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Ryan Hisner Profile picture
@LongDesertTrain
May 2, 2025 • 9 tweets • 4 min read • Read on X
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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
Then why hasn't BA.3.2 grown and spread very much? Its ACE2 binding is quite weak, & most of this is due to its tendency to be in the "closed" RBD conformation, which helps evade antibodies but reduces ACE2 interaction & infectivity, a topic @jbloom_lab has explored. 4/9 Image
NB.1.8.1 and LP.8.1.1, which seem the two most likely contenders for future dominance, have quite similar spikes, though NB.1.8.1 exhibits slightly greater antibody evasion here. However, the sera was from patients in China, where NB.1.8.1 has had its greatest success. 5/9 Image
The population immunity environment is still, IMO, different in China (& to some extent in Japan, AUS, & NZ) than elsewhere, so whether this translates into rapid global growth is still an open question. However, NB.1.8.1 is starting to appear & grow a bit in USA & Canada. 6/9
See, for example, @SolidEvidence's excellent wastewater surveillance tool, Lungfish. While only at 1-2%, NB.1.8.1 mutations are growing. Some of this may be due to exports from China (which may be undergoing a Covid wave), though how much is uncertain. 7/ lungfish-science.github.io/wastewater-das…Image
Regardless of whether LP.8.1.1 or NB.1.8.1 wins out, the spike changes in both are modest compared to the variants of the past 8-10 months, so I don't think either is likely to have a significant effect on overall case levels.
8/9
BA.3.2, on the other hand, has characteristics of a variant that could drive a global wave, but its closed spike & weak ACE2 interaction mean that it would need to acquire additional adaptations in order to be widely successful. 9/end Image

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More from @LongDesertTrain

Ryan Hisner Profile picture
Dec 29, 2025
Very proud to be a co-author on this comprehensive preprint on the novel, growing saltation lineage BA.3.2, together with @Tuliodna, Darren Martin, Dikeledi Kekana, and lead author @graemedor. 1/9
I would normally write a summary 🧵 of the BA.3.2 mutational analysis here, but as much of my contribution parallels my previous BA.3.2 threads I'll just link to those here, w/brief descriptions of each.

This is my first, big-picture BA.3.2 🧵. 2/9
Short thread from June when the first travel BA.3.2 sequences showed up. I think my prediction from back then has pretty much been borne out. 3/9
Read 9 tweets
Ryan Hisner Profile picture
Dec 24, 2025
BA.3.2 emerged in Nov 2024 after ~3 years of intrahost evolution with >50 new spike AA muts, but since then, it's changed very little. Could the drug molnupiravir (MOV) galvanize BA.3.2 into pursuing new evolutionary paths? A new 89-mut MOV BA.3.2 seq suggests it could. 1/11 Image
Background on MOV: It's a mutagenic drug. Its purpose is to cause so many mutations that the virus becomes unviable & is cleared. But we've long known this often does not happen. Instead, the virus persists in highly mutated form & can be transmitted. 2/
I was an author on a paper published in @Nature that conclusively showed not only that MOV has created highly mutated, persistent viruses, but that these viruses have transmitted numerous times. See 🧵 below by lead author @theosanderson. 3/
Read 11 tweets
Ryan Hisner Profile picture
Dec 22, 2025
The most valuable viral research tools—@nextstrain & CovSpectrum—are being destroyed, not only blocked from new data but now forbidden from even sharing info from the PAST. Why?

Because GISAID is run dictatorially by a con man, paranoid egomaniac, & liar named Peter Bogner. 1/
I use CovSpectrum & Nextstrain every day—& I'm not the only one. Every Covid thread I've ever posted here has relied partly on CovSpectrum & Nextstrain for information & visuals. These vital tools have now been stolen from us by a world-class grifter. 2/ thinkglobalhealth.org/article/to-fin…Image
For years scientists knew something was very, very wrong with GISAID, but the breakout story (from which much of this 🧵is based) came 2 years ago in @ScienceMagazine from @sciencecohen & Martin Enserik. 3/
science.org/content/articl…
Read 22 tweets
Ryan Hisner Profile picture
Dec 9, 2025
3/77 sequences from the latest Netherlands upload are BA.3.2 as well as 4/86 seqs from Queensland, Australia, consistent w/the steady, slow growth we've seen in Germany, the UK, Ireland, & much of Australia.
1/4
One interesting (and possibly coincidental) aspect of the BA.3.2 tree: Two large branches have NSP14 mutations at adjacent AA residues—ORF1b:T1896I and ORF1b:H1897Y. 2/4 Image
I don't have any idea what functional effects either of these mutations would have. They are both C->T mutations, which is the most common type, but they've been relatively uncommon throughout the pandemic, with fewer than 8000 sequences combined. 3/4 Image
Read 4 tweets
Ryan Hisner Profile picture
Nov 22, 2025
Fascinating 🧵. The grotesquely mutated spike of this NJ Cryptic binds ACE2 very tightly.

It raises a broader question: Can cryptic wastewater-like lineages transmit?

YES

We knew it happened once. Now we know it's happened at least twice. The results were not pretty. 1/15
The first instance involved a small cluster of sequences that hospitalized several people & resulted in the death of a young child in early 2022. More on this one later. 2/15 Image
The most recent example requires some background. In late 2024, a spectacularly mutated Delta appeared in Spain with 40 new spike mutations and numerous Cryptic markers.

Normally, I would write a thread about such a remarkable sequence, but there were some issues... 3/15 Image
Read 15 tweets
Ryan Hisner Profile picture
Nov 5, 2025
Slovenia gets its first BA.3.2. Its (slow) geographic spread continues.

Also, 2/4 sequences uploaded from Western Australia (WA) today are BA.3.2.2.

If you're not familiar with BA.3.2, see posts 3 & 4 below for an introduction. 1/4
@StuartTurville has pointed out that WA delayed Covid spread longer than elsewhere in Australia. China has a somewhat similar immune history (as do other SE Asian countries). Perhaps BA.3.2 will do well in China once it arrives there? 2/4
Original BA.3.2 thread.
3/4
Read 4 tweets

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