the labs. It was the very proximity of the labs that got him and Jesse Bloom to write a letter to Science saying that the lab leak theory needs to be taken seriously.

And after that he does his genetic mapping (which only goes back to Dec 10) and claims the epidemiological evidence corroborates that with the cluster of cases he maps around the seafood market. The CCDC lab near the market is not mentioned in the first hour anyway. I still have 44 minutes to go.

[angrysoba]

Originally Posted by Skeptic Ginger

That's not what happened with SARS 1 which simmered for about a month among people before becoming well adapted to human to human spread.

And HPAI H5N1 (flu) has yet to become adapted to human to human spread after a number of human cases and almost 20 years!

These two objections taken together make no sense, do they?

If you are expressing incredulity that SARS-CoV2 apparently became adapted so quickly on the basis that it did so faster than SARS-1, then by your own argument you should also express incredulity that SARS-1 became human-to-human adapted in merely a month when *points at random flu* that one still hasn't after 20 years.

[Skeptic Ginger]

Originally Posted by angrysoba

These two objections taken together make no sense, do they?

If you are expressing incredulity that SARS-CoV2 apparently became adapted so quickly on the basis that it did so faster than SARS-1, then by your own argument you should also express incredulity that SARS-1 became human-to-human adapted in merely a month when *points at random flu* that one still hasn't after 20 years.

This is bizarre logic.

Neither one 'spilled over' ready to go with rapid human to human spreading.

[angrysoba]

Originally Posted by Skeptic Ginger

This is bizarre logic.

Neither one 'spilled over' ready to go with rapid human to human spreading.

I think you have pointed out, very clearly, that different viruses require different time frames to become human-to-human transmissable.

In addition, do you know who the first person to get Covid was?

[Skeptic Ginger]

Originally Posted by angrysoba

I think you have pointed out, very clearly, that different viruses require different time frames to become human-to-human transmissable.

In addition, do you know who the first person to get Covid was?

China is hiding that information. Worobey didn't know either.

It's a basic principle in biology that a virus jumping species has to adapt to the new species. But there are exceptions. For example COVID adapted quickly to deer and mink.

The thing is, if one sees a virus appear in humans that is ready to go, the lab is much more likely to be the source. It is not proof.

And there are a couple of suspicious mutations like the furin cleavage mutation which are hard to explain as some random natural mutation. That becomes quite a coincidence. Again, it is not proof.

And speaking of other animals, COVID has spread rapidly in deer and mink and yet no evidence of it circulating in other species in China has been found*.

Scientists have now found the coronavirus in 29 kinds of animals,

Quote:

a list that has been steadily growing almost since the start of the pandemic and includes cats, dogs, ferrets, hamsters, tigers, mice, otters and hippos. In most cases, the animals have not been shown to transmit the virus back to humans.

But in at least two cases, it looks as if they can. Minks have spread the virus to people, and in a new Canadian study, scientists identified one person who tested positive after unspecified “close contact” with infected white-tailed deer.

This is more evidence the virus should have been found in other species in China yet it hasn't been. Worobey claims the Chinese tested irrelevant species in that 80,000 tested. But once again he fits the evidence to his preconceived conclusion.


*Evidence it has now been found in pets in China is after the fact. So far it has shown up in animals exposed to infected people, not the other way around.

[Skeptic Ginger]

Delete, Deny, and Destroy: Chinese and Western Strategies To Erase COVID’s Origin Are Being Exposed By Independent Research; by Jonathan Latham, PhD and Allison Wilson, PhD

This is an excellent and very thorough article that tears down both the Worobey hypothesis and the Chinese CDC attempt to focus the blame outside of China.

Quote:

A Huanan market origin has officially been dismissed by the authorities in China. Nevertheless, on February 25th a preprint authored by George Gao, head of China’s CDC, and 38 other Chinese virologists appeared that seems intended to settle the issue (Gao et al., 2022). ...

Just sixteen hours later, on February 26th, two preprints appeared simultaneously that directly contradict the Gao conclusions. The senior authors of these companion articles are an overlapping set of very high-profile virologists. None are from China.

One of these preprints asserts, based on surface swabs and other environmental samples found there, that the Huanan market was the “unambiguous epicenter” of the pandemic (Worobey et al., 2022). The second argues that SARS-CoV-2 emerged at least twice at the market (Pekar et al., 2022). According to these latter authors, one zoonotic spillover created what are known as the lineage A SARS-CoV-2 viruses and a second spillover was the root of all lineage B SARS-CoV-2 viruses. These two spillovers, they say, decisively contradict a lab leak.

Quote:

Especially if one includes the new Gao et al. evidence, there are already powerful reasons to doubt both the market-zoonotic origin and a dual-spillover. These reasons are largely glossed over by the Pekar and Worobey preprints so they are worth outlining briefly:

I won't rehash the reasons to doubt the Worobey work but do read the specifics outlined very carefully in this paper.

This piece of evidence is important and I'm not sure it was mentioned before:

Quote:

2) Environmental samples collected at the market are of human origin and did not come from animals sold there.

And this is essentially what I said about conveniently filling in the holes in the evidence:

Quote:

3) Pekar and Worobey rely on circular reasoning to identify root viruses.

Not only is the evidence lacking for 2 spillover events, it's lacking for even one such event.

There's a very interesting discussion of bad science by good scientists that everyone in this forum should find interesting whether they care about the origin debate or not.

Quote:

It is a reasonable inference from the above that the leading virologists on each side, and who are directing these efforts, strongly suspect (or know because they are sitting on the evidence) that early data would not exonerate virus research in Wuhan, otherwise the same people would be hunting for early samples with great alacrity, which is clearly not happening. And we can surmise it is a lab leak that is being covered up since it is the only concern that both Chinese and Western virologists could plausibly share.

If you doubt the Western scientists are motivated to support a natural spillover event do read the section of this paper that discusses it in detail. And then remember what I've been saying since the beginning of this thread that there has been a concerted effort to portray the lab leak origin as a CT. It is not a CT.


Moving on: But if we aren't going to get evidence from the earliest cases in Wuhan that the Chinese have, is there another way to get at the truth? Turns out there is.

Quote:

Until recently, the COVID-19 origin question was therefore set to devolve into a simple two-way tug-of-war between the Gao club in the East and the Fauci club in the West. What none of them expected, however, was that a novel phylogenetic method would emerge capable of discrediting their careful calculus.

Mutational Order Analysis

This is where I'm going to stop and finish the discussion in a second post since my long posts tend to get ignored and dismissed as data dumps. But by all means feel free to read ahead in the paper. You won't be disappointed.

[Skeptic Ginger]

It figures. Strong evidence of a lab leak origin and people are no longer interested as evidenced by the fact no new views are noted for the thread. Have you all taken your spillover origin biases and gone home? After all, Worobey's poorly supported hypothesis sounded so convincing.

