We need to talk about that human case of H5N1 in Texas...

Here is a bootstrapped (NJ) tree showing how the closest realtive of H5N1 sampled in cattle is a virus the infected an male individual who reportedly worked on a farm with cattle (dairy, I believe). I used all-8-genome-segment concatenated sequences for this analysis, with the help of @evogytis, for this, for maximum signal. Bootstrap values show strong support for the (human + cattle) grouping.

Important update on metadata of H5N1 in cattle (and back to birds):

Thanks to the extraordinary detective skills of @flodebarre, we are pleased to be able to share this table containing locations and dates for several H5N1 cases in cattle and birds:

github.com/andersen-lab/a… We have pseudomized specific location data relating to individual farms/herd/operations, and are only sharing location to state.

Into the weeds:

One reason it is particularly frustrating that full metadata has not been shared for genome sequences my colleagues and I have assembled from raw sequence read data released by @USDA / @USDA_APHIS, is that without those dates... it is not possible to test some really important hypotheses.

Years ago, staring long enough (weeks) at evolutionary trees of all 8 flu A genomes segments that stored on my kitchen table, it finally occurred to my brain that you can't just assume that these viruses evolve...

A few thoughts on the role of pigs in the emergence of influenza A virus in mammals.

1. It is simply not the case that movement of flu viruses into non-swine mammal species requires pigs as a "mixing vessel". 2. Here is a list of mammalian influenza A lineages that *did not* require the involvement of pigs:

Canine flu
Equine flu
Phocine flu
Now bovine flu.
I'll save you a google search: "phocine" = seals/sea lions.

So, *preliminary* molecular clock analyses indicate that the time of the most recent common ancestor (TMRCA) of the US cattle flu clade was late December.

TMRCA of that clade and the closest relatives in birds, mid-December.

If single intro, likely between those rough dates. Team effort:

@xrayfoo @flodebarre Kristian Andersen @LouiseHMoncla @swientist @meera_chand @MOUGK @EvolveDotZoo @stgoldst @stuartjdneil @PeacockFlu Andrew Rambaut @angie_rasmussen David Robertson @suchard_group @LemeyLab @jepekar @josh__levy Joel Wertheim @LrnM9

OK, I think we're close to decisive evidence that US bovine H5N1 had a single origin from birds, and that when related viruses from birds *have* been found, they are jumps from cattle back into birds.

Grackles, blackbirds, chickens all show mammalian adaptation like PB2 M631L. My understanding is that these bird (and cat) viruses within the "bovine" clade were sampled from farms that had bovine H5N1.

So, are the birds on these farms giving this virus to the cattle, or are the cattle giving it to the birds? It is cattle to birds very likely.

Here is a link to 239 consensus genome sequences, assembled by @xrayfoo, from sequencing reads of 2.3.4.4b H5N1 influenza A virus from cattle and other species.

github.com/andersen-lab/a… We very grateful to the scientists @USDA / @USDA_APHIS for their release of the important raw data from which these sequences were inferred:

ncbi.nlm.nih.gov/bioproject/PRJ…

I want to share a roadmap of how recently-shared data from the Chinese CDC, from environmental samples taken at the Huanan market, can be used *right now* to try to track down its animal sources.

The data have been around since very early 2020...

1/ and most were the basis of this preprint from >1 year ago by George Gao and colleagues. They are metagenomic sequencing reads from surfaces at the market like the wall of a vegetable stall, or the floor of a shrimp stall.

assets.researchsquare.com/files/rs-13703…

2/

1/16 I recently gave a public lecture about SARS-CoV-2 origins that touched on some of the myths & misinformation promoted by some proponents of a lab leak origin (below).

But I'd like to discuss a couple others here that I didn't have time to get into.

2/16 First, there is the talking point you've probably heard many times that there is something inexplicable about a new SARS-like coronavirus emerging in Wuhan because it is *so* far away from where the ultimate progenitor in bats existed.

Dear @KatherineEban, @jeffykao and @propublica:

Your recent story misquotes me in multiple ways, including ones that I contacted you about multiple times.

Astonishingly, you managed to ignore my corrections AND quote my concerns that you might do so!

propublica.org/article/senate… At 6 pm ET on Oct 26 2022 I wrote you:

"Our two recent papers establish that a natural zoonotic origin is a plausible scenario for the origin of the pandemic."

@jeffykao and @KatherineEban. Because you have not given me sufficient time to respond fully to your queries about @SenatorBurr's upcoming commission report on the origin of COVID-19, nor made it clear that you would incorporate the additional information... I said I would provide, I've decided to respond publicly and transparently so there is a record of what I have to say that won't be ignored or filtered through you.

Another unpublishable-by-a-scrupulous-journal "critique" of our recent papers in @ScienceMagazine is out.

