Kristian G. Andersen

Should we just go ahead and retract our paper?

Slack / Private Message Drop, p.4 · original PDF · in context

Which, I don't know, in combination with wet markets and the like might increase the risk of an outbreak from a bat coronaviruses.We need an actual razor in Occam's razor.

Slack / Private Message Drop, p.5 · original PDF · in context

I also had a pretty heated discussion with him on one of the WH committee calls where I mentioned that the RBD would probably lead to high affinity binding and the furin site being active.

Slack / Private Message Drop, p.6 · original PDF · in context

The furin site is clearly active in tissue culture.

Slack / Private Message Drop, p.23 · original PDF · in context

They're not furin sites, but there seems to be some affinity specifically for12bp insertions (in T/C) - and of course, the furin cleavage site is exactly 12bp.

Slack / Private Message Drop, p.23 · original PDF · in context

When it comes to the selection argument, what is still most telling to be is the RBD.

Slack / Private Message Drop, p.29 · original PDF · in context

SARS-CoV-2 is already'perfect' for binding, so it doesn't need to - BUT that 'perfect' RBD is found in a pangolin CoV, so clearly it already exists in nature - no further adaptation needed it seems.

Slack / Private Message Drop, p.29 · original PDF · in context

On to better papers, this is pretty interesting - especially cats: https://science.sciencemag.org/content/sci/368/6494/1016.full.pdf Cat-like intermediate host?

Slack / Private Message Drop, p.44 · original PDF · in context

That'd explain the lack of positive selection in the spike (which really is *highly* unusual IMO) and also the acquisition of the furin site - it clearly seems like some sort of heavy passaging must have been required to gain that site.

Slack / Private Message Drop, p.58 · original PDF · in context

Is it possible that the furin site is advantageous during high passage scenarios (transmission) but maybe not so much within host?

Slack / Private Message Drop, p.59 · original PDF · in context

In that scenario, maybe the furin cleavage site is maintained during exponentially increasing outbreaks (like we have observed up until about a month ago), but might be lost during more low-transmission periods?

Slack / Private Message Drop, p.59 · original PDF · in context

To see ifthere's a link to transmissions, if we look at viruses sequenced in low-transmission places (or during low-transmission times) vs viruses sequenced in high-transmission places (or times), is there an association with the former showing more evidence of furin site loss than the latter?

Slack / Private Message Drop, p.59 · original PDF · in context

While I knew about the furin site insertion experiments, I did know realize this (that the insertion in SARS2 is exactly where they inserted it experimentally in SARS):https://twitter.com/Ayjchan/status/1266805310313967617?s=20

Slack / Private Message Drop, p.68 · original PDF · in context

When I talked to Farzan way back in the day he mentioned that the one thing he'd be looking for was whether SARS2 would lose the furin site under different conditions - we now know this to be true (primarily in T/C, but there are examples in people too - intrahost).

Slack / Private Message Drop, p.69 · original PDF · in context

The part I'm really struggling with is that at the end of the day, we really don't have any hard evidence one way orthe other - and especially given some of the recent evidence, we also can't rule out that somebody actually put it inthere.

Slack / Private Message Drop, p.69 · original PDF · in context

I find it peculiar that all these pangolins are showing up sick with all sorts of SARS-like CoVs though - I mean, these guys have been traded_forever_ and only now do we realize they have CoVs?

Slack / Private Message Drop, p.74 · original PDF · in context

I think the data is shifting pretty strongly towards mask wearing being (potentially highly) beneficial.

Slack / Private Message Drop, p.75 · original PDF · in context

@Andrew Rambaut have you had a look at the Beijing genomes?

Slack / Private Message Drop, p.81 · original PDF · in context

I have a hard time believing it has been circulating undetected for quite a while inBeijing, so could it be a virus than went human > animal > human?

