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...

Intriguing new preprint of possible relevance to the bizarre A->G mutational clusters. I'm fascinated by long-range RNA-RNA interactions, and a long range one posited here binds ADAR1. Experimentally disrupting it decreases replication and A->G mutations. 🤔 1/6

If I found one of those genie-conjuring lamps, I think one of my wishes would be to know exactly which virus has infected me every time I get sick. The day is getting closer.

Much anticipated paper & superb 🧵 on SARS-CoV-2 evolution & the first full explanation of one of the defining changes in Omicron compared to pre-Omicron! Essential, seminal work here. Congrats and a big thank you to @turville.bsky.social, @snpoehlm.bsky.social, & coauthors of this invaluable work!

LOL. This is my favorite news genre now.

Wonkish speculation on the ultra-rare, 2-nuc S:A852K mutation in BA.3.2. In the BA.2 spike structure (PDV 7XIX), A852 is very close to both D568 and D574 (all three magenta below). Alpha likely created a new salt bridge (ionic bond) w/its A570D mutation (A570D-K854).... 1/16

BA.3.2 update: another sequence from the Netherlands, June 18 collection. It belongs on the same branch as the GBW travel sequence below it (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. 1/9

Australian COVID-19 deaths declined in 2023 and again in 2024, but SARS-CoV-2 is an additive source of death and a poorly quantified burden of chronic disease.

Quick update on BA.3.2. Another BA.3.2.2 (the S:K356T, S:A575S branch) from arrived 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

1/5 The recent detection of BA.3.2 suggests it's still circulating at low levels. Though rare for now, this variant could have important implications for SARS-CoV-2 evolution. Also see recent insights from @ryanhisner.bsky.social #COVID19 #Variants

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

Kidney stones are hell.

Addendum: maybe the most extensive A->G nuc cluster I've found that has multiple samples in different regions by at least 2 different labs (both very good ones, Yale & the CDC). 16 A->G nuc mutations across a 300-nuc stretch (ORF6-ORF7b) in a three-state US BA.1 branch. 1/3

AOC: No mercy. 🔥

(virological wonkery alert) Turns out there are quite a few of these A->G clusters, some even making up substantial branches in the past—an AY.74 branch had 11 A->G muts in a 380-nt stretch. 👇 These don't seem to occur for any other mut type—only A->G. 1/3 threadreaderapp.com/thread/18347...

🎯 Trump has always pretended to be anti-war, but his foreign policy has been mostly a cowardly imitation of Biden's atrocious policies—on Gaza, Yemen, Latin America, Iran, etc—and now he's committing acts of war, in illegal fashion, against Iran at the behest of Israel. This must stop.

New cryptic lineage popped up in the database this week. This time it is from Hillsborough, New Hampshire. The lineage is BA.1-derived, so from a 3+ year infection. This one is a classic. 1/

I've previously noted that recent molnupiravir sequences (meaning sequences whose mutations clearly originate in MOV treatment) have shown a marked trend toward positive selection of MOV mutations, i.e. MOV muts are increasing viral fitness. 1/7 bsky.app/profile/ryan...

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. 1/10

Great work by Josette documenting the NB.1.8.1 vs XFG. Huge differences by country, likely reflecting different immune histories, namely, a longer history of infection in Europe, North America, & South-Central Asia (favoring XFG) than in East Asia, New Zealand, & Australia (favoring NB.1.8.1).

Update: pneumonia surveillance in South Africa has delivered another BA.3.2; same branch as the German one—collected Apr 4 (the most recent SA seq). BA.3.2 in South Africa: March—0/9 April—1/2 This is the 1st BA.3.2 from Western Cape. Previous BA.3.2 were from Gauteng & KwaZulu-Natal. 1/6

One more BA.3.2 has appeared, this one in Germany (April 29 collection date). Like the one from Belgium, it has the spike insertion, ins214:ASDT, despite being from a different branch of the BA.3.2 tree (the S:K356T, A575S branch). I think this means the insertion was there from the beginning. 1/2

This is nuts. When will the madness end? Very glad @pathoplexus.org is up and running.

An awesome preprint on the novel, unsung SARS-CoV-2 N* protein came out recently, authored by @corcoranlab.bsky.social and @rorymulloy.bsky.social. I’ve previously written on N*’s demise in XEC, the top variant for several months, but… threadreaderapp.com/thread/18373... 1/34

Australia, Taiwan, and Japan seem to be the major molnupiravir users these days. Sometimes it's hard to tell if a new MOV sequence is from recent MOV use or treatment from the past—like this recent FL.20.1 whose closest relatives on the tree were collected ~1 year ago. 1/4