1/6 Imagine that: Omicron is undergoing phenomenally fast exponential growth in the US, just like in the UK, Denmark, and South Africa. Crossing the Atlantic didn't impair its transmissibility. Who could've guessed?
2/6 Take it from the master himself, Trevor B: "There is an inevitable very large wave of Omicron. It's going to happen." nytimes.com/live/2021/12/1…
3/6 There's such an air of fatalism around all this, as if we are utterly incapable of doing anything that could dampen or avert a devastating Omicron wave. Hospitals are already at max capacity in many states. An Omicron tsunami approaches, & we collectively shrug our shoulders.
4/6 Epidemiologist @sanghyuk_shin of UC Irvine: "We need to take this seriously, starting now. If we have learned anything on how this virus operates—it’s that any kind of mitigation, the earlier the better...." voiceofoