Thread by @michaelzlin

There have been a lot of stories recently on the search into COVID19/SARSCoV2 origins, but they have been written to tell stories of intrigue or mystery, not to summarize known facts.

Thus I thought it might be useful to succinctly summarize what we actually know...

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I'll say from the outset we know zero about where sarscov2 itself came from, so the only facts we can list are those that could be proximally relevant. That is, each of these facts is either about SARSCoV2 discovery or just one potential step removed from SARSCoV2 origins.
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First, the briefest bit of background: SARSCoV2 is in the clade or coronaviruses called the sarbecoviruses, named after its first known member, SARSCoV1, the cause of SARS discovered in 2002. SARSCoV1 and SARSCoV2 are 80% identical.

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They essentially cause the same range of pathologies (flu-like disease which then progresses sometimes to inflammatory pneumonia and sometimes systemic inflammation), but with very different outcome distributions

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Now, on to the circumstantial facts.

1. The 1st known case of SARSCoV2 disease was detected on 2019/12/8 in Wuhan, China. Most cases in the next 3 wks were linked to the Huanan seafood market, but the 1st case, and 4 of the first 5, were not.
nejm.org/doi/10.1056/ne…

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2. The closest known sarbecovirus to SARSCoV2 is RaTG13 (96%), which was isolated from a Mojiang mine in 2013 by WIV scientists. WIV scientists were alerted to the mine after 3 miners contracted a SARS-like pneumonia and died.
frontiersin.org/articles/10.33…

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3. The wild bat-resident precursor to SARSCoV2 has not yet been found but it is not RaTG13 itself, whose 96% similarity still suggests 50 years of divergence from SARSCoV2.
nature.com/articles/s4156…

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4. The first paper on RaTG13 by Shi Zhengli of WIV (2020/2, nature.com/articles/s4158…) did not discuss where RaTG13 came from; this was figured out by DRASTIC (2020/5, newsweek.com/exclusive-how-…).

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Although RaTG13 is not the wild precursor to SARSCoV2, details about where, when, and why it was isolated is relevant to SARSCoV2, as it provides a plausible path for the transport (knowing or unknowing) of SARSCoV2 to Wuhan.

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5. Zhengli Shi's group at WIV was sent serum samples from the sick miners to test for antibodies that react to SARSCoV1. The PhD thesis of Huang Canping recorded that 4 miners' sera were positive for SARSCoV1-reactive antibodies.
frontiersin.org/articles/10.33…

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6. Note antibodies raised against SARSCoV2 cross-react to SARSCoV1 and vice versa. Thus a positive reaction to SARSCoV1 antigens, if true, in the miners' serum would indicate some sort of sarbecovirus, which could have at least 20% divergence from SARSCoV1
sciencedirect.com/science/articl…