Slack / Private Message Drop, p.81 · original PDF · in context

Clearly not a separate introduction, but it's again linked to a wet market so I'm wondering if it can bounce back and forth (surely this is possible based on e.g.the Dutch mink farms).

Slack / Private Message Drop, p.81 · original PDF · in context

Is it really possibly Beijing has had an outbreak for quite some time?

Slack / Private Message Drop, p.82 · original PDF · in context

> But there was no coronavirus in Beijing so why would you need to wear masks?

Slack / Private Message Drop, p.83 · original PDF · in context

I think the main problem here is not really how that pangolin sequence ended up having that RBD, but rather whether there's anything sketchy here from a scientific standpoint.

Slack / Private Message Drop, p.86 · original PDF · in context

I assume lockdown measures would affect these differently.

Slack / Private Message Drop, p.92 · original PDF · in context

IMO, this virus is much too dangerous with too many uncertain long-term effects to deliberately infect people - especially given the HUGE number of cases we have in this country.

Slack / Private Message Drop, p.104 · original PDF · in context

I'm SUPER uncomfortable with 30,000 people now getting the Moderna vaccine - can you imagine how detrimental thisis going to be for (COVID and otherwise) vaccine research if this vaccine actually isn't safe?

Slack / Private Message Drop, p.109 · original PDF · in context

This one about vaccines though is a really serious misstep.

Slack / Private Message Drop, p.128 · original PDF · in context

Again, we should totally expect reinfections so none of them are surprising - I just get really fucking grumpy when people talk about what we can learn about COVID immunity and vaccines from n=1 studies (some of which might be false positives).

Slack / Private Message Drop, p.147 · original PDF · in context

Doing that type of work with a novel (bat) CoV would constitute a non-trivial risk for sure - she does not mention whether this isBSL-2 or BSL-3, but likely the former.

Slack / Private Message Drop, p.149 · original PDF · in context

Probably the most jarring COVID abstract I have read in a paper I just got for review for Nature Medicine: _"Here, from 273 COVID-19 patients, we identified six cases of reinfection based on clinical, phylogenic, virological, serological, and epidemiological data.

Slack / Private Message Drop, p.151 · original PDF · in context

Yup, common sneaky anti-virus mechanism - it appears SARS2 might be especially good at doing this.

Slack / Private Message Drop, p.153 · original PDF · in context

They can of course refuse to distribute the vaccine, but the crazy thing here is that Trump likely has no or very little interest in actually distributing the vaccine - he just wants itapproved and then leave it to others to figure out what to do.

Slack / Private Message Drop, p.155 · original PDF · in context

Makes me believe the 'pre-circulation' hypothesis of a furin site-lacking virus in humans a little more (or other animals - maybe cat-like?).

Slack / Private Message Drop, p.206 · original PDF · in context

While there are certainly SS events, it's still not clear to me if events like these are due to a person being particularlyprone to spreading, or whether it's just the event itself (in other words - could any standard patient lead to these events, or does it take something special?).

Slack / Private Message Drop, p.212 · original PDF · in context

I agree it's a little counter-intuitive, but probably the binding to hACE2 is generally speaking more optimized for binding to the RBD (soit's inherently a higher affinity binding - no matter the RBD).

Slack / Private Message Drop, p.212 · original PDF · in context

There is NO significance to this and it's not worth commenting on - ANYBODY who does this type of work knows that sequences get updated every now and again, especially when the sequences are (a) important and (b) had a few low-coverage regions that might have had assembly errors.

Slack / Private Message Drop, p.224 · original PDF · in context

Some of them have the _exact_ same furin site.

Slack / Private Message Drop, p.227 · original PDF · in context

The Huanan market is on Line 2 as well (so is WIV) and where one of these early sequences differ from Hu-1, it is indeed ancestral (as in, the same as RaTG13).I think it's entirely possible these may be some of the very earliest patients and suspected in early December - only later to be sequenced.