It's interesting how little notice was paid to Kumar's published work from a year ago. I'll have to go back through the thread to see what I had to say about it. I think it's because the implications of the lab leak are not mentioned in the Kumar paper, just that the first cases could have been as early Sept 2019, something I did post about.

Kumar, et al; 2921: An Evolutionary Portrait of the Progenitor SARS-CoV-2 and Its Dominant Offshoots in COVID-19 Pandemic

Quote:

Abstract
Global sequencing of genomes of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has continued to reveal new genetic variants that are the key to unraveling its early evolutionary history and tracking its global spread over time. Here we present the heretofore cryptic mutational history and spatiotemporal dynamics of SARS-CoV-2 from an analysis of thousands of high-quality genomes. We report the likely most recent common ancestor of SARS-CoV-2, reconstructed through a novel application and advancement of computational methods initially developed to infer the mutational history of tumor cells in a patient. This progenitor genome differs from genomes of the first coronaviruses sampled in China by three variants, implying that none of the earliest patients represent the index case or gave rise to all the human infections. However, multiple coronavirus infections in China and the United States harbored the progenitor genetic fingerprint in January 2020 and later, suggesting that the progenitor was spreading worldwide months before and after the first reported cases of COVID-19 in China. Mutations of the progenitor and its offshoots have produced many dominant coronavirus strains that have spread episodically over time. Fingerprinting based on common mutations reveals that the same coronavirus lineage has dominated North America for most of the pandemic in 2020. There have been multiple replacements of predominant coronavirus strains in Europe and Asia as well as continued presence of multiple high-frequency strains in Asia and North America. We have developed a continually updating dashboard of global evolution and spatiotemporal trends of SARS-CoV-2 spread (http://sars2evo.datamonkey.org/).

From the link in my last post:

Quote:

Mutational Order Analysis
Recently, a different method has been applied to the SARS-CoV-2 origin question (Kumar et al., 2021). This method is new to virology but it is widely used in cancer research (e.g. Miura et al., 2018). Using it, Kumar, Pond, and colleagues were able to infer the existence of viral strains that are older (i.e. ancestors of) Wuhan-hu-1 (the standard SARS-CoV-2 reference genome) and the other market sequences by at least 3 mutations, which is a lot.

Their innovative method is called Mutational Order Analysis (MOA). MOA is an important advance over standard approaches, not least because it doesn’t rely on clocks (i.e. time) to orient (i.e. bias) the evolutionary trees it produces. Rather, it uses genome sequence data alone to deduce the progenitor virus. Thus, MOA can be used to undo known biases, such as clocks, other sampling confounders, or even systematic sample destruction.

MOA identifies a single root virus with lineage B descending from lineage A. That was noted in citations earlier in this thread but glossed over. And some virologists argued about A preceding B.

Quote:

The virus identified by MOA as the root is separated by multiple mutations from any of the viral genomes found at the Huanan market and from Wuhan-hu-1. This infers that all known market samples are well downstream of patient zero. Therefore too, as was also concluded by Gao et al., the market samples represent an amplifying event, at most.

So what is new now?

Quote:

Very recently, Kumar and colleagues released a further preprint (Caraballo-Ortiz et al., 2022). It uses even more data (1 million genomes) and an improved method, which they call TopHap, to make their findings still more robust. The addition of many more genome sequences, including some very close to the root, affirms the original conclusions of a single root virus and that lineage B evolved from lineage A. It also allowed them to move back the root virus by one further mutation and this pushes back even further in time the predicted date of SARS-CoV-2 emergence–into September, 2019.

More pieces fall into place like the Chinese government removing public access to the SARS CoV data bases from public view back in Sept. They may very well have been aware of the COVID outbreak back then and maybe had hopes of ending it before it went beyond Wuhan.

I find it unlikely that Shi's story of rushing back to Wuhan in December to check the genomes in the WIV lab is true. Even if the leak was from the CCDC lab and not the WIV lab, she had to have known about the first cases back in September. Unless that is she believed the story the databases were taken offline to protect them from a cyber attack. Subsequent actions limiting even legit scientific inquiry about the database is evidence she knew the real reason was to hide the implications of a closely related COVID genome in the data.

I'm pausing here to read the Kumar study from March 2022 and again to break up my long post. The article in the Independent Science News is very long, very detailed and makes a strong case for the lab-leak origin. I encourage people to read it for yourselves.

[angrysoba]

Hi SG, not seen these posts until now. It is late on a Sunday here, and you posted sometime on Saturday my time, so....

Quote:

It figures. Strong evidence of a lab leak origin and people are no longer interested as evidenced by the fact no new views are noted for the thread.

...so maybe you are jumping to conclusions.

Maybe the reason why I have not been searching avidly for Origins of Covid posts appearing months after the one is not because everyone has gone coy because of "strong evidence of a lab leak", but because I haven't noticed the posts and don't have time to read through the articles and respond to each point.

I'll just make a few points...

Quote:

Indeed, Ian Lipkin, an epidemiologist at Columbia University, told an interviewer he knew of an outbreak in Wuhan by December 15th, 2019. Lipkin has subsequently confirmed this statement.

I'd be interested to know more about what Ian Lipkin was told. I assume it should not be that difficult for interviewers and scientists to give him a proper interview and find out what he knows/knew.

Quote:

And in spring 2020, Peter Daszak, President of the EcoHealth Alliance, Marjorie Pollack, an epidemiologist who runs ProMED, and Public Health Professor Lawrence Gostin made similar statements to the LA Times.

"Similar statements"? I looked at the LA Times source:

Quote:

It began for Peter Daszak, a British American scientist, a couple of days after Christmas. While the rest of the world trundled along, the president of the New York-based EcoHealth Alliance was in his office in lower Manhattan, picking up the first clues of something amiss.

Weibo, China’s Twitter, carried the warning signals: An odd illness in the city of Wuhan. Patients in respiratory distress. Some developing pneumonia. A few dying, or so said the reports, unconfirmed. Most of the sick had worked in, or visited, a “wet” market in the central Chinese city, where live fish, crabs and livestock are sold, gill-by-jowl, alongside more exotic fare, such as snakes, hedgehogs and bamboo rats.

An ebullient zoologist and parasitologist, Daszak had associates around the globe in the One Health movement — the professional community trying to prevent the spread of disease between the animal and human worlds. But, as New Year’s approached, his colleagues in China suddenly went mum.

Huh? Daszak says he heard about it a few days after Christmas. That's not unusual at all and not really similar to what Lipkin said, and interesting that this early post points out the Weibo posts about people being sick from the market.

This one is more similar:

Quote:

In mid-December, Lawrence Gostin, a professor of global health law at Georgetown Law, had a guest over to dinner. “I just heard from a friend in Wuhan that there is a novel coronavirus, and it looks very serious,” Gostin remembered saying. “He just said, ‘Pass the biscuits.’ ”

And then...

