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
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/
There are only a few signs of JN.1, & they're scattered. In ORF1a, we see JN.1's V3593F, P3395H, & R3821K, but the NSP6 deletion btwn these—universal in Omicron—is absent. In
M has JN.1's D3H + T30A & E19Q (in JN.1 & BA.1), yet A63T—also in both BA.1 & JN.1 is absent. 3/11
Oddly, it has the 3-nuc, loss-of-function ORF6:D61L—from JN.1 since BA.1 lacks it.
It also took N:P13L & ∆31-33 from BA.1/JN.1 but lacks N:R203K/G204R (& therefor N*).
Finally, it has the standard ∆27934-29759 s2m deletion, which all BA.2 descendants have. 4/11
Also odd: None of the usual convergent chronic-infection muts are here. The Jan 2023 B.1.595 spike got 1 non-RBD spike mut—P1162S—in ~15 months & in ~2.5 years, the BA.1 spike has added just 4-5 subs, none in the RBD.
There's no sign of combat with an immune system. 5/11
It's nearly certain all these sequences are from the same person. When the B.1.595 sequence was collected in 2023, they were also infected with BA.1, but no sign of it showed up in the sequence.
Where was it hiding out? In the deep lung? In the GI tract? 6/11
But viruses that have spent long periods of time in the GI tract have distinct mutational signatures, as @SolidEvidence has documented. I've also discovered a distinct mutational pattern from bronchoalveolar lavage sequences (deep lung).
This sequence has none of them. 7/11
There's no chance this virus spreads in the current environment. But cases like this might have relevance in the long term. As immunity to successive Omicron variants grows, old variants may become newly fit.
But they long ago vanished.... or have they? 8/11
Apparently not. Usually, when old variants reappear after years, their spikes have transformed.
But this a 4.5-year-long infection that's never had a single RBD mutation.
In 5-10 yrs, something close to ancestral spike could be newly fit, esp. in children. 9/11
Could an ancient spike reappear at that time & take over? Something like this happens with norovirus. Norovirus variants that circulated years/decades ago sometimes reappear, relatively unchanged, & proceed to sweep the world. See paper by Chris Ruis. 10/ academic.oup.com/ve/article/6/2…
We've not seen this. When a new SARS-2 variant sweeps, it's honed its Ab-evasion skills in years of combat w/an immune system too weak to clear it but strong enough to challenge it. But in the long term, who knows? Maybe we'll see a zombie-spike sweep someday. 🧟♂️ 11/end
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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…
...and for reasons I’ll describe below, I now believe rumors of N*’s death are exaggerated.
First, XEC is in terminal decline, replaced by variants with full N* expression, so N* is back in fashion.
3/34 journals.plos.org/plosbiology/ar…
@DameSunshine @SharonBurnabyBC B.1.1.529 wasn't/isn't a real variant; it's a placeholder that represents a putative ancestor of BA.1/BA.2/BA.3.
Bad sequences and/or coinfections tend to get categorized as B.1.1.529:—they have enough Omicron muts to be ID'd as Omicron but so much dropout/mixed signals...
1/
@DameSunshine @SharonBurnabyBC ...that a specific designation isn't possible. Travel sequencing in the US is done by Ginkgo Bioworks. Their sequences are generally poor quality & they upload *pooled* sequences—against database guidelines. The B.1.1.529 here are likely low-quality/pooled sequences from GBW.
2/
@DameSunshine @SharonBurnabyBC I think it's entirely possible that a new, divergent variant will emerge this summer. There are hints with BA.3.2 & a 50-spike-mutation BQ.1.1 that has transmitted at least once. Other similar chronic infection-derived variants are undoubtedly lurking all over, unsequenced.... 3/
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
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
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…
About 1 month after this monster BQ.1.1 appeared, an even more extreme sequence has shown up in Alberta. Like the BQ, it has 50 private spike mutations, but it also has >40 AA mutations elsewhere in the genome. 1/6
They include the full panoply of NSP3, NSP12, & N muts I've written about previously. ORF1a:S4398L is the most common mutation in the 4395-4398 region, this has ∆S4398, a rarity also seen in a few other extremely divergent seqs w/this constellation. 2/6
In a theme that's become familiar, it's added two spike NTD glycans, N30 (via F32S) and N155 (via S155N+F157S).
Another chronic-infection leitmotif (first noted by @SolidEvidence): reversions to common or consensus residues in related Bat-CoVs, including SARS-1. 3/6
A fascinating SARS-CoV-2 sequence was recently uploaded—collected from a dog in Kazakhstan in July 2022.
Usher places the seq 1 nuc mut from the Wuhan ref seq—C21846T/S:T95I—i.e. pre-D614G. Could this seq somehow have a close connection to the first days of the pandemic?
1/19
Of the sequences near this one on the tree, all are low-quality & clearly bad BA.1 or Delta sequences. The only genuine one is from the UK, collected April 2020. So it's likely even S:T95I was not inherited.
This sequence has several fascinating aspects. 2/
(This all assumes the sequence is accurate and that C241T & C14408T (ORF1b:P314L) are genuinely absent. Its mutational characteristics make me certain this is a good sequence, though it's not impossible there's dropout not indicated hiding C241T and/or C14408T.) 3/
Do you remember BA.3—the weakling cousin of BA.1 & BA.2 that seemed to take the worst from each & had weaker ACE2 binding than even the ancestral Wuhan Virus?
After 3 years, BA.3 is back.
And it is transmitting.
Who saw this coming?
1/13
While the full extent of the new BA.3’s spread is not known, it’s been detected in 2 different South African regions through regular (not targeted) surveillance by @Dikeled61970012, @Tuliodna, & the invaluable South African virology community.
2/13 github.com/cov-lineages/p…
After nearly 3 years of intrahost evolution in a chronically infected person, the new BA.3 is almost unrecognizable. It has ~41 spike AA substitutions (4 of which are 2-nuc muts) to go with 14 AA deletions (∆136-147+∆243-244). We’ve seen nothing like this since 2023.
3/13