Slack / Private Message Drop, p.240 · original PDF · in context

Doesn't really point to lab origins -although the registration dates are a little puzzling and I'm not sure if this particular hospital should raise a flag (ithas a weird name, but don't they all - some hospital bound to be first seeing patients...).

Slack / Private Message Drop, p.240 · original PDF · in context

Yeah, I'm not quite sure what Y453F is about - might just be marginally beneficial.

Slack / Private Message Drop, p.260 · original PDF · in context

A lot of diversity in the size of the various farms- especially in Denmark (not sure about NL - but I think they have more 'mega' farms).

Slack / Private Message Drop, p.261 · original PDF · in context

Yeah, 1977 is definitely an escape - and likely linked to vaccine work.

Slack / Private Message Drop, p.264 · original PDF · in context

And yes, likely vaccine work, although I'd argue that that's just one type of 'escape'.

Slack / Private Message Drop, p.264 · original PDF · in context

All of this is very interesting though - isn't this data most consistent with an early divergence (or two emergences)that we didn't capture at the time and that have no connection to the seafood market?

Slack / Private Message Drop, p.299 · original PDF · in context

ALL the pangolins have that one - none of the bats

Slack / Private Message Drop, p.299 · original PDF · in context

To be honest though - I think it was the only way they could get the politicians to wakeup, so they used it as an excuse.

Slack / Private Message Drop, p.307 · original PDF · in context

However, it's entirely plausible that different mutations can lead to similar conformational changes, that might give the virus a 'spreader' phenotype if N501Y pops up on that genetic backbone.We have seen N501Y before (e.g., Australia), but I don't know that any of those are associated with increased spread?

Slack / Private Message Drop, p.328 · original PDF · in context

Do you know if Wendy is going to be able to test neutralization from vaccinees in addition to convalescent patients?

Slack / Private Message Drop, p.329 · original PDF · in context

Spoke to the Danes this morning and saw some additional data not yet public - essentially the same picture as theUK, so this looks to be real-real. @Andrew Rambaut - they mentioned that the UK had tested the virus against convalescent plasma and there was_no_ effect on neutralization?

Slack / Private Message Drop, p.352 · original PDF · in context

I assume an updated spike protein should likely do it, but as you say, who knows (if it's not, I'm going toshoot myself).

Slack / Private Message Drop, p.367 · original PDF · in context

Is it possible it's directly interacting with the spike protein to determine e.g., binding?

Slack / Private Message Drop, p.380 · original PDF · in context

Yup - seems plausible that immune escape might be the most likely explanation here - whether linked to natural immunity or vaccine induced.

Slack / Private Message Drop, p.383 · original PDF · in context

Why that would lead to increased transmission, I'm not quite sure I understand - except if e.g., high ACE2 binding is associated with both escape and transmission (not implausible).

Slack / Private Message Drop, p.383 · original PDF · in context

We have seen Nelly a couple of times in the US too and never associated with increased transmission (although all of that might just be down to chance).

Slack / Private Message Drop, p.384 · original PDF · in context

I had nothing to do with that press release... just saying.

Slack / Private Message Drop, p.414 · original PDF · in context

Are we going to make an updated vaccine for each?

Slack / Private Message Drop, p.415 · original PDF · in context

Since there are NO official photos of @Andrew Rambaut on the interwebs, can we please start a meme with the guy on the left being Andrew and maybe the guys on the right being Oli?

Slack / Private Message Drop, p.432 · original PDF · in context

I assume likely all three > I think it's the problem that spike is wild-type - not stabilized as in the mRNA vaccines - am I right about this?

Slack / Private Message Drop, p.496 · original PDF · in context

I'm additionally worried that South Africa might have additional data on this vaccine we don't know about - they justcanceled their whole vaccine program with this one and that's a HUGE step you don't take lightly unless there are additional concern (?).

Slack / Private Message Drop, p.496 · original PDF · in context

@Eddie Holmes - do you know if this particular email will be made public as part of your FOIA?