7. I verified the original statement in Huang's thesis about the miners being seropositive for sarbecovirus. Whether the miners were infected with a sarbecovirus is relevant for assessing whether it's worth attempting to find SARSCoV2 sequences in the miner serum samples.
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8. However, Zhengli Shi said in 2020.11 that the miners were seronegative for SARSCoV1 antibodies in 2012. That contradicts Huang's thesis, so only one can be correct. Shi said the sera were also negative for SARSCoV2 antibodies when retested in 2020. nature.com/articles/s4158…
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9. It is not known if the miner serum samples that yielded the 9 sarbecoviruses have since been tested to see if they contained SARSCoV2, but now we know the SARSCoV2 sequence, it would be straightforward to do the PCR.
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10. Thus whether the wild precursor to SARSCoV2 was in the Mojiang mine is unknown, regardless of whether Huang or Shi is correct. But if Huang is correct, it's worth PCRing from the miners' sera to look for it. If Shi is correct, it's not worth doing so.
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11. Shi reported obtaining sequences of 9 sarbecoviruses (including RaTG13) out of 293 coronaviruses from 1322 bat guano samples from the mine 2012-2015. Shi said next-gen sequencing in 2018 allowed recovery of more RaTG13 sequence.
nature.com/articles/s4158…
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12. Shi has not said if next-gen sequencing has now been attempted on those 1322 samples to look for SARSCoV2.
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13. Shi has not said if WIV attempted to culture those 9 sarbecoviruses. But WHO's Embarek may know: "They never succeeded to culture a virus out of the bat feces sample.” Not clear if he was speaking loosely, but this implies an attempt.
wsj.com/articles/wuhan…
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14. Besides WIV, Wuhan CDC was also involved in bat collection and virus sampling of the Mojiang mine and various caves
washingtonpost.com/world/asia_pac…
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15. Regarding a potential wildlife origin, sequencing of thousands of animal samples in and around Wuhan and in suppliers to Wuhan markets have not found SARSCoV2, per the WHO joint report 4/2021
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16. The only other sarbecovirus to have entered humans is SARSCoV1, so its transmission path is often cited as a model. It jumped from civets to humans in wildlife markets in Guangdong province, and its ultimate reservoir is believed to be bats. nejm.org/doi/10.1056/NE…
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17. However WIV1 and WIV16, the closest known bat-resident viruses to SARSCoV1 (95/95%), have the ability to infect human cells directly. So in-civet evolution was not necessary; direct bats to humans was possible too.
journals.asm.org/doi/10.1128/JV…
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18. Regarding virus engineering, Shi's lab had made chimeric sarbecoviruses by inserting newly discovered spike sequences into the WIV1 backbone, and assessing for retained ability to to infect human cells (WIV1 already had this capability).
journals.plos.org/plospathogens/…
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19. They have not reported using other backbones to perform chimeric virus work, so the above is the closest known work to "gain-of-function" studies.
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20. Cultures of WIV1 were done at BSL2 level (gloves, lab coats, eye protection and masks depending on perceived risk). The paper that describes the virus production method (and referenced by the chimeric virus paper) is
journals.asm.org/doi/10.1128/JV…
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And that's it. That's all the circumstantial facts. We have no direct facts on SARSCoV2 origins. On one hand we have facts on RaTG13 providing an example path that SARSCoV could have taken to Wuhan, and on the other the precedence of SARS1 that's non-specific to Wuhan.
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There's some negative circumstantial data: the virus-negative animal samples, and the failure to report results of easy searches for SARSCoV2 in samples in WIV's possession that a lab interested in papers or solving the mystery of the century would do.
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And now my opinion: I think BSL2 for work on WIV1 (95% identifcal to SARSCoV1) is an actual scandal, recorded in print. Shi's whole reason to study WIV1 was that it was an actual bat virus but like SARSCoV1 can replicate in human cells.
nature.com/articles/natur…
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Being 95% identical to SARSCoV1, you should just treat it the same: There is an exceedingly high likelihood it would create a deadly epidemic if it got into a human. Indeed the conclusion of her Nature paper on WIV1 is that it or something similar could be the next SARS.
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So then in their next paper they grow this virus in the lab under BSL2 conditions! BSL2 can be gloves and lab coats and not mouth pipetting, and cleaning up spills, and that's it. No masks or goggles unless you feel like it. 29/n

So while WIV workers don't seem to have gotten infections by WIV1, they may have dodged a bullet then. And it raises the question if they were performing other viral culture experiments at BSL2, experiments that may have been contaminated with SARSCoV2 without them knowing.
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"analysts note that it is plausible that researchers may have unwittingly exposed themselves to the virus without sequencing it during experiments or sampling activities, possibly resulting in asymptomatic or mild infection.”

...as I suggested in June

ft.com/content/5e20cb…

Is it more or less likely than a farmer picking it up in Yunnan then passing it on to someone traveling to Wuhan? Hard to say, but a responsible and responsive government would at least resequence everything in their sample collections and find out.

The reports did indicate the virus was unknown to Chinese authorities prior to the epidemic, which argues against engineering. This was already revealed in April, as I mentioned.

https://mobile.twitter.com/michaelzlin/status/1383642182532288520

Anyway I haven't commented on the intelligence assessment conclusions when first announced in August or when the report was released last week because they didn't add anything we didn't already know, and they didn't change my previous assessment.

The actual unclassified document doesn't provide the detailed reasoning, but you can imagine they used the same facts as I presented above to deduce their similar conclusions:

cnn.com/2021/10/29/pol…

Anyway I only got into this topic to set the record straight when virologists with conflicts of interest made unsupported statements or attacked other scientists while claiming to speak for the majority. Dislike manipulative power grabs regardless of the source.

Overall I'm more interested in sharing info that can actionably help people in vaccines and treatments, so this may be my last post on this topic for a while.

Okay just one more point, as it's a scientific one. Any complaint that resequencing existing bat samples wouldn't do anything useful would be wrong, as the whole point of Shi Zhengli's and Wuhan CDC's research was to find bat coronaviruses that can infect human cells...

then study how many mutations were needed for efficient replication. So if there's a possibility the wild predecessor to SARSCoV2 exists in their samples, they would want to find it if their previous decade of work and millions of dollars was not just meant to be research theater

With the known sequence of SARSCoV2 in hand and known regions of 100% identity with other sarbecoviruses they can design highly sensitive primers to retest their entire collection (thousands of samples). But rumors are their collections were ordered destroyed.