Quote:

On Dec. 30, Marjorie Pollack and her husband had just finished dinner at their weekend home on the far end of Long Island. About 9 p.m., the physician-epidemiologist checked her email and found a Weibo alert. It included what looked like a photograph of an urgent notice from Wuhan’s Municipal Health Committee about several cases of pneumonia, of unknown cause.

I don't understand what is odd about this one.

The paper you are citing suggests that this shows something untoward.

Then this...

Quote:

Early wide spread of the virus in Wuhan is evidenced too by a detailed case study of a family from Guangdong who visited Wuhan between December 29th and January 4th, 2020. Five from a total of six family members contracted COVID-19 while in Wuhan, without them having visited any markets

So what? Did they visit the Wuhan Institute of Virology? The answer is no, right? So how does it rule out the market as an origin if we have reports of people having the virus back in early December? Indeed, we know it was circulating in late 2019. That is why it is Covid-19 and not Covid-20.

____________

Anyway, I am not going to only confine myself to that.

I will read the rest and also about Mutational Order Analysis which seems interesting, and get back to you when I am not too busy.

[Skeptic Ginger]

Oh yay, I can address your comments before I post the next installment. Give me a few hours.

[Skeptic Ginger]

Originally Posted by angrysoba

Hi SG, not seen these posts until now. It is late on a Sunday here, and you posted sometime on Saturday my time, so....

...so maybe you are jumping to conclusions.

But you aren't the only one. No new views of the thread occurred until today either.

Originally Posted by angrysoba

I'd be interested to know more about what Ian Lipkin was told. I assume it should not be that difficult for interviewers and scientists to give him a proper interview and find out what he knows/knew.

"Similar statements"? I looked at the LA Times source:

Huh? Daszak says he heard about it a few days after Christmas. That's not unusual at all and not really similar to what Lipkin said, and interesting that this early post points out the Weibo posts about people being sick from the market.

You don't think 10 days apart are "similar"? Weren't the market cases at the end of Dec?

From the new article:

Quote:

For example, according to the WHO COVID origin investigation, there were 174 COVID-19 hospitalisations in Wuhan by December 31st 2019. Given the normal delay between infection and hospitalisation and the significant rate at which COVID-19 gives asymptomatic and mild cases, these hospitalisations likely represented only the tip of a large infectious outbreak in December.

Do you recall earlier in the thread the Weibo conversations about what symptoms people were searching for, the crowded hospital parking lot, and the US embassy report on the 3 Nov cases were discussed pushing the earliest cases back at least to Nov? All of that evidence was ignored and/or dismissed. But here it is coming back into the picture.

Originally Posted by angrysoba

This one is more similar:

And then...

I don't understand what is odd about this one.

The paper you are citing suggests that this shows something untoward.

It's one piece of evidence that the initial outbreak was much earlier than the Chinese are admitting to. And that corroborates the MOA findings.

Originally Posted by angrysoba

Then this...

So what? Did they visit the Wuhan Institute of Virology? The answer is no, right? So how does it rule out the market as an origin if we have reports of people having the virus back in early December? Indeed, we know it was circulating in late 2019. That is why it is Covid-19 and not Covid-20.

Why would they need to have visited the WIV?

There's a problem with the Dec cases being the first cases and that is what the market origin hypothesis depends on.

The problem of the market origin story is the cases documented there were not the first cases. We've known that since the beginning of this thread though the myth keeps being repeated in news reports. The CCDC confirms that and they have the earlier data. I don't understand why Worobey wanted to origin to be at the market so badly that he ignored the holes in his data. And why did Worobey ignore the earlier paper on MAO?

I did find it interesting that the new article's discussion of bad science by good scientists explained a lot of the bias toward the natural spillover. I've seen that since the beginning of this thread, especially in the accusations I'm promoting a CT. I stand by my initial posts and don't find the spillover evidence outweighs the lab leak evidence at all. The lab leak evidence continues to trickle in while no animal source for the spillover hypothesis has yet to be found.

The CCDC wants to blame it on Italy where some of the earliest cases occurred. What the new analysis shows is the cases spread to Italy from Wuhan very early on.


I have a few chores and some Mother's Day company coming so I'll get to the findings of the MOA study in another few hours. It's pretty convincing.

I repeat this quote:

Quote:

And we can surmise it is a lab leak that is being covered up since it is the only concern that both Chinese and Western virologists could plausibly share.

Keep in mind the authors don't suggest the Western virologists are consciously covering up the lab leak hypothesis. They explain the issue is confirmation bias, not willful coverup.

[angrysoba]

Originally Posted by Skeptic Ginger

But you aren't the only one. No new views of the thread occurred until today either.


You don't think 10 days apart are "similar"? Weren't the market cases at the end of Dec?

Many of them were at the end, but some of them were earlier. According to this timeline, a case from 10th December had been exposed, and on 15th December two more cases had been.

The first to have Covid-like symptoms is reported from 1st December.

There seem to be suspected or speculated cases stretching furhter back than that, but I don't know how reliable that information is.

Originally Posted by Skeptic Ginger

Why would they need to have visited the WIV?

There's a problem with the Dec cases being the first cases and that is what the market origin hypothesis depends on.

I don't think it does. If you make the claim that any recorded "first case" MUST be from the Huanan market or the market gets ruled out, but you are not making the same claim for the WIV then you are putting a higher bar of required evidence for the market than for the WIV.

The point is we absolutely know for certain that Covid-19 was circulating in and around the wet market. This is indisputable. All that is in doubt is whether people infected earlier than known cases are the actual first cases or whether they may have been infected via asymptomatic spread from people who had been to the market.

On the other hand, some people don't need to have any known cases from the WIV to assert its origin there.

Originally Posted by Skeptic Ginger

The problem of the market origin story is the cases documented there were not the first cases.

They are three of the first six known cases. We don't exactly know the first cases.

[Skeptic Ginger]

Originally Posted by angrysoba

Many of them were at the end, but some of them were earlier. According to this timeline, a case from 10th December had been exposed, and on 15th December two more cases had been.

The first to have Covid-like symptoms is reported from 1st December.

There seem to be suspected or speculated cases stretching furhter back than that, but I don't know how reliable that information is.

Note "is reported". It's clear from multiple pieces of evidence that cases go back further than Dec. That's pretty well documented earlier in this thread.

Given Kumar's analysis there's no reason to rehash that evidence.

Originally Posted by angrysoba

I don't think it does. If you make the claim that any recorded "first case" MUST be from the Huanan market or the market gets ruled out, but you are not making the same claim for the WIV then you are putting a higher bar of required evidence for the market than for the WIV.

