Continued surveillance and variant analysis is important, as highlighted by the emergence and spread of BA.3.2. Lack of data sharing by GISAID is bad news.

This is a total outrage and has crippled SARS-CoV-2 variant tracking and evolutionary analysis. Updating a file and giving access to Nextstrain & Cov-Spectrum does not require extensive resources, so the official justification is a lie. There has to be an ulterior motive here.

BA.3.2 has arrived in the UK. One BA.3.2.2, collected October 5, was uploaded from Scotland today. Same branch as recent BA.3.2.2 from Germany & Slovenia. It has a few errors (S:ins214:ASDT is misread & ORF1a:E4388K is an artifact). Ignoring those, the one notable new mutation is N:N126K.

One of the greatest. I recently saw a car with a bumper sticker that said "Remember the Edmund Fitzgerald." www.youtube.com/watch?v=FuzT...

BA.3.2 made it to New Zealand 👀

The cellular protease TMPRSS2 cleaves and activates the SARS-CoV-2 spike protein, priming it for membrane fusion and viral entry. This step is essential for efficient infection of airway epithelial cells.

First-world problem, I know, but I can't stand it when supplementary information is contained in 20 different files that have to be individually downloaded and viewed. Why not put it all in one PDF?

I can't reply to this comment, so I guess I'll quote-reply. The most recent molnupiravir sequences have indeed been from Australia, with the MOV stats for the most recent being pictured below. Once again, we see strong evidence that MOV-induced mutations are being positively selected. 1/4

BA.3.2.1 still hanging out in the Netherlands. Nothing new in spike in this latest one, though 3/4 nucleotide mutations are nonsynonymous (amino acid-changing) and all are in NSP3.

I beg to differ! If it's 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. BA.3.2 is a different beast.

Due to antigenic imprinting (also called "original antigenic sin", or OAS) the antibody response is slow to turn, but turn it will, with enough repeated, UPDATED vaccinations. Or repeated infections, I suppose, if you prefer suffering and poor health.

Reminiscent of Thorstein Veblen's work. Jobs with "no taint of usefulness" are the most respectable—and the most highly paid—while manual labor or anything smacking of usefulness "is of course on a precarious footing as regards respectability"—and, it goes without saying, are poorly paid.

Bad. No justification, no communication, no standard procedures for making changes—just arbitrary pronouncements cutting off access to some of the most valuable resources we have.

#BA32 remains detectable in a substantial fraction of Perth clinical samples for the week ending Oct 5, though total sequence and case numbers remain low.

Fool me once....

The final published version of this study is now available in Journal of Virology at journals.asm.org/doi/10.1128/...

I realized later today that I'd given the S:T124I mutation in this new sequence short shrift. T->I amino acid changes may be the most common type, yet it's very rare (<0.01% of sequences). Why? Because it removes a conserved glycan from N122! (Which is also conserved in SARS-CoV-1). 1/3

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. 1/6

Finally, CoV-Spectrum is meeting trees 🌳 – this week, we released a new feature to browse the SARS-CoV-2 UShER tree on CoV-Spectrum. With the new feature, you can see a subtree of your variant of interest. 1/4

I just updated our cryptic lineage dashboard if anyone is interested. Viewer warning: this site contains a ton of actual data that really long persistent COVID infections are still occurring. 1/ dholab.github.io/public_viz/0...

"The Great Pumpkin"—@siamosolocani.bsky.social's apt nickname for BA.3.2—has now shown up in New South Wales, Australia, for the first time. Together with its continued presence in clinical samples and wastewater in Western Australia, this confirms real community BA.3.2 transmission in AUS. 1/3

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

I'm guessing it will mostly stay there, but it's certainly very interesting that the two most interesting (in my opinion) currently circulating variants—BA.3.2 and PE.1.4—are both circulating mostly in Australia (at opposite ends of the country). 1/4

100%. See @deanbaker13.bsky.social for detailed proposals on how this could be easily done and would save hundreds of billions of dollars a year (about $400 billion in the US alone), not to mention the lives saved and improved. www.youtube.com/watch?v=cJJZ...

Being Anti-Fascist is important but we need to also be aware about Fascism's root causes.

Cryptic dashboard!

Another molnupiravir sequence from Australia showed up today w/extremely strong evidence of positive selection for MOV-induced mutations, a sign the genetic diversity created by MOV is being utilized to the virus's advantage. Similar signals have been in almost every MOV sequence in recent months.

