Today our review of the evidence for the origins of SARS-CoV-2 graduated from a pre-print to peer-reviewed pre-proof in @CellCellPress.

Can we rule out a "lab leak"? No, but if we objectively follow the evidence, it leads us away from that hypothesis.
cell.com/cell/fulltext/…
In anticipation of the inevitable bad faith threads and Medium posts that will ensue from the more conspiracy-minded in the origins world, I'll preemptively address some common questions. But please do read the entire thing:
cell.com/cell/pdf/S0092…
Let's start with the sole affirmative evidence that suggests a lab leak.

SARS-CoV-2 emerged in Wuhan. The Wuhan Institute of Virology is also in Wuhan. They study bat CoVs at WIV. SARS-CoV-2 could have been one of those viruses.

That's it. Everything else is speculative.
In fact, there's not a shred of evidence that SARS-CoV-2 or a closely related progenitor was ever at WIV.

All the speculation otherwise is basically a variation of "the Chinese government lies about some things, so let's assume they are lying about this too with zero evidence."
Zoonotic origin is a likelier explanation just based on history. Every coronavirus that previously spilled over into humans occurred naturally, through chance interactions with animals.

Notably SARS-CoV classic, the most closely related human CoV, did exactly this.
Contrary to popular lab leak narratives, there is increasing evidence that supports zoonotic spillover. The more you look, the more this resembles the circumstances that led to SARS classic.

This evidence concerns the capture, farming, transport, and sale of live animals.
Early on, a large cluster of cases was associated with the Huanan Seafood Market, but not all. At first, it looked like this was a human super spreader event, as there were earlier cases not associated with the market.

Early reports also claimed there were no live animals there.
However, these earlier cases were associated with other markets. And it turns out the thing about the live animals?

I could insert a Maury Povich "that was a lie" GIF but I'd rather provide actual evidence: namely, this paper from June.
nature.com/articles/s4159…
This proves that not only were live animals sold at markets in Wuhan, but they included species with known susceptibility to SARS-CoV-2, including palm civets & raccoon dogs.

Both species were sold in markets in Guangdong in 2003 & were instrumental in SARS classic spillover.
"But Angie, how do you explain the fact that animal samples tested negative, both in early 2020 & in the 2021 WHO mission?"

Simple. If you look in the wrong place, you're not likely to find anything. They didn't test species that were representative of the animals being sold.
"But Angie, what about the fact that not all the early cases were at the Huanan market?"

We wondered this too, so we examined both the earliest available sequences and the circumstances of these cases. Early on, SARS-CoV-2 diverged into 2 lineages that circulated simultaneously.
Lineage B is associated with the cases at the Huanan market. Lineage A is not, but contains a case with links to another market (which is inconveniently covered up by the pre-proof watermark, so I added a slightly older version here).
"But Angie, I heard that other case went to a RT Mart, which is like a Costco with no live animals! I even saw a bunch of Costco GIFs about it."

The RT Mart case was actually a lineage B sequence. The lineage A case went to a wet market that DID sell live animals.
"But Angie, how do you explain the minor genetic differences between lineages A and B, if there were multiple markets involved?"

It's true A and B differ by only 2 nucleotides. It's also true that you'd expect more diversity if there were multiple spillover events.
In animals from different places with the same virus circulating in them, you'd expect to see very distinctive genetic markers of each lineage. The only exception would be if the animals were *originally* from the same place and were all one population.
And that's exactly the situation here. The live animals sold in Wuhan's markets were obtained through a common supply chain. Animals were transported together to Wuhan from locations where they were trapped or bred and then distributed to different markets.
It's not hard to see how a trader, courier, or vendor could have been infected along the way and seeded infections of viruses that were just beginning to diverge into unique lineages throughout different markets in Wuhan.
"But Angie, did you include the DELETED SEQUENCES that were sleuthed out of the cloud in this analysis?"

Yep.

Our results were the same.
"But Angie, you can't actually answer anything conclusively about origins using just genomic sequence data!"

Good point. That's why we also employed a cutting-edge technique known as looking at a map. Geographic location is, after all, the sole piece of evidence for lab origin.
This map shows the home addresses of these early cases. They cluster around a number of markets where live animals w/ known susceptibility to SARS-CoV-2 were sold. Importantly, they are NOT close to the WIV campus where Shi Zhengli's lab is located, even as case #'s increased.
"But Angie, the WIV location on this map is the BSL-4 lab. Shi Zhengli said bat CoV work occurred at BSL-2 and BSL-3."