Yeah, no. It was accepted the market outbreak was a super-spreader event. That was the case until Worobey claimed the market was the origin and that 2 spillovers occurred.

It's time to move on to the Kumar et al study.

Originally Posted by angrysoba

The point is we absolutely know for certain that Covid-19 was circulating in and around the wet market. This is indisputable. All that is in doubt is whether people infected earlier than known cases are the actual first cases or whether they may have been infected via asymptomatic spread from people who had been to the market.

On the other hand, some people don't need to have any known cases from the WIV to assert its origin there.

This is a straw man. It's not that one has to find the actual patient zero, the issue is no animal source or trail leading to the market, or outbreaks anywhere else in China, have been found.

Originally Posted by angrysoba

They are three of the first six known cases. We don't exactly know the first cases.

They were not 3 of the first 6 cases. According to Kumar, et al, the evidence is there that a wider outbreak occurred much earlier, in Sept or Oct.

But even without the new analysis, we already knew there were cases before the market super-spreader event. We've discussed this in the thread. Some of those earlier cases had no connection to the market. It was asserted that those cases were exposed at a different wet market and the WHO reports were cited as evidence. I said multiple times the WHO reports did not support those claims and no one in this thread could quote anything from the WHO reports that did.

Worobey relies on patient zero being a vendor at the market. He ignores the problem there were more cases earlier that the Chinese government is not coming clean about.

[W.D.Clinger]

It took me a few minutes to figure out what the two main publications Skeptic Ginger wants us to read have to do with each other. Considering those two publications in order of their publication, which is the reverse of the order in which Skeptic Ginger brought them to our attention:

Sudhir Kumar et al. An Evolutionary Portrait of the Progenitor SARS-CoV-2 and Its Dominant Offshoots in COVID-19 Pandemic. Molecular Biology and Evolution, Volume 38, Issue 8, August 2021, Pages 3046–3059, https://doi.org/10.1093/molbev/msab118

That paper is also said to have been published 04 May 2021, which I assume to have been a preprint because the journal version is dated August 2021.

The Kumar etc paper uses "a novel application and advancement of computational methods" to "report the likely most recent common ancestor of SARS-CoV-2", which they abbreviate as MRCA. From the paper:

Originally Posted by Kumar et al

MRCA is the progenitor of all human SARS-CoV-2 infections (proCoV2), which descended from the parental lineage after its divergence from its closest relatives, including bats and pangolins. We estimate that proCoV2 existed 5.8–8.1 weeks before December 24, 2019 sampling date of Wuhan-1....

These facts support the inference that coronaviruses lacking α variants were the ancestors of Wuhan-1 and other genomes sampled in December 2019 in China (fig. 1c). Therefore, we conclude that Wuhan-1 was not the direct ancestor of all the early coronavirus infections globally.

So Kumar et al think the early coronavirus infections of humans began sometime between late October 2019 and mid-November 2019, caused by their postulated virus proCoV2, which differed in certain specific aspects from the Wuhan-1 virus.

The other paper Skeptic Ginger wants us to read is considerably more controversial than the paper by Kumar et al.

Jonathan Latham and Allison Wilson. Delete, Deny, and Destroy: Chinese and Western Strategies To Erase COVID’s Origin Are Being Exposed By Independent Research. April 21, 2022.

Apart from that online publication, this paper by Latham and Wilson appears to be unpublished. (Inasmuch as Skeptic Ginger is warning us against bias in science, a glance at the web site for Independent Science News might be worth a few seconds of your time.)

Latham and Wilson cite the Kumar et al paper cited above, along with a preprint of what is now a journal paper by Marcos A Caraballo-Ortiz et al. of which Kumar was a co-author, to argue against the conclusion, drawn by Worobey et al and various others (but denied by Gao), that The Huanan market was the epicenter of SARS-CoV-2 emergence.

Because neither Kumar et al nor Caraballo-Ortiz et al so much as mention the Huanan market, Latham and Wilson deserve all of the credit for their argument against Worobey's conclusion.

Latham and Wilson go on to draw the following conclusions, which are rather more controversial:

Originally Posted by Latham and Wilson

Preadaptation of SARS-CoV-2 implies a lab leak. But it also implies a leak of a specific kind of virus; one that is not merely adapted to human cells but to transmission between whole, intact, humans. Only one theory of how SARS-CoV-2 arose fits this description. It is the Mojiang Miners Passage theory.

The Mojiang Miners Passage theory is Latham and Wilson's pet theory for the origin of SARS-CoV-2:

Jonathan Latham and Allison Wilson. A Proposed Origin for SARS-CoV-2 and the COVID-19 Pandemic. July 15, 2020.

In that online article, which appears to be otherwise unpublished, Latham and Wilson argue that some bat virus (such as RaTG13) evolved rapidly during the spring of 2012 while inside the lungs of six miners who "contracted a mysterious illness" after working in a mine at Mojiang.

That incident at Mojiang should be familiar to those who have read Skeptic Ginger's contributions to this thread. Here are a few papers that have discussed that incident in connection with SARS-CoV-2.

M. Rahalkar and R. Bahulikar. Lethal Pneumonia Cases in Mojiang Miners (2012) and the Mineshaft Could Provide Important Clues to the Origin of SARS-CoV-2. frontiers in Public Health. PERSPECTIVE published: 20 October 2020 doi:10.3389/fpubh.2020.581569

(The "PERSPECTIVE" annotation probably means the open-access journal does not regard the article as an ordinary research article.)

Alex C Speciale. Commentary: Lethal Pneumonia Cases in Mojiang Miners (2012) and the Mineshaft Could Provide Important Clues to the Origin of SARS-CoV-2. frontiers in Public Health. GENERAL COMMENTARY published: 13 July 2021 doi:10.3389/fpubh.2021.702199

(The "GENERAL COMMENTARY" annotation probably means the open-access journal does not regard the article as an ordinary research article. Alex C Speciale identifies himself as an independent researcher.)

Roger Frutos, Emilie Javelle, Celine Barberot, Herve Tissot-Dupont, and Christian A Devaux. Origin of COVID-19: Dismissing the Mojiang mine theory and the laboratory accident narrative. Environmental Research 204 (2022) 112141. Available online 28 September 2021. https://doi.org/10.1016/j.envres.2021.112141

That paper appears to be an ordinary research article, accepted two months after its submission to the journal. Frutos et al do not think much of the two articles cited immediately above theirs. This is their entire abstract:

Originally Posted by Frutos et al

The origin of SARS-CoV-2 is still the subject of a controversial debate. The natural origin theory is confronted to the laboratory leak theory. The latter is composite and comprises contradictory theories, one being the leak of a naturally occurring virus and the other the leak of a genetically engineered virus. The laboratory leak theory is essentially based on a publication by Rahalkar and Bahulikar in 2020 linking SARS-CoV-2 to the Mojiang mine incident in 2012 during which six miners fell sick and three died. We analyzed the clinical reports. The diagnosis is not that of COVID-19 or SARS. SARS-CoV-2 was not present in the Mojiang mine. We also bring arguments against the laboratory leak narrative.

