Ryan Hisner Profile picture
Dec 14, 2021 6 tweets 3 min read Read on X
1/6 Imagine that: Omicron is undergoing phenomenally fast exponential growth in the US, just like in the UK, Denmark, and South Africa. Crossing the Atlantic didn't impair its transmissibility. Who could've guessed?

Dec 6—3%
Dec 7—7%
Dec 8—13% Image
2/6 Take it from the master himself, Trevor B: "There is an inevitable very large wave of Omicron. It's going to happen." nytimes.com/live/2021/12/1… Image
3/6 There's such an air of fatalism around all this, as if we are utterly incapable of doing anything that could dampen or avert a devastating Omicron wave. Hospitals are already at max capacity in many states. An Omicron tsunami approaches, & we collectively shrug our shoulders.
4/6 Epidemiologist @sanghyuk_shin of UC Irvine: "We need to take this seriously, starting now. If we have learned anything on how this virus operates—it’s that any kind of mitigation, the earlier the better...." voiceofoc.org/2021/12/local-… Image
5/6 "...There is really no evidence that suggests that Omicron is going to be mild, there’s no evidence that it is less virulent." Image
6/6 At a company Christmas party at an Oslo restaurant, 80 out of 111 young (ages 30-50), 2-dose vaccinated Norwegians were infected with Omicron. Only 1 of the 80 was asymptomatic (none hospitalized). I've never heard of an asymptomatic rate so low. It doesn't suggest mildness. Image

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More from @LongDesertTrain

Oct 22
I beg to differ! If it is not a sequencing mistake—and it looks clean—one of these BA.3.2 has something completely novel in SARS-CoV-2 evolution: an FCS-adjacent deletion!

One of the two QT repeats appears to have been deleted. I've never seen anything like this before. Image
Work by @TheMenacheryLab looked at a similar, more extensive, deletion. They deleted both QT repeats plus the next AA (∆QTQTN). In Vero cells (monkey kidney cells), it produced extra-large plaques & outcompeted WT virus—similar to furin cleavage site (FCS)-deletion mutants. 2/12 Image
But in human lung cancer (Calu3) cells, the ∆QTQTN-mutant replication was dramatically reduced (2.5 orders of magnitude), and in infected hamsters disease was much milder. 3/12 Image
Read 12 tweets
Oct 13
There's a new BA.3.2.2 from South Africa today. For the most part, there's been little substantial change in BA.3.2 over the past few months—mostly synonymous mutations & very little happening in spike.

But this new one has 3 spike mutations & looks quite interesting. 1/7 Image
For those not following closely, here's a 🧵 I made about BA.3.2 (not yet designated at the time) that I made some months ago, when it first burst upon the scene. 2/7
The spike mutations are T124I, N478T, & T678I.

N478T is a reversion to the ancestral AA, meaning it's gone from T->K->N->T in this lineage.

There and back again.

S:478 has been by far the most active site recently. We've seen K, T, I , E, R, N, L, M, and Q there of late. 3/7 Image
Read 7 tweets
Sep 26
Attenuation of the SARS-2 furin-cleavage site (FCS) continues apace. It's beginning to look as if some form of FCS-weakening mutation might well become fixed in the near future. Collectively, they are at ~12% globally—a totally unprecedented level—& rising quickly. 1/4 Image
In South America, this may have already happened. Recent sequences are scarce, but they nearly all have some sort of FCS-weakening mutation, mostly S:S680P in XFG.3.4.1, but with several others (S680F, S680Y, R683Q, R683W) contributing as well. 2/4 Image
The enigmatic anti-correlation between S:∆S31 & FCS ablaters—clear since summer 2024—is strong as ever. Here are the recent CovSpectrum stats for T22N & ∆S31 among all seqs & seqs w/FCS weakeners.

How exactly a 1-AA deletion in a distant region affects the FCS is unknown. 3/4 Image
Read 4 tweets
Sep 4
There's been some speculation about why, despite persistent immune activation, germinal center activity, & overall elevated Ab levels, LC patients here had very low anti-spike Ab titers. I want to highlight one interesting speculative hypothesis & offer another possibility. 1/10
The ever-fertile mind of @Nucleocapsoid proffers the possibility that exosomes could be responsible for viral spread in some tissue reservoirs. I don't know much about this topic and so don't have much to say at the moment, but I'm trying to l learn. 2/
I'll offer one other possibility: the deep lung environment (or some other tissue reservoir) favors either an extreme RBD-up or extreme RBD-down conformation.

Background: The receptor-binding domain (RBD) of the spike trimer can be up or down. It has to be up to bind ACE2... 3/ Image
Read 10 tweets
Sep 2
A fascinating new preprint w/one very unexpected finding suggests, I believe, that a large proportion of Long Covid may be due to chronic infection in a particular bodily niche, which could be crucial for finding effective LC treatments. It requires some explaining. 🧵 1/33 Image
First, a brief summary of the relevant parts of the preprint. They examined 30 people (from NIH RECOVER cohort) for 6 months after they had Covid, taking detailed blood immunological markers at 3 time points. 20 had Long Covid (PASC), 10 did not (CONV). 2/ biorxiv.org/content/10.110…Image
The PASC group showed signs of persistent, pro-inflammatory immune activation over the 6-month time period that suggested ongoing mucosal immune responses, including elevated levels of mucosa-associated invariant T cells (MAIT). 3/ Image
Read 33 tweets
Jul 30
Wow, BA.3.2 hits its 4th continent with a new sequence from Western Australia.

Reminder: BA.3.2 is a saltation variant resulting from a ~3-year chronic infection. It is very different from and more immune-evasive than all other current variants. 1/4 Image
It was collected July 15, & is most closely related to the recent S African seqs from May & June.

It has an NSP5 mutation known to be beneficial (ORF1a:K3353R) & 2 new NSP12 mutations, which is unusual. Its 9 synonymous mutations indicate it has been circulating somewhere. 2/4 Image
Seems clear now that BA.3.2 is not going away anytime soon. Its overall impact so far has been negligible, but at first BA.2.86's was as well. Once it got S:L455S (becoming JN.1) the dam burst & it set off a new wave in the global North. The question now is.... 3/4 Image
Read 4 tweets

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