Clearly you've never done anything remotely close to high containment work. Every BSL-4 lab I've ever been to also has BSL-2 and BSL-3 facilities on site.
We also confirmed that the Shi lab is located at the BSL-4 campus, with multiple sources who have actually been to both WIV campuses and have direct firsthand knowledge of where the bat CoV work is carried out. We confirmed all locations here using GIS data from OpenStreetMaps.
And if you look at excess death data, it also tracks. Excess deaths from pneumonia increase near the markets, not the WIV campus where bat CoVs were studied.
This doesn't exclude the possibility that WIV employees might live here, but which explanation is simplest?

That the hypothetically infected WIV employees live near the markets?

Or that the virus spread among people living near the markets where it first emerged?
Now I ran out of threadable tweets, plus I have a day job to get to. But now that I've covered the evidence FOR zoonosis via spillover from do another thread later addressing the next part of the piece: the evidence AGAINST lab origin.

In the meantime, read the piece!
Ugh, "from live animals in markets". I'm still under caffeinated.

Read the piece, though!
cell.com/cell/pdf/S0092…

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More from @angie_rasmussen

2 Sep
My excellent colleague @akelvinlab has this right: we will have more variants as long as SARS-CoV-2 continues to replicate.

Also worth pointing out that we don't know much yet about C.1.2, but we do know that it's not "mutating faster." That wouldn't even necessarily be bad.
C.1.2 is an emergent lineage of variants, meaning it's actually a cluster of several different variants. Here's the preprint describing it, by @CathrineSch07 and colleagues:
medrxiv.org/content/10.110…
Misinterpretation of panel C in the above figure led to 🚨MUTATES TWICE AS FAST 🚨 insanity a few days ago. That's wrong.

The amino acid substitution rate (new mutations that result in a change in a protein) is on par with other emerging variants.
Read 19 tweets
31 Aug
Just came back to Canada after being a groomsman in the wedding of one of my dearest friends. This trip was a joyous occasion but also a stark reminder of how badly the US has failed in its COVID responses, and continues to fail.
1. US requires an antigen test to reenter. In Canada, you can get a company to come to your home to administer a proctored test at your convenience for about $75 US. We were asked to show our test results multiple times at YXE & YVR. US CBP did not ask for our test results.
2. At the wedding, I learned to my chagrin that there were going to be some eligible attendees who refused vaccination. The wedding was fully outdoors, but I was still concerned. I thought maybe I could provide rapid tests for all guests as a gift to the couple.
Read 13 tweets
19 Aug
So here's the final chapter in my thread just answering the lab leak community's "just-asking-questions" questions.

These threads all concern our paper exploring the evidence, fresh out of peer review today in @CellCellPress. Give it a look!
cell.com/cell/pdf/S0092…
But first, catch up with thread 1 here, where I present the evidence for SARS-CoV-2 zoonotic origin:
And thread 2 here, where I present evidence against lab origin, which I'll continue here:
Read 29 tweets
19 Aug
Okay, as promised here's the second part of this thread. Earlier today, I covered the evidence that points toward zoonotic origins. Now let's go over the evidence that points AWAY from laboratory origins.

Here's the paper, out today in @CellCellPress!
cell.com/cell/pdf/S0092…
Here's a link to the first thread in case you missed it. Like that thread, what this lacks in GIF-underscored innuendo will be hopefully balanced by a critical appraisal of the actual evidence.
And let's just get this out of the way: YES, Shi Zhengli's lab at WIV had isolated 3 bat CoVs from field samples. Dr. Shi also stated on the record these experiments were done in BSL-2 containment.

Could an accident have happened? Sure. Accidents have happened before.
Read 24 tweets
17 Aug
@jwgale has written a fantastic piece on the live animal trade in Wuhan.

While the lab leak contingent has blithely dismissed this origin hypothesis, there’s increasingly some really compelling signals that this deserves closer consideration.
bloomberg.com/news/features/…
The common refrain from lab leak proponents is “why haven’t we found the intermediate species like we did with SARS?”

Unlike with SARS, by the time WHO investigators showed up, the animals were long gone. But it’s clear they were there. Including many SARS2-susceptible species. Image
If you are into cover-ups, then consider this: the wildlife trade is illegal but highly lucrative. I’d argue that failing to mitigate the known* risk posed by a multi-billion dollar industry is more scandalous than a lab accident.

*this is exactly how SARS emerged 20 yrs ago Image
Read 4 tweets
17 Aug
I’m very glad the vaccines have been deployed and so far it doesn’t appear that there’s been any onward transmission. We’ve come a long way with Ebola.

BUT maybe it’s time to think of immunizing more broadly than just the ring approach?
The idea behind the “ring strategy” is that you swiftly vaccinate a few degrees of contacts of a known case, forming an immunized “ring” that protects those contacts and prevents transmission outward from that vaccinated circle.
The rVSV-GP Ebola vaccine provides very potent sterilizing immunity in the short term, so this works very well with an important caveat: it depends on quickly identifying cases and performing contact tracing. It also requires those contacts’ willingness to be vaccinated.
Read 13 tweets

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