Private channel session 673
41 messages over 1h 55m, 2020-12-14 – 2020-12-14.
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.
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Another important article from Ed Yong
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"Academia's perverse incentives pushed overconfident poseurs towards sloppy work, which then got international attention. Many people swerved out of their scholarly lanes and plowed into unfamiliar territory, making life harder for actual experts. 6/" Yes Alina, Relman etc he is talking about you...
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I had a good half hour rant about this when I talked to him :wink:. Haven't had time to read the article yet - but I'm sure it's great...
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And don't be mistaken Alina is indeed talking about us here, but mostly you Kristian :sunglasses: [shared file(s): image.png]
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She _does_ talk a lot about me... :thinking_face:. I totally agree with her on this tweet though - a lot of high profile folks doing a lot of shit 'science'.
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Don't get me started - just out of the COVID review study section - let's just say that I regret not putting in acompetitive application...
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Hah. Next time
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@Andrew Rambaut - what's this UK SARS2 mutation stuff everybody is talking about today?
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Oh my fuck
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Oh boy.
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Here is a summary I have been sending round - is that this variant has spike N501Y (similar to an outbreak in South Africa but apparently independent and unrelated) but it also has 13 other non-synonymous mutations and 3deletions. There is some evidence that it is spreading quickly in SE England but it is not clear if this just means thatR is high in this region and this is just the variant that is involved. There is no evidence that the course of infection isdifferent but data is limited. Lab work is being started urgently.There is phylogenetic evidence that 3 cases in Denmark and one in New South Wales may have been the result ofimport from the UK cluster.
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Some estimates that Erik Volz and I did independently suggests that this may be spreading at a higher rate than other variants but we can't rule out just the luck virus getting into high R areas.
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However - and this is what really interests me is the 14 mutations and 3 deletions in one short (in time) branch. Ithink this must be the result of transmission from a chronic infection.
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Thanks Andrew for the background - that's very interesting (and I'll keep this to this channel for now). It's great tohear that the UK now have systems in place to even detect "mutations of potential interest" - what it means isobviously a much longer affair.I get annoyed with all the communication that's completely dug in - "it's no issue at all" and "OMG it's mutating". Canwe just agree that the truth is somewhere in-between and that it always takes time to figure out?
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As for chronic infection - I can totally believe that. Here's a case we recently picked up - seven month of SARS2 infection with negative PCRs in-between. Sky high titers when picked up in late October (6 months after infection -he remained positive into December). [shared file(s): fake-reinfection.pdf]
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I am normally fairly relaxed about RBD mutations - sure they happen and they may have antigenic effects but we can be pretty sure that they are not being antigenically selected for because there isn't enough standing immunity (inmost places) or vaccination yet. BUT... this chronic infection scenario worries me because it may well have selected for escape from the immune response raised by the wild type virus (and thus the vaccine). And now it is circulating widely.
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This is the set of mutations that are unique to this cluster: [shared file(s): image.png]
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Yes, agreed. Although reinfections also a concern here - I'm worried about selection in e.g., healthcare settings.Mink transmission also a concern here.My default is always "probably not an issue", but SARS2 really does appear to be pretty 'adaptable' and there's ALOT of transmission going on.
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Here is the tree... [shared file(s): Kent_N501Y_836.ml_annotated_collapsed_tree.pdf]
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That's A LOT of mutations - all in one 'jump'?
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There is one intermediate with some of the mutations... hence thought of a chronic shedder
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Yeah, the spike mutations would suggest chronic - but a lot of mutations outside spike too, which is a little peculiar tome.
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Chronic shedding with immune selection definitely a possibility. N501 is next to a short disordered region in S structures - a clear signal that it's an epitope.
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P681H is also VERY interesting....how common is this?
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There is an ORF8 stop at amino acid 27 and then a number appear after that suggesting it has become non functional.
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@Robert Garry Why do you say that?
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Any thought if it would likely be an immunecompromised patient - could a weak immune response enhance selection for escape? Or do we know of any asymptomatic shedders - which would allow for the transmission if the person was out and about?
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@Robert Garry It's the insertion P in PRRA
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@Robert Garry Would be surprising if it didn't affect cleavage...
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It's a little weird in that respect - the patient above essentially has no - or very limited - humoral immunity, but thesignatures still look like immune escape - or maybe something else is going on. So yes, even immunecompromisedpatients can shed viruses that may have signatures of immune escape.
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@Robert Garry Ooh. Missed that.
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@Robert Garry That's the one I'd be concerned about.
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@Robert Garry Oh, interesting. It's rare - but parallel evolution? [shared file(s): Screen Shot 2020-12-14 at 10.16.54.png]
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@Robert Garry P > H still have FCS, but affects glycans and likely regulation?
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Can you send a link to that nextstrain view?
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@Robert Garry Yeah both of those...
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https://nextstrain.org/ncov/global?c=gt-S_681
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"Or do we know of any asymptomatic shedders - which would allow for the transmission if the person was out and about?" This is the question we're going to answer one way or the other if the vaccines are not that good at sterilizing immunity (hopefully most are).
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My money is on sterilizing immunity - without that, oh boy...
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Oh boy is right - this is why I really really wanted to do human challenge studies.
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Yeah...