Slack / Private Message Drop, p.514 · original PDF · in context

But overall, yes, I agree with the hypothesis and think the distinction of different waves being due to differentmitigation efforts is a good one - but as you say, massively politically charged.The fourth wave will likely be driven almost entirely by vaccine escape.

Slack / Private Message Drop, p.530 · original PDF · in context

Ifthis holds up, we might have a winner for near-perfect vaccine antigen - spike + E484K, 2P, and dFCS.

Slack / Private Message Drop, p.566 · original PDF · in context

Much focus turned to the Huanan market, where super spreading might have occurred, so we end up having very biased sampling early on.

Slack / Private Message Drop, p.598 · original PDF · in context

I'm not sure even Marc understands the difference between GOF and basic research, but I'm sure he considers everything that went on at the WIV to beGOF (it's not - most GOF has been done in Baric's lab).

Slack / Private Message Drop, p.614 · original PDF · in context

shared file(s): Re: wondering if you have any further thoughts about the lab origin idea

Slack / Private Message Drop, p.616 · original PDF · in context

It might be worth pointing out that the video was from inside the Huanan market and shows several potential reservoir hosts...

Slack / Private Message Drop, p.647 · original PDF · in context

No fact checking whatsoever? _Matt Pottinger: There was a direct order from Beijing to destroy all viral samples -- and they didn't volunteer toshare the genetic sequences._ _Matt Pottinger: There is a body of research that's been taking place conducted by the Chinese military incollaboration with the Wuhan Institute of Virology, which has not been acknowledged by the Chinese government.

Slack / Private Message Drop, p.651 · original PDF · in context

When we started looking into this there was no intel and hence it was more than appropriate to consider a lab leak apossibility.

Slack / Private Message Drop, p.667 · original PDF · in context

I appreciate the enthusiasm, but they might want to talk to experts before doing this crap. [shared file(s): Screen Shot 2021-04-06 at 6.54.07 PM.png]

Slack / Private Message Drop, p.683 · original PDF · in context

Totalconvenience sampling too and they didn't go after these specifically - I think pangolins might just be packed full ofCoVs, which is bloody scary.https://www.frontiersin.org/articles/10.3389/fmicb.2021.657439/full

Slack / Private Message Drop, p.696 · original PDF · in context

I wonder if we're blind because we're focusing so much on bats in Yunnan - is it possible these guys are coming from pangolins?

Slack / Private Message Drop, p.696 · original PDF · in context

It's unclear to me if that's because of a difference in how strong immunity is between infection vs vaccine, or whether it's just a question of time.

Slack / Private Message Drop, p.708 · original PDF · in context

I love that the main diss on our paper is this: "How is it possible that Sars-CoV-2 can dock onto human cells so perfectly after such a short period of time?

Slack / Private Message Drop, p.713 · original PDF · in context

Well, wait until they see that pangolin data and I think we have an answer...

Slack / Private Message Drop, p.713 · original PDF · in context

I can't imagine what his life must be like...https://republicans-energycommerce.house.gov/wp-content/uploads/2021/04/EcoHealth-Alliance-Letter.pdf

Slack / Private Message Drop, p.714 · original PDF · in context

Phase I and II trials for vaccines against novel viruses we don't know anything about?

Slack / Private Message Drop, p.732 · original PDF · in context

Might accelerate vaccination efforts in hard-to-reach areas...

Slack / Private Message Drop, p.735 · original PDF · in context

Yeah, I don't know what that embargo comment was about...

Slack / Private Message Drop, p.751 · original PDF · in context

I amof course well aware that that is not the intent of your letter, however, it should be clear that it will very likely fan theflames of xenophobia and conspiracy theories - with allegations of a lab leak having no scientific grounding inavailable evidence or data.As somebody with significant experience working in outbreak response with international governments and public health authorities - whether that be in 'the field', on the bench, or in front of the computer - I think it is important thatwe strongly support further evidence-based studies into the origin of the COVID-19 pandemic.