There are, however, people who take Latham and Wilson's Mojiang Miners Passage theory seriously. I suspect Skeptic Ginger will continue to bring their opinions to our attention.

[angrysoba]

Originally Posted by Skeptic Ginger

Worobey relies on patient zero being a vendor at the market. He ignores the problem there were more cases earlier that the Chinese government is not coming clean about.

No, he does not.

This is from Worobey:

Quote:

the earliest known cases should not necessarily be expected to be the first infected or linked to Huanan Market: They probably postdated the outbreak’s index case by a considerable period (10). Moreover, only ∼7% of SARS-CoV-2 infections lead to hospitalization (11); most fly under the radar. Similarly, it is entirely expected that early, ascertained cases from a seafood market would be workers who were not necessarily directly associated with wildlife sales once the outbreak began spreading from human to human. The index case was most likely one of the ∼93% who never required hospitalization and indeed could have been any of hundreds of workers who had even brief contact with infected live mammals.

Link

I am pretty sure we have been over this many times.

Worobey does NOT claim the first case has been identified.

This is very important because if you do not understand this, you do not understand what Worobey et al. is claiming.

[Capsid]

Thanks for the information SG. Interesting reads. I got focused on the miners' theory which seems to hinge around the samples sent to WIV, particularly the thymus sample from one of the miners. Is there documented evidence that thymus samples were sent to Zheng-li Shi? The thymus samples are important here because this could be the source of the virus (assuming that the recombination of viruses within the miners lead to SARS-COV-2). SARS-COV-2 does not cause viraemia so the blood samples sent to WIV would not likely be the source. But timing is critical, there's a big gap between samples sent to WIV and COVID outbreak. Also, I struggle with the infected lab worker causing an outbreak in the wet market some 20km away. Thinking of those distances in my own city, London, UK, that would equate to a lab in North London (there is one in Colindale) seeding an outbreak in South London.

[Skeptic Ginger]

Originally Posted by Capsid

Thanks for the information SG. Interesting reads. I got focused on the miners' theory which seems to hinge around the samples sent to WIV, particularly the thymus sample from one of the miners. Is there documented evidence that thymus samples were sent to Zheng-li Shi? The thymus samples are important here because this could be the source of the virus (assuming that the recombination of viruses within the miners lead to SARS-COV-2). SARS-COV-2 does not cause viraemia so the blood samples sent to WIV would not likely be the source. But timing is critical, there's a big gap between samples sent to WIV and COVID outbreak. Also, I struggle with the infected lab worker causing an outbreak in the wet market some 20km away. Thinking of those distances in my own city, London, UK, that would equate to a lab in North London (there is one in Colindale) seeding an outbreak in South London.

There are 2 potential sources for the WIV to have had a closely related SARS CoV before the pandemic. They've been posted in this thread.

A lot has been posted about the 2012 outbreak of a viral infection in the Yunnan miners. The specimens were sent to more than just the WIV and none of those specimens have really been accounted for. IIRC there's a link here to testing that didn't reveal direct evidence. I believe that was one of your objections asking which specific antibody tests were done.* Those specimens which were in a number of labs deciphering the genomes were reportedly ordered destroyed by the Chinese government. I may have some of these details wrong or conflated but they can be found in the thread.


There's another possibility and that is an email which revealed Daszak's group sent specimens from the Laos caves to the WIV. Here's a quick reference:

Months before the Covid-19 outbreak occurred, scientists at the infamous Wuhan lab in China were studying coronaviruses found in bats from Laos, according to new evidence

Quote:

However, new leaked emails between EcoHealth Alliance -- the US-based nonprofit that helped fund some research at WIV -- and the US government funders reveal that viral DNA from "bats and other high-risk species" were sent to Wuhan between June 2017 and May 2019, the report said.

The emails were unearthed by a Freedom of Information request made by a US-based campaign group called White Coat Waste Project.

Besides working in Laos, EcoHealth Alliance also investigated cave bat viruses in Yunnan, China, and sent the samples to scientists in Wuhan for further study, the report said.

We don't really know about all the viral genomes contained in the samples. We do know:

Quote:

However, records of the genetic sequences collected from both Yunnan and Laos were removed from an online database at the Wuhan institute in September 2019, just months before the pandemic struck the world, making it difficult for the experts searching the origins of the pandemic.

And that brings the new phylogenetic study full circle to some things discussed earlier in the thread. From the new research:

Quote:

Very recently, Kumar and colleagues released a further preprint (Caraballo-Ortiz et al., 2022). It uses even more data (1 million genomes) and an improved method, which they call TopHap, to make their findings still more robust. The addition of many more genome sequences, including some very close to the root, affirms the original conclusions of a single root virus and that lineage B evolved from lineage A. It also allowed them to move back the root virus by one further mutation and this pushes back even further in time the predicted date of SARS-CoV-2 emergence–into September, 2019.

This September spillover date further contradicts Pekar and Worobey’s date. However, it agrees well with a broad set of other phylogenetic analyses and makes the farflung virus findings in Europe and elsewhere more plausible still (Mostefai et al., 2021; Schrago and Barzilai, 2021; Song et al., 2021; Xia, 2021).

Finding 2 lineages, A & B, in the early genomes was not evidence of 2 separate spillover events. And from recent discussions in the thread the virus was adapted to human spread and became even more so when it acquired the furin cleavage site, not something found in any of the closely related horseshoe bat SARS CoVs. Again IIRC you or someone else posted, "not the furin cleavage site again."*

I'll hunt down the citation and post it next supporting the conclusion the furin cleavage site didn't likely evolve in the bat viruses because it offered no advantage to SARS CoVs infecting horseshoe bats. Of course it might have been randomly acquired in a recombination event, but then it would still have to have been retained and with no advantage to the virus circulating in bats, one would think it might not have been.


So the evidence supports the conclusion that regardless of the source of the specimens either the CCDC and/or the WIV were working with, they were well adapted to spilling over into the human population but became even more so when the furin cleavage site was acquired.


The CCDC was closer to the seafood market and they moved their lab to a nearby site shortly before the pandemic was recognized to be spreading worldwide. And even though these viruses should have been considered PPVs (potentially pandemic viruses), both labs, the WIV and the CCDC, worked on SARS CoVs under level 2 biosecurity.


But if the virus was circulating more widely back in October (recognized in Sept), it's a moot point how close the potential initial source was to the seafood market. And there were documented cases before the super-spreader event at the market anyway. We just don't have the case details or the genome analysis like we do with the market cases.



