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

Jun 19
Interesting recombinant showed up today from Texas. It's a mixture of B.1.595, BA.1, and some flavor of JN.1. Most of the genome is from B.1.595. The ancestry of this one is clear: it directly descends from a B.1.595 sequence collected in January 2023, also in Texas. 1/11 Image
When the B.1.595 was collected this infection was >1 yr old, w/no sign of Omicron. BA.1 ceased circulating ~1 year prior.
Now a BA.1 spike appears w/just 5 changes from baseline BA.1, none in the RBD—S12F, T76I, Q271K, R765H, S939F.

This is a zombie BA.1 spike. 2/ Image
There are only a few signs of JN.1, & they're scattered. In ORF1a, we see JN.1's V3593F, P3395H, & R3821K, but the NSP6 deletion btwn these—universal in Omicron—is absent. In
M has JN.1's D3H + T30A & E19Q (in JN.1 & BA.1), yet A63T—also in both BA.1 & JN.1 is absent. 3/11 Image
Read 11 tweets
May 31
An awesome preprint on the novel, unsung SARS-CoV-2 N* protein came out recently, authored by @corcoran_lab & Rory Mulloy. I’ve previously written on N*’s demise in XEC, the top variant in late 2024/early 2025. But…
1/34
…this preprint, along with another great study by the @DavidLVBauer, @theosanderson, @PeacockFlu & others prompted me to take a closer look...
2/34biorxiv.org/content/10.110…
...and for reasons I’ll describe below, I now believe rumors of N*’s death are exaggerated.

First, XEC is in terminal decline, replaced by variants with full N* expression, so N* is back in fashion.
3/34
journals.plos.org/plosbiology/ar…
Read 35 tweets
May 15
@DameSunshine @SharonBurnabyBC B.1.1.529 wasn't/isn't a real variant; it's a placeholder that represents a putative ancestor of BA.1/BA.2/BA.3.

Bad sequences and/or coinfections tend to get categorized as B.1.1.529:—they have enough Omicron muts to be ID'd as Omicron but so much dropout/mixed signals...
1/
@DameSunshine @SharonBurnabyBC ...that a specific designation isn't possible. Travel sequencing in the US is done by Ginkgo Bioworks. Their sequences are generally poor quality & they upload *pooled* sequences—against database guidelines. The B.1.1.529 here are likely low-quality/pooled sequences from GBW.
2/
@DameSunshine @SharonBurnabyBC I think it's entirely possible that a new, divergent variant will emerge this summer. There are hints with BA.3.2 & a 50-spike-mutation BQ.1.1 that has transmitted at least once. Other similar chronic infection-derived variants are undoubtedly lurking all over, unsequenced.... 3/
Read 4 tweets
May 2
Incredible how quickly @yunlong_cao & co provide us w/info on the latest emerging SARS-CoV-2 variants.

Already, we have great data on BA.3.2 (the divergent saltation lineage detected in South Africa & the Netherlands & NB.1.8.1, an emerging contender for global dominance. 1/9 Image
Image
BA.3.2 is a clear outlier on the antigenic cartography map—as expected given the enormous differences between its spike protein & every other circulating variant. 2/9
Image
It's unsurprising, therefore, that BA.3.2 evades antibodies from human sera more effectively than any other variant, though the degree of its superiority is striking. 3/9
biorxiv.org/content/10.110…Image
Read 9 tweets
Apr 25
About 1 month after this monster BQ.1.1 appeared, an even more extreme sequence has shown up in Alberta. Like the BQ, it has 50 private spike mutations, but it also has >40 AA mutations elsewhere in the genome. 1/6 Image
They include the full panoply of NSP3, NSP12, & N muts I've written about previously. ORF1a:S4398L is the most common mutation in the 4395-4398 region, this has ∆S4398, a rarity also seen in a few other extremely divergent seqs w/this constellation. 2/6 Image
In a theme that's become familiar, it's added two spike NTD glycans, N30 (via F32S) and N155 (via S155N+F157S).
Another chronic-infection leitmotif (first noted by @SolidEvidence): reversions to common or consensus residues in related Bat-CoVs, including SARS-1. 3/6 Image
Read 6 tweets
Apr 10
A fascinating SARS-CoV-2 sequence was recently uploaded—collected from a dog in Kazakhstan in July 2022.

Usher places the seq 1 nuc mut from the Wuhan ref seq—C21846T/S:T95I—i.e. pre-D614G. Could this seq somehow have a close connection to the first days of the pandemic?
1/19 Image
Of the sequences near this one on the tree, all are low-quality & clearly bad BA.1 or Delta sequences. The only genuine one is from the UK, collected April 2020. So it's likely even S:T95I was not inherited.

This sequence has several fascinating aspects. 2/ Image
(This all assumes the sequence is accurate and that C241T & C14408T (ORF1b:P314L) are genuinely absent. Its mutational characteristics make me certain this is a good sequence, though it's not impossible there's dropout not indicated hiding C241T and/or C14408T.) 3/
Read 19 tweets

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