Slack / Private Message Drop, p.785 · original PDF · in context

RpYN06 is closest in most genes.• No mention of SARS-CoV-2 in old theses from WIV, including from 2019.https://twitter.com/TheSeeker268/status/1392575191763472388?s=20

Slack / Private Message Drop, p.790 · original PDF · in context

And this very key point - which was Zhengli's point too...

Slack / Private Message Drop, p.815 · original PDF · in context

I'm wondering if we could plot number or markets (or similar) across a map and show an association.

Slack / Private Message Drop, p.818 · original PDF · in context

Would be_hugely_ instructive, but I have no idea if Wuhan is special, or not, when it comes to these types of markets.

Slack / Private Message Drop, p.818 · original PDF · in context

... was just reading Relman's (unRealman?) email again to see if we missed anything (we didn't...) - love his conclusion: "But same thing with data in support of a natural spillover, revealing shipments of risky wildlife samples across China, into Wuhan markets, and around the world, as well as the incredible seen and unseen diversity ofcoronaviruses in nature.

Slack / Private Message Drop, p.818 · original PDF · in context

Because vaccine 'failures' may very likely not be down to the individual (didn't respond to the vaccine, insufficientimmunity, etc.), but rather down to epidemiology.

Slack / Private Message Drop, p.823 · original PDF · in context

As a vaccinated person, spend a lot of time with an unvaccinatedinfected person and you'll likely get COVID - the risk is obviously much less, but I'm not convinced our 95%effectiveness will hold up in a world of many unvaccinated people, variants, COVID still circulating, and, most importantly, social interactions back to near-normal.

Slack / Private Message Drop, p.823 · original PDF · in context

Do we know anything about how many wet markets?

Slack / Private Message Drop, p.829 · original PDF · in context

What's important about the two markets / two lineages isn't the fact that there are two lineages - it's that you have two independent lineages associated with two different markets.

Slack / Private Message Drop, p.833 · original PDF · in context

A novel bat virus would likely be grown inBSL-2, whereas some of the others are likely BSL-3 or even -4

Slack / Private Message Drop, p.849 · original PDF · in context

Eddie, the lab leak theory isn't a conspiracy theory, you know?

Slack / Private Message Drop, p.854 · original PDF · in context

Just had a meeting with Fauci and his team this morning - they get it and deeply appreciate what we're doing, sowe'll keep dancing...

Slack / Private Message Drop, p.858 · original PDF · in context

How this gets past editorial, I just don't understand - they must be desperate for anything lab leak related.

Slack / Private Message Drop, p.873 · original PDF · in context

This article is :fire: https://massivesci.com/articles/sars-cov-coronavirus-covid19-lab-leak-hypothesis/

Slack / Private Message Drop, p.879 · original PDF · in context

What's key here - if there was _evidence_ to support the lab leak, taking that latter path would (unfortunately) have been necessary.

Slack / Private Message Drop, p.879 · original PDF · in context

I suspect Baltimore may definitely be interested in signing - especially if we go via Vince.

Slack / Private Message Drop, p.881 · original PDF · in context

@Kristian Andersen I'm not sure exactly what they did officially, but people freak out and that effectively is a lock down - plus, of course, localized 'herd' immunity (likely won't last more than 6-9 months).My concern around the vaccine in particular, is that while we have updated shots ready to go into production, but they're all based and B.1.351 and B.1.617.2 is a very different variant.

Slack / Private Message Drop, p.910 · original PDF · in context

Would immediately invalidate the lab leak -although, of course, there's a lab there too...

Slack / Private Message Drop, p.916 · original PDF · in context

Do we know about WIV working in pangolin CoVs in the lab?

Slack / Private Message Drop, p.917 · original PDF · in context

I have a really hard time believing WIV had them - but I can totally believe the wildlife rescue center might have.