*Don't get me wrong, your challenges were fine and actually helpful. I only bring them up now because they are relevant to looking at past discussions in the thread.

[Skeptic Ginger]

Lancet Sep 2021: SARS-CoV-2 spike and its adaptable furin cleavage site

Quote:

For coronaviruses, furin cleavage sites at the interface of the S1 and S2 domain are not unusual, being found widely in betacoronaviruses in the embeco lineage (which are considered to be of rodent origin) as well as in avian-origin gammacoronaviruses and certain feline and canine alphacoronaviruses (with an unknown origin). Furin cleavage sites are also found in certain bat-origin MERS-like merbecovirises, but not—with the exception of SARS-CoV-2—in the sarbecovirus lineage. The presence of a furin cleavage motif at the SARS-CoV-2 S1–S2 interface is therefore highly unusual

With the caveat not enough SARS CoVs have been sampled:

Quote:

Whittaker recently (August 2021) published a comment describing the SARS-CoV-2 FCS as “highly unusual” (Whittaker 2021). Similar studies on MERS-CoV had also determined that its S1/S2 FCS is required for efficient entry into human lung and intestine cells, and influences the cell tropism of the virus (Park et al. 2016; Kleine-Weber et al. 2018). In September 2021, it was reported that an international group of scientists (including from the Wuhan Institute of Virology) had, in March 2018, proposed a roadmap for detecting novel proteolytic cleavage sites (including FCSs) in the spike sequences of novel sarbecoviruses and inserting these novel cleavage sites into the appropriate parental strain (Daszak 2018; Lerner and Hibbett 2021). These research endeavors and others described in our introduction relating to the S1/S2 FCS in the context of various CoV spikes have led to speculation that the SARS-CoV-2 FCS could have been similarly inserted to characterize its function in different cell types. The virologist David Baltimore commented that “these features make a powerful challenge to the idea of a natural origin for SARS2,” later clarifying that “you can't distinguish between the two origins from just looking at the sequence” (Caltech Weekly 2021). ...

FCSs have evolved naturally in other non-sarbecovirus families of betacoronaviruses (Wu and Zhao 2020). Therefore, an S1/S2 FCS emerging in a sarbecovirus is consistent with natural evolution. Even so, the knowledge that scientists had a workflow for identifying novel cleavage sites in diverse SARSr-CoVs and experimentally characterizing these cleavage sites in SARSr-CoVs—likely in a manner that makes the resulting recombinant SARSr-CoV practically indistinguishable from a rare SARSr-CoV with a naturally emerging FCS—makes it challenging to rule out an artificial origin of the SARS-CoV-2 S1/S2 FCS (Daszak 2018; Lerner and Hibbett 2021).

Not the article I was looking for but the relevant information is still here.


I'll move on but still post the article I was looking for if I find it.

[Skeptic Ginger]

Some of this post includes quotes I used above. This material is from 3 papers so don't be accusing me of a data dump just because there is a lot of important information in the papers.

Here's the more recent paper the Independent Science News refers to. The paper refers to the TopHap technique which is an updated version of the MOA.

Quote:

We have shown that the TopHap phylogeny for common variants and haplotypes in the 68KG SARS-CoV-2 dataset works well and agrees with the mutation tree produced using MOA (Kumar et al., 2021). But, the TopHap approach offers some advantages over MOA. Firstly, MOA assumes the sequencing error rate to be constant throughout the outbreak, which is unlikely to hold for pathogenomic datasets acquired in different laboratories at different times.

Secondly, MOA analysis needs to have mutant bases indicated at the outset, a limitation addressed by Kumar et al. (2021), but at a large computational expense. In contrast, TopHap analyses directly use outgroup in standard phylogenetic analysis. TopHap analysis is certainly more computationally efficient as the analysis of the 68KG dataset took only a few hours. In contrast, MOA took more than a week to compute.

Other results are cited that corroborate the findings in the TopHap analysis.

Mar 2022: TopHap: rapid inference of key phylogenetic structures from common haplotypes in large genome collections with limited diversity

Quote:

... we set out to develop a method for building the phylogenetic tree of genomic haplotypes consisting of positions harboring common variants to improve the signal-to-noise ratio for more accurate and fast phylogenetic inference of resolvable phylogenetic features. ...

An application of TopHap to more than 1 million SARS-CoV-2 genomes reconstructed the most comprehensive evolutionary relationships of major variants, which confirmed the 68KG phylogeny and provided evolutionary origins of major and recent variants of concern.

The results take the MRCA back another month or so from the 2021 analysis:

Quote:

With a mutation rate range of 6.64 × 10−4 to 9.27 × 10−4 substitutions per site per year (Pekar et al., 2021), we can estimate that proCoV2 existed 7.7–10.8 weeks before the December 24, 2019 sampling date of Wuhan-1. This places the progenitor of SARS-CoV-2 to have evolved in mid-September to early-October 2019, many weeks earlier than the mid-November 2019 date proposed by Pekar et al. (2021). ...

And the initial paper from 2021: An Evolutionary Portrait of the Progenitor SARS-CoV-2 and Its Dominant Offshoots in COVID-19 Pandemic

Quote:

We report the likely most recent common ancestor of SARS-CoV-2, reconstructed through a novel application and advancement of computational methods initially developed to infer the mutational history of tumor cells in a patient. This progenitor genome differs from genomes of the first coronaviruses sampled in China by three variants, implying that none of the earliest patients represent the index case or gave rise to all the human infections. However, multiple coronavirus infections in China and the United States harbored the progenitor genetic fingerprint in January 2020 and later, suggesting that the progenitor was spreading worldwide months before and after the first reported cases of COVID-19 in China. ...

In particular, the root of the SARS-CoV-2 phylogeny remains elusive (Morel et al. 2021; Pipes et al. 2021) because the closely related nonhuman coronavirus (outgroups) are more than 1,100 base differences from human SARS-CoV-2 genomes, as compared with fewer than 30 differences between human SARS-CoV-2 genomes’ sequenced early on (December 2019 and January 2020)

So the MOA technique was adapted from a model used to infer the mutational history of tumor cells. The details of the analysis are described in this paper.


Ready to spread in humans right out of the gate:

Quote:

These spatiotemporal patterns suggest that proCoV2 already possessed the repertoire of protein sequences needed to infect, spread, and persist in the global human population

Now to the Independent Science News analysis:

One source:

Quote:

A single root virus means the pandemic began with only one initial spillover. A single spillover event is a crucial observation because it strongly implies a lab leak* (since scientists tend to work with pure cultures); whereas equivalent evidence for multiple and/or genetically diverse spillovers would have implied a natural source. MOA also shows that all lineage B viruses are descended from one lineage A virus.

*Implies a lab leak when added to other evidence like being ready out of the box and lack of animal trail.


