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Ryan Hisner Profile picture
Ryan Hisner
@LongDesertTrain
Teacher "Be ruthless with systems and be kind to people." Michael Brooks, 1983-2020
Jun 4 • 14 tweets • 4 min read
New data from David Ho's lab showing that while adults & kids have ~equal antibody responses to XFG & NB.1.8.1, children have essentially no neutralizing antibodies to BA.3.2.

This seems to largely solve the BA.3.2 + kids mystery. 1/14 Image If you've missed the story about how BA.3.2 (a novel, divergent saltation variant) is hugely overrepresented in sequences from children, this was my original (very quick) analysis, which subsequent data extended & confirmed. 2/
Mar 26 • 18 tweets • 5 min read
So it's clear that BA.3.2 preferentially infects children, something we have never seen before in a SARS-CoV-2 variant.

Why?

The question's baffled me, but after a suggestion from Darren Martin, I think I have an explanation that makes sense.
1/16 I've tried to make sense of BA.3.2's penchant for kids by considering its unique spike: more compact, more closed, & more antibody-evasive than any other variant.

But I think another feature of BA.3.2 is responsible: its wholesale deletion of ORF7a, ORF7b, & ORF8 (∆ORF78).
2/
Mar 24 • 16 tweets • 4 min read
You have to wonder for how long we will continue seeing infections from 2020 continue to show up (in absurdly high quantities) in wastewater.
1/16 I suspect that the number of people continuously infected since 2020 or 2021 is much larger than we realize. It's impossible to prove, but there are case studies where a chronically infected person gets infected by a new variant, which drives out the original virus...
2/16
Mar 22 • 34 tweets • 9 min read
While the final outcome for BA.3.2 is uncertain, its unique characteristics—extensively remodeled spike NTD & SD1/SD2, novel S2 muts, & total deletion of ORF7a/7b/8—make it the best candidate for co-dominance we've seen, which could mark a new era in SARS-2 evolution. 1/ Until now, the broad pattern of SARS-2 evolution has been:

1) Emergence of a saltation variant originating in a chronic infection

2) Rapid growth/global dominance & a variant-driven wave of infection—especially if it emerges in late fall/winter (BA.1, XBB.1.5, JN.1). 2/
Dec 29, 2025 • 9 tweets • 3 min read
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
Dec 24, 2025 • 11 tweets • 4 min read
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/
Dec 22, 2025 • 22 tweets • 7 min read
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
Dec 9, 2025 • 4 tweets • 2 min read
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
Nov 22, 2025 • 15 tweets • 5 min read
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
Nov 5, 2025 • 4 tweets • 2 min read
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
Oct 22, 2025 • 12 tweets • 5 min read
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
Oct 13, 2025 • 7 tweets • 3 min read
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
Sep 26, 2025 • 4 tweets • 2 min read
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
Sep 4, 2025 • 10 tweets • 4 min read
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/
Sep 2, 2025 • 33 tweets • 10 min read
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
Jul 30, 2025 • 4 tweets • 2 min read
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
Jul 7, 2025 • 9 tweets • 4 min read
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
Jul 2, 2025 • 5 tweets • 2 min read
Quick BA.3.2 update. Another BA.3.2.2 (S:K356T+S:A575S branch) from South Africa via pneumonia surveillance.

This means that 40% of SARS-CoV-2 sequences from SA collected since April 1 (2/5) and 50% collected after May 1 (1/2) are BA.3.2. Its foothold seems strong there. 1/3 2 interesting aspects of the new BA.3.2:
1. ORF1b:R1315C (NSP13_R392C)—This mut is in all Omicron *except* BA.3. So this may well be adaptive.

2. S:Q183H—First known antigenic spike mut seen in BA.3.2, not a major one, but one we've seen before—eg, LB.1/JN.1.9.2.1 2/3 Image
Jun 29, 2025 • 11 tweets • 4 min read
BA.3.2 update, Chapter: "I'm Not Quite Dead, Sir"

A new sequence from a traveler to the USA from the Netherlands was uploaded yesterday, with a collection date of June 17. 1/10 Image This was a BA.3.2.1, the branch with S:H681R + S:P1162R (not S:K356T + S:A575S).

An updated, annotated version of the BA.3.2 Usher tree pictured below.

This sequence has the first new spike mutation since BA.3.2 emerged in November 2024—S:V227L. 2/10 Image
Jun 27, 2025 • 7 tweets • 2 min read
@yaem98684142 @TBM4_JP This analysis is extremely flawed.

There is nothing abnormal about BA.2.86 appearing in multiple countries shortly after discovery. This has been the norm lately w/reduced surveillance. 1/ @yaem98684142 @TBM4_JP The mutational spectrum analysis is poorly done. It cites a single study looking at the mutational spectrum in *three* immunocompromised individuals. Needless to say, this sample size is WAY too small. 3/
Jun 19, 2025 • 11 tweets • 4 min read
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