Slack / Private Message Drop, p.918 · original PDF · in context

Zeynep seems convinced by the lab leak - I'm assuming her story will be absolutely awful.

Slack / Private Message Drop, p.925 · original PDF · in context

Why he can do what so many supposed 'science' journalists can't, I don't know... https://www.latimes.com/business/story/2021 -06-08/nobel-laureate-baltimore-smoking-gun-for-the-covid-lab-leak-theory

Slack / Private Message Drop, p.935 · original PDF · in context

I'm so confused about this pangolin stuff - did we always know they were full of CoVs?

Slack / Private Message Drop, p.940 · original PDF · in context

I'm sure this'll be interpreted as the proof of a lab leak - I kinda just adds to the multi-market hypothesis and some Chinese scientists asked for the data to be deleted because Chairman Xi had made it clear that he is in charge.I hate to think what will happen to the authors of the deleted data once this goes online - I can't say I think their lives are not at risk.

Slack / Private Message Drop, p.949 · original PDF · in context

There might _very_ well have been Lineage A circulating at the Huanan market, but we didn't capture it because ofbias - e.g., SSE of Lineage B at that market.

Slack / Private Message Drop, p.955 · original PDF · in context

The idea that _any_ of the recent data make Huanan a less likely place for a spill-over is hugely flawed IMO - totally wrong.

Slack / Private Message Drop, p.955 · original PDF · in context

And just as reference point - Huanan market is in Jianghan.

Slack / Private Message Drop, p.971 · original PDF · in context

(pangolins also don't have that ACE2 glycan...)

Slack / Private Message Drop, p.1007 · original PDF · in context

I doubt it - I think this bugger might have some tricks outside that spike protein we so fondly focus on...

Slack / Private Message Drop, p.1019 · original PDF · in context

I think we all agree: • Lab leak a potential concern • Actual data strongly pointing to no lab leak • Biosafety needs to be strengthened given how widespread SC1-like and SC2-like viruses are across SE Asia I don't think anybody with expertise would disagree on any of these points

Slack / Private Message Drop, p.1033 · original PDF · in context

I can see Rand Paul has read our paper too - even mentions Bob by name (starts ~4 mins in): https://twitter.com/bennyjohnson/status/1480943104496652297?s=20.

Slack / Private Message Drop, p.1043 · original PDF · in context

Yeah, I think this is coming from Jeremy - this is what they say in the document: "These emails were originally produced redacted via the Freedom of Information Act and subsequently to Committee Republicans.

Slack / Private Message Drop, p.1046 · original PDF · in context

Here's the full email - Tony never replied back (he was probably busy with some important stuff - like vaccines, maybe...) [shared file(s): Screen Shot 2022-01-11 at 9.04.20 PM.png]

Slack / Private Message Drop, p.1048 · original PDF · in context

I _do_ wonder when Fauci realized there was a NIAID sub-contract to the WIV - probably late Feb/Mar.

Slack / Private Message Drop, p.1074 · original PDF · in context

Well, I guess we know what's coming: https://republicans-oversight.house.gov/wp-content/uploads/2022/02/Letter-to-NIH-Follow-Up1.pdf

Slack / Private Message Drop, p.1082 · original PDF · in context

Congress can subpoena foreign nationalsand while they can't do anything directly if you refuse to appear, it could/will have consequences for future travel tothe US.They can't subpoena any of us at the moment (unless they get bipartisan support - we have already looked into that and that seems unlikely), but all of that changes in November.

Slack / Private Message Drop, p.1084 · original PDF · in context

Drosten didn't know about the research at the WIV?

Slack / Private Message Drop, p.1087 · original PDF · in context

Might be worth lifting some language from my previous answers on this (especially #3): https://www.nytimes.com/2021/06/14/science/covid-lab-leak-fauci-kristian-andersen.html

Slack / Private Message Drop, p.1092 · original PDF · in context