More pieces fit together:

Quote:

Very recently, Kumar and colleagues released a further preprint (Caraballo-Ortiz et al., 2022). It uses even more data (1 million genomes) and an improved method, which they call TopHap, to make their findings still more robust. The addition of many more genome sequences, including some very close to the root, affirms the original conclusions of a single root virus and that lineage B evolved from lineage A. It also allowed them to move back the root virus by one further mutation and this pushes back even further in time the predicted date of SARS-CoV-2 emergence–into September, 2019.

This September spillover date further contradicts Pekar and Worobey’s date. However, it agrees well with a broad set of other phylogenetic analyses and makes the farflung virus findings in Europe and elsewhere more plausible still (Mostefai et al., 2021; Schrago and Barzilai, 2021; Song et al., 2021; Xia, 2021).

Sorry to pick on Worobey but I found his analysis annoying for reasons I posted earlier.


And the location of the initial event was Wuhan, not Italy.

Quote:

Although MOA supports the market being a secondary site, it contradicts the idea of a virus origin outside China. Gao at al. point at evidence for very early cases outside of China and imply that one of these was the ultimate source. But, it is clear from the Kumar et al. analysis that Wuhan and China are where the genetic diversity around the root occurs.

Summarizing the evidence:

Quote:

... that the market samples containing SARS-CoV-2 were mixed with human RNA and not with animal RNA; ...

... the lack of support for dismissing viruses intermediate between lineages A and B; the methodological superiority of the MOA method, which identifies a single and significantly earlier root; ...

... there is still no evidence for wild or farmed animals being infected with SARS-CoV-2 in China, either before, during, or since the pandemic broke out. ...

... Third, there is the unremarkable nature, by Chinese standards, of the Huanan market. Why Wuhan? It is a question still unanswered by natural zoonotic theories.

In short, it is unreasonable to claim that the Huanan market was the “unambiguous epicentre” of the pandemic (Worobey et al., 2022). Such certitude is scientifically unwarranted

Wuhan is not a wet market hub like Guangdong is. No other related outbreaks have occurred in other cities or around the bat caves. IOW, there is no trail leading to Wuhan except via potential trails to one of the research labs.

Quote:

The two MOA/TopHap papers provide by far the strongest candidate yet for a root virus and they detail its subsequent evolution (Caraballo-Ortiz et al., 2022; Kumar et al., 2021). ...

Whichever way one looks at the evidence, it is evident that even the very earliest viruses were not only highly adapted to humans but able, unaltered, to cause a pandemic. ...

It was not until the eighth mutation did [an adaptive mutation] arise (β2 in Fig. 1) that has subsequently been shown to increase the fitness of the virus in humans (Dearlove et al., 2020; van Dorp et al., 2020) β2 is the well-known D614G mutation, first identified in Wuhan late January. By this time the pandemic was well underway.

Here's where the analysis leaves out the possibility the origin could have been from the Laos caves to the WIV:

Quote:

Preadaptation of SARS-CoV-2 implies a lab leak. But it also implies a leak of a specific kind of virus; one that is not merely adapted to human cells but to transmission between whole, intact, humans. Only one theory of how SARS-CoV-2 arose fits this description. It is the Mojiang Miners Passage theory.

This was an interesting observation:

Quote:

Why, after all, did public institutions like NIH, NIAID, USAID, DOD, who have showered money on the EcoHealth Alliance, supposedly to prevent pandemics, not fund widespread searches for early SARS-CoV-2 infections at the very start of the pandemic?

Fauci was certainly defensive about the NIH funding gain of function research.


The paper ends with:

Quote:

The other necessary benchmark is an ethical one. Dr Tedros of the WHO has called investigating the origin of the pandemic “a moral obligation“. We would go further. Although there is no law against obstructing origin research, it should nevertheless be considered a crime against all humanity to make it more likely that an event that resulted in millions of deaths and untold misery will recur because we never found its cause (Relman, 2020).

And with that I'm off to look through some of the earlier posts in the thread.

[Planigale]

Originally Posted by Skeptic Ginger

So how is that evidence for a natural spillover? That doesn't make any sense.

It also doesn't address the problem those lineages might only differ because of sequencing error.

And it doesn't address the problem that the virus appeared out of the box adapted to humans. Replicating in an animal source wouldn't be expected to have produced 2 different variants both well adapted to human to human transmission and significant disease.

You do realise that this is exactly the argument for intelligent design creationists make? The eye is so suited to seeing that it must have been designed. N-CoV-2 is perfectly designed to be transmitted in humans that it must have been designed.

But what you miss are the billions of attempts the virus made to escape from 'civets' and get into humans before one was successful. Yes this one mutation worked, but that is why we know about it. What about the A strain that did not succeed in being a pandemic but died out? Are you arguing for two releases from the laboratory?

How did it spread to mink? Do we think a laboratory in Denmark engineered the virus to spread into mink? What about deer? Is this the work of Fort Bragg? Viruses can cross species and be successful. You only hear the success story.

The truth is N-CoV-2 was not particularly good at being transmitted, strain A died out, strain B did well because it was transmissible in the asymptomatic phase. As subsequent mutations have shown it can be far more transmissible than the original strain was. Even SARS was more transmissible and we know that cam straight from animals. Neither rank as compared with norovirus or measles.

Your argument that because it spread in humans it could not have originated in animals is nonsense. What pandemic viruses have ever originated in laboratories. laboratory isolates tend to become less transmissible because they grow in cell cultures with no immune defences.

[Planigale]

Originally Posted by Skeptic Ginger

This is bizarre logic.

Neither one 'spilled over' ready to go with rapid human to human spreading.

SARS certainly had better transmission from human to human than N-CoV-2 did. It was the fact that symptoms started before transmission that allowed SARS to be controlled.

[Skeptic Ginger]

Is this another one of your Poe posts?

Originally Posted by Planigale

You do realise that this is exactly the argument for intelligent design creationists make?

Oh puleese! If you want to have a serious conversation here, this nonsense is not a good start.

Quote:

The eye is so suited to seeing that it must have been designed. N-CoV-2 is perfectly designed to be transmitted in humans that it must have been designed.

No, just no. That is not the argument at all. Try again, this time look at the actual evidence starting with the way species jumps most often result in a period of time the virus takes to better adapt to the new species. It happened with SARS1 and it's why the H5N1 bird flu has spread to a few people but has yet to become a virus easily transmitted person to person.

Quote:

But what you miss are the billions of attempts the virus made to escape from 'civets' and get into humans before one was successful. Yes this one mutation worked, but that is why we know about it. What about the A strain that did not succeed in being a pandemic but died out? Are you arguing for two releases from the laboratory?

How did it spread to mink? Do we think a laboratory in Denmark engineered the virus to spread into mink? What about deer? Is this the work of Fort Bragg? Viruses can cross species and be successful. You only hear the success story.

