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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
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
May 31, 2025 • 35 tweets • 12 min read
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…