For reasons unknown, the ∆S31 spike deletion in KP.3.1.1/XEC/LP.8.1.1 disfavored FCS-weakening muts that otherwise appear advantageous in BA.2.86. With ∆S31 mostly gone, the growth of FCS weakeners is proceeding apace & approaching 8% global prevalence. Pre-BA.2.86 peak was ~0.3% 1/2

In new study led by @ckikawa.bsky.social, we provide near real-time data on human neutralizing antibody landscape to influenza by measuring ~26,000 titers to >100 recent viral strains Data can inform vaccine selection & evolutionary/epidemiological modeling www.biorxiv.org/content/10.1...

I think there must be a disconnect between wastewater and actual rhinovirus infections. Biofire is registering another huge RV surge upon the start of the school year, as they do, without fail, every year. Inverse SARS-2/RV relationship still looking strong, BTW. @mackayim.bsky.social

The Dark Ages of health care in the rest of the developed world is the present-day reality in the USA. We docilely accept that if a person gets cancer, they'll likely lose their house or their life savings. Any threat to impose that system elsewhere would be met with fierce rebellion. We are sheep.

N*-enhancing silent double-nuc mutation on the move?

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

Thanks @ryanhisner.bsky.social for the super considered thread on the Kwissa et al preprint - making a case for a viral reservoir in the lung as a potential driver of long COVID. Some earlier thoughts from us on viral persistence in the piece below. theconversation.com/long-covid-a...

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

The three BA.3.2.2 from Western Australia appear to form an independent branch, but that's only due to the very low quality of the sequences. After making a few manual fixes, I got them to show up on the correct branch, next to several of the most recent South African sequences.

Sequences resulting from failed molnupiravir treatment still show up now & then & still almost invariably display strong signs of positive selection of MOV-induced mutations (suggesting MOV muts are increasing viral fitness). Mostly from from Japan & Australia now. Latest is an NB.1.8.1 from Aug 4 👇

Phenomenal work here. I'm curious about the very small number of exceptions to this—non-RBD mutations that increase Ab evasion & ACE2 binding. For RBD muts, this is readily explainable. Any ideas how non-RBD mutations might achieve this? Three in particular interest me: T22N, L629V, & A852K. 1/7

Wanted to flag this interesting study led by our collaborators @kinglabipd.bsky.social suggesting that at least in some contexts, the immunogenicity of H5 influenza vaccines can be improved by mutations that stabilize the HA protein.

See Fede's quick three-post thread for the latest fine details on circulating lineages, something he is THE leading global authority on. Also, a cool song recommendation at the end by a band I'd listened to years ago but had almost entirely forgotten about.

Reminder that FCS insertions are not rare or unusual & tend to resemble the OG SARS-2 FCS insert—7/9 nucs are G's in this one, consistent w/the normal G-heavy pattern of that dominates SARS-2 insertions. 1 seq uploaded today of this, which is actually in 7 sequences overall from late 2024. 1/3

Adding to the A->G cluster list: two chronic-infection LP.8.1.1 seqs from Ontario, Canada, from June have 10 A->G muts in a 101-nuc stretch. A few other sequences have had similar A->G clusters in this ORF3a region. Still unsure if this phenomenon is unique to SARS-2 or what the mechanism is.

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

Cool study looking at persistent infections among people in the UK's matchless population surveillance, in which a representative slice of the population was regularly tested. The infections were mostly not super long, but this is among people who are not generally immunocompromised. 1/3

‘We faced hunger before, but never like this’: skeletal children fill hospital wards as starvation grips Gaza

Expanding on the S:A852K/S:D843G/NTD-deletion connection described in the thread below, there's one other extremely rare BA.3.2 mutation with an uncanny connection to D843G—S:K795T, seen in just 53 sequences ever prior to BA.3.2. 1/4

Amid the incessant barrage of depressing science news, the development of Pathoplexus is a refreshing contrast—thanks to the work of @theo.io, @arambaut.bsky.social, @firefoxx66.bsky.social, & others. With funding, Pathoplexus could abolish the many insanities now plaguing genetic surveillance.

Latest BA.3.2 from Gauteng, the first collected there since Nov 2024. New spike mutation: S:Q677H The number of private spike muts in this BA.3.2 & the recent BQ.1.1.1 from Canada (which has also transmitted at least once) that are identical (yellow) or at the same site (aqua) is astonishing. 1/5

Quick question for the protein-structure gurus & spike mavens: Can you confirm that everyone has been wrong about the location of the SARS-CoV-2 spike fusion peptide all along? Is it pretty universally accepted now that it's S:868-909 instead of S:816-834? Seems that way www.cell.com/cell/abstrac...

Important insights into FCoV-23 cell entry from the @veeslerlab.bsky.social Freely available: www.nature.com/articles/s41...