The truth is N-CoV-2 was not particularly good at being transmitted, strain A died out, strain B did well because it was transmissible in the asymptomatic phase. As subsequent mutations have shown it can be far more transmissible than the original strain was. Even SARS was more transmissible and we know that cam straight from animals. Neither rank as compared with norovirus or measles.

Your argument that because it spread in humans it could not have originated in animals is nonsense. What pandemic viruses have ever originated in laboratories. laboratory isolates tend to become less transmissible because they grow in cell cultures with no immune defences.

You're not even keeping up in the thread. Try again.

[Skeptic Ginger]

Originally Posted by Planigale

SARS certainly had better transmission from human to human than N-CoV-2 did. It was the fact that symptoms started before transmission that allowed SARS to be controlled.

More not keeping up in the thread and not keeping up on the difference between SARS 1, no mild cases, and SARS 2, lots of mild and asymptomatic cases.

It's not that symptoms started before transmission with SARS 1. Had that been the case it wouldn't have spread as far as it did. It's that cases could be found and contact tracing with subsequent isolation allowed us to stop transmission.

[angrysoba]

Originally Posted by Skeptic Ginger

It happened with SARS1 and it's why the H5N1 bird flu has spread to a few people but has yet to become a virus easily transmitted person to person.

The problem with this argument is that it is self-defeating.

SARS-2 cannot be natural because SARS-1 took longer to become transmissable from human to human could be used to show that SARS-1 is not natural.

You could similarly argue that SARS-1 could not be natural because it hasn't taken as long to become transmissable from human to human as H5N1.

All we can really say is that SARS-2 appears to have become human-to-human transmissable quickly, just as SARS-1 was, but maybe even quicker.

[Skeptic Ginger]

Originally Posted by angrysoba

The problem with this argument is that it is self-defeating.

SARS-2 cannot be natural because SARS-1 took longer to become transmissable from human to human could be used to show that SARS-1 is not natural.

You could similarly argue that SARS-1 could not be natural because it hasn't taken as long to become transmissable from human to human as H5N1.

All we can really say is that SARS-2 appears to have become human-to-human transmissable quickly, just as SARS-1 was, but maybe even quicker.

You're doing the same thing you've done in the past, cherry picking a bit here and a bit there without addressing the totality of the evidence.

If SARS CoV2 was the result of a natural spillover event one needs to explain why it appeared suddenly in one market in Wuhan.

From the Independent Science News:

Quote:

... Instead, they point to the nearby Huanan seafood market as the probable spillover site, even though it is similar to thousands of others in China.

A Huanan market origin has officially been dismissed by the authorities in China. Nevertheless, on February 25th a preprint authored by George Gao, head of China’s CDC, and 38 other Chinese virologists appeared that seems intended to settle the issue (Gao et al., 2022).

The Gao article concludes, based on several lines of evidence, including a lack of correlation between positive virus samples and stalls that sold animals, that the Huanan market was simply an amplifying event.

Species jumping is a complex issue that would take a page or more to get into. There's no point except to look at SARS CoV 2 specifically. There's a link way back in the thread that hypothesized with some evidence that SARS CoVs are potential generalists, crossing species more easily than some other viruses.

There again remains the issue that no ready to go precursor virus has been found, not even a close one. What the MOA/TopHap study found was that when SARS CoV 2 entered the human population, probably in Sep/Oct 2019, it did not spend any time adapting to human to human spread before spreading widely.

Directly from the recent Kumar paper:

Quote:

With a mutation rate range of 6.64 × 10−4 to 9.27 × 10−4 substitutions per site per year (Pekar et al., 2021), we can estimate that proCoV2 existed 7.7–10.8 weeks before the December 24, 2019 sampling date of Wuhan-1.

And from the 2021 paper:

Quote:

However, multiple coronavirus infections in China and the United States harbored the progenitor genetic fingerprint in January 2020 and later, suggesting that the progenitor was spreading worldwide months before and after the first reported cases of COVID-19 in China. ...

So the newest study determined the root virus turned up in Wuhan without evidence of a natural spillover event, let alone 2 such events. There was evidence posted early in this thread of a viral pneumonia spreading early on in Wuhan (full hospital parking lot and searches on Weibo for symptoms that could have been SARS CoV 2). There was no evidence in the Chinese pneumonia/influenza surveillance system of any unusual clusters of pneumonia elsewhere in China in 2019.


Find evidence of COVID in deer in China or in minks in China from 2019 or earlier. That would be worth looking at.

[angrysoba]

Originally Posted by Skeptic Ginger

You're doing the same thing you've done in the past, cherry picking a bit here and a bit there without addressing the totality of the evidence.

I'm addressing a specific argument that you have made. I think it is worth examining each one if you think it is worth making the argument.

You argue that the virus could not have been so adapted to humans in a short space of time because:

a) SARS-1 took longer
b) H5N1 has taken even longer

But by that argument, SARS-1 could not have adapted so quickly because it did so quicker than H5N1.

There is an easy answer to this point: some viruses achieve pandemic potential quicker than others by mutational chance.

Originally Posted by Skeptic Ginger

If SARS CoV2 was the result of a natural spillover event one needs to explain why it appeared suddenly in one market in Wuhan.

Sure. And one day, maybe we or someone will. But the "needs to explain why..." also applies to every other theory.

Originally Posted by Skeptic Ginger

Species jumping is a complex issue that would take a page or more to get into.

I read a whole book about it and have been following a lot of scientists talking about this. Frankly, it requires far more knowledge, and ultimately it requires the type of knowledge that I will never attain. In fact, even for the top experts, there are a LOT of areas of incomplete knowledge.

Originally Posted by Skeptic Ginger

There's no point except to look at SARS CoV 2 specifically.

Then there is no point in you comparing SARS-1 and H5N1 and drawing conclusions about how possible it was to adapt to humans so quickly.

Originally Posted by Skeptic Ginger

So the newest study determined the root virus turned up in Wuhan without evidence of a natural spillover event, let alone 2 such events.

Okay, I will have to look at that.

Originally Posted by Skeptic Ginger

There was evidence posted early in this thread of a viral pneumonia spreading early on in Wuhan (full hospital parking lot and searches on Weibo for symptoms that could have been SARS CoV 2). There was no evidence in the Chinese pneumonia/influenza surveillance system of any unusual clusters of pneumonia elsewhere in China in 2019.

So there is a bit of a contradiction here, I think.

You are expecting a viral outbreak elsewhere in the country to be easily picked up by the surveillance system.

Yet, if that is true, why did it not pick up the early (Sept-Oct) outbreak?

Worobey has an answer to that, which is that the system as set up is not sensitive enough to small numbers of cases. He also, in fact, points out that even SARS-CoV2 was not identified through this system.

If the actual pandemic itself was not detected by it, we cannot assume that the virus's precursor must be.