Our conclusions *definitely* rest on "the likelyhood [sic] of susceptible animals being present in Wuhan, and only Wuhan of all locations in China". Great job, guys. We of course never argued that susceptible animals were only present in Wuhan. That is either ineffably ignorant or disingenuous. Whatever the case, they clearly have a desired conclusion they want to bend the evidence to fit.

Key misunderstanding here - probably helpful to explain not just to this person but to others who it may also help. It is a subtle point - but is covered in the article.

We didn't (& one shouldn't) expect cases linked to the market to live in locations centered on the market.

https://twitter.com/danwalker9999/status/1559024740227944448

Most of these people worked at the market and will have been infected at their workplace. So their residential proximity to the market is just a function of the tendency of people to live somewhat close to where they work. Not centered on it.

The point of the paper --

Great article from Eddie Holmes on many of the key scientific, political and social aspects of this question.

In science we can't prove things, so I wouldn't have chosen the title. But our studies *should* lay to rest "lab leak" origins (multiple).
1/n

theconversation.com/the-covid-lab-… The Huanan market was *the epicenter* of the pandemic. It does not represent "just a superspreading event". If you read our papers, rather than the errors and, yes, lies of the merchants of mis/disinformation who will soon fill up the comments section here, you will see...
2/n

Highly recommend this article from @amitkatwala of our recent papers on the origin of the COVID-19 pandemic.

Great to see quotes from an (amazing) early-career researcher, @jepekar, as well as Joel Wertheim and @K_G_Andersen.

wired.co.uk/profile/amit-k… And good to see this point, that my co-authors and I have been keen to talk about: our analyses that reveal the Huanan market as the epicenter of the pandemic could not have been done without Chinese researchers generating the data and Chinese authorities sharing them.

When your last, best move is to lie (or to capitalize on your prodigious ignorance and dimness).

Just as expected, Matt Ridley has used his platform at the @Spectator to spread mis/disinformation about our recent papers in @ScienceMagazine.

spectator.co.uk/article/has-th… In an article filled with out-of-context quotes and a mix of lies and/or inaccuracies (hard to tell the difference because Matt has a grasp of the facts strong like Mr. Burns), he laments that a BBC headline writer made his manor an unsafe space for a moment by being accurate:

Twice now I've seen people tweet the following sentence from the introduction of our recent paper out of context:

"However, the observation that the preponderance of early cases were linked to the Huanan market does not establish that the pandemic originated there." In each case the twitterer's laughable assertion: this is our admission that our paper (entitled "The Huanan Seafood Wholesale Market in Wuhan was the early epicenter of the COVID-19 pandemic") does not establish that it was the pandemic's epicenter!

science.org/doi/10.1126/sc…

Our preprints on the origin of SARS-CoV-2...

https://twitter.com/MichaelWorobey/status/1497607313397481472

have now been peer reviewed and published as a pair of Research Articles by @ScienceMagazine In the first paper, our analyses (1) show that the Huanan Wholesale Seafood market in Wuhan, China, was the epicenter of the COVID-19 pandemic and (2) indicate that the emergence of SARS-CoV-2 occurred via the live wildlife trade in China, which was active at the Huanan market.

🚨🚨🚨
Well here's one I missed since May 24 by Chang et al.

Thanks to SAGO report for the tip-off!

43,850 samples from 32,484 blood donors in Wuhan Sept to Dec 31, 2019.

*0* positive for SARS-CoV-2 by the definitive assay, neutralization titers. 1/

academic.oup.com/proteincell/ad… This squares perfectly with conclusions from our recent preprints that SARS-CoV-2 emerged LATE in 2019, likely November-December.

And that there were VERY few cases in Wuhan until later in December. /2

zenodo.org/record/6291628…

My views on recent VF article % famous "deleted sequences" study by @jbloom_lab:

Neat sleuth work. But mostly ‘stolen valor’ & unsupported accusations of malfeasance, laundered by a compromised peer review process. Allow me to explain. 1/103

vanityfair.com/news/2022/03/t… @jbloom_lab @jbloom_lab's study's main impact has been its non-scientific narrative, which, ultimately, erodes trust in science.

The Message: The Chinese engage in malfeasance to hide evidence of the origin of SC2. (Specifically which would disprove pandemic origin at Huanan market.) 2/

There was a key, overlooked, finding in our recent preprint.

Skeptical the pandemic started at the Huanan market? The strong evidence that lineage A, not just B, is geographically associated with the market needs your attention.

Long 🧵

https://twitter.com/MichaelWorobey/status/1497607313397481472

We found a very clear pattern whereby the earliest COVID cases, with onset dates in December 2019, were closely geographically associated with the Huanan market.

Here, the yellow circles are home locations of cases who worked at or visited the market, teal = no such link.