Private channel session 803
39 messages over 3h 50m, 2021-01-14 – 2021-01-14.
A “conversation” here is an activity session — a run of messages with under 60 minutes of silence inside it. The channel had no native conversation boundaries.
-
Jeez: ```We report the presence of a viral isolate from late December 2020 in Columbus Ohio that has acquired the S N501Y variant. This amino acid change was first described in a clinical sample in the United Kingdom in association with other novel S variants and a clade 20B backbone (ECDC, 2020; Davies et al, 2020), with the combination named as the B.1.1.7 strain and a Next Strain designation as 20I/501Y.V1 (Bedford et al, 2021). The same N501Ymutation was subsequently found in a clade 20C strain in South Africa, where it was associated with a different setof additional S variants (Tegally et al, 2020), with Next Strain designation as 20H/501Y.V3. ```What a fucking mess Trevor has created. "It has acquired the N501Y variant".
-
On that note, I am sure I read this hypothesis somewhere before: https://twitter.com/trvrb/status/1349774308202094594
-
Aye on both counts. Fucking Trevor!
-
That Ohio paper is well out of order. They say - UKnB.1.1.7 (clade 20I/501Y.V1) strain. This is not on - you can'tlabel stuff geographically.
-
`containing several likely pathogenic but distinct mutations in the Spike (S) gene, particularly N501Y.` - what? 'likelypathogenic'? Garbage
-
I think you can give this one a kicking on Twitter. Unfortunately, given the discussion about it yesterday I think I hadto post it. The reviewers can resolve all that stuff.
-
@Kristian Andersen https://twitter.com/Cornedbeefpyatt/status/1349776702239633409?s=20
-
Human geneticists love to use the term "pathogenic mutation". I wonder if that's where it's coming from... Real garbage. I'm glad Trevor supports our hypothesis... :wink:
-
I even discussed it with Eric Topol on his podcast!
-
REALLY????
-
:zany_face:
-
Yes!!
-
WOW
-
I still consider it MY (highly speculative!) hypothesis! MINE. MY HYPOTHESIS.
-
It's also in that ABC Australian podcast I did the other the day. But you can have it - I'm not 100% convinced yet. I'm not sure why evolution in individual chronic hosts will lead to convergent evolution for increased transmissibility atthe population scale. A few years ago we did a norovirus modelling study that said this sort of thing was unlikely, but that could easily be bollocks. https://academic.oup.com/ve/article/3/2/vex018/4055728
-
There is no evidence that there is increased transmissibility in either the Brazilian or South African strain.
-
It is clearly fit in the populations it is spreading in.
-
The convergence is possibly for cellular infectivity and immune evasion - all things that will be selected for in achronic infection without sterilising immunity. Strong competition between viruses for cells. However, my assumption has always been that this can only be likely to degrade transmissibility (given it was already transmissible at the beginning). But perhaps there is just a fortunate (for the virus) alignment of a within-host fitness peak and a between host one. And the latter involves too many intermediate steps with negative epistatic effects to reach in a stepwisefashion.
-
Within host (and with the additional benefit of recombination) these combinations are readily obtainable.
-
Given the low frequency of chronic infections compared to the huge number with 'normal' durations of infection, doesn't the fact that we are seeing the same sort of constellation of mutations evolve and spread 3 times independently suggest that they have a major advantage at the population level?
-
Yes - they do. But I think they can't get there by progressive steps in sequential infections - there are troughs (wesee all of these mutations appear individually many times).
-
So the chronic infections offer an opportunity for these to arise in combination. Chronic infections are rare as aproportion of infections but there are shed loads of infections now.
-
Indeed. Not saying the theory is wrong, just that there are some loose ends. I can only imagine how Alina and ganghave reacted to this: [shared file(s): s41591-020-01205-5.pdf]
-
Nice piece. Angie is a true hero. I can't imagine what she must put up with (you probably can more than me, Eddie, but women get it so much worse).
-
She's a 1000X times tougher than me. I find it very difficult and have to get off social media as much as I can. I also hate dealing with the mainstream media. She must get endless shit. No idea how she manages it.
-
Angie is indeed tough as nails - true hero! I *do* wonder if she has a hard time dealing with all the shit she must begetting - she _is_ moving to Canada after all. Can't blame for for leaving this dumpster fire - I'd do the same in aheartbeat if anybody up north wanted me.
-
There's an opening at the Wuhan Institute of Virology. Labs were recently renovated and cleaned.
-
> Yes - they do. But I think they can't get there by progressive steps in sequential infections - there are troughs(we see all of these mutations appear individually many times). Agreed. The way I'm thinking about this is that there must be an initial selection pressure that drives the fixation ofthose mutations - almost certainly, that selection pressure is intrahost. Once that variant is out - and it's more transmissible / able to evade immunity - then it's a different selection pressure driving its fixation in the population. Itoo just think there's a really unfortunate relationship between really fit intrahost, means you're really fit in the larger population. Separately, two vaccine failures en route to our lab - I sure as shit hope these are not B117! (they'reepidemiologically connected...).
-
How long after vaccination?
-
I believe this was just after receiving second shots - but importantly, in the presence of strong IgG anti-S titers.
-
Don't know if these titers are neuts though - something we need to test. We have a bunch inbound from Jordan too, but those are failures from one of the Chinese vaccines.
-
All vaccine failures in the UK will automatically go for sequencing - I am hopeful we will be told which ones they are but who knows.
-
Yeah, going to be really important over the next couple of months to understand what's going on here. The immunologists seem very (VERY!) sure there is no problem with the UK/RSA/Brazil lineages when it comes to immunity. I'm less certain.
-
I agree. If these constellations have no effect on vaccine elicited immunity then boy will we have dodged a bullet.
-
I'm almost certain they'll have _some_ effect on efficacy, but just not sure how much. Let's hope very little (say, 95%> 92%...)
-
Lord knows what the effectiveness is going to be anyway. We'll see...
-
Tangential to this, but important to fully understand just how tolerant SARS-CoV-2 is to mutations in immunologicallykey sites - HCoV-NL63 uses ACE2 as a receptor too and is very diverged from SC2. @Robert Garry - I don't know ifyou have looked more closely at that virus going through your alignments / structures?
-
YeaH do think there will be failures for the vaccines that don't use a stabilized spike. Erica Saphire and others have been preaching this, some folks don't listen. Same with Lassa vaccine, but that's an entirely different story. BTW - Iwas on call yesterday with Erica/NIH so I missed several Zooms.
-
Why they did not stabilize that spike I don't know - so simple, people! If we follow this crackpot theory a little bit, knowing that animals that received the OxAZN vaccine were not protected against infection (at all - vaccinated animals had as much virus as unvaccinated animals in the upper airways after challenge). Could the non-stabilized spike lead to a very narrow immune response with very few epitopes exposed, some of which might be suboptimal?If yes, then presumably the virus might be able to escape immunity quite easily by changing a limited set of amino acids - and, presumably, the same/similar set of AAs.We wouldn't see the same happen in natural infections - more complex to escape. We also wouldn't see the same from other vaccines - because, again, more complex.I don't know if this holds up... Seems like a reach to me - albeit, maybe not impossible?