Ryan Hisner Profile picture
Jan 28, 2022 10 tweets 4 min read Read on X
A thread of BA.2 updates.

BA.2 continues to do its thing in Denmark. The two most recent days of sequencing (January 20 & 21) recorded 74.2% BA.2 (285 of 384 cases). 1/9
The exponential increase in the proportion of BA.2 cases continues in the UK.

The apparent slowdown in growth in the past several days is entirely due to 0 of 8 sequences being BA.2 over the past four days & should therefore be ignored. 2/9
Similar exponential increase in the percentage of BA.2 cases in the US.

Again, the illusory plunge over the last five days is entirely due to a very small number of sequences and should be ignored. 3/9
My home state of Indiana had recorded zero BA.2 cases before last night's update, when six cases were recorded in the most recent week of sequencing, indicating a substantial percentage of BA.2. Major caveat: sample size very small. 4/9
Germany's BA.2 path is similar to what Denmark's was early on. A recent report found that 30% of cases in Berlin were BA.2, so as has been the case elsewhere, large cities with lots of international travelers are leading the way. 5/9
Japan finally has enough BA.2 to provide a decent indication of it's path. Surprise!—it's upward.

(Once again, the tiny sample sizes in recent days mean the illusory plunge at the end should be ignored.) 6/9
Not much sequencing in Portugal, but in the most recent day of sequencing, which was two weeks ago, all eight cases sequenced were BA.2. 7/9
Spain, like Portugal, has poor genetic surveillance, but is seeing a similarly steep rise in BA.2.

Small sample size makes this a pretty unreliable estimate, however. 8/9
Most of the other countries whose graphs I posted in a previous BA.2 update have seen little change. Not much has changed in Sweden, but I'll include it here since it has among the highest level of BA.2 among countries with decent sequencing. 9/9
I was rushed when putting together this thread and made a mistake in the number of BA.2 cases recorded in Indiana. There have actually been 12 BA.2 sequences in the most recent 8 days of sequencing, not 6. This gives Indiana the highest percentage of BA.2 of any US state.

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More from @LongDesertTrain

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
Jul 7
BA.3.2 update: another sequence from the Netherlands, June 18 collection.

It belongs on the same branch as the GBW travel seq (tree gets confused by ORF7-8 deletion). Also, there are 3 artifactual muts in the GBW sequence (as usual), so the branch is shorter than it looks. Image
Bottom line, in my view: BA.3.2 has spread internationally & is likely growing, but very slowly. If nothing changes, its advantage vs circulating lineages, which seem stuck in an evolutionary rut, will likely gradually grow as immunity to dominant variants solidifies... 2/9
So far, this seems like a slow-motion version of what we saw with BA.2.86, which spread internationally & grew very slowly for months. But then it got S:L455S & exploded, wiping out all competitors. Will something similar happen with BA.3.2? I think there's a good chance... 3/9 Image
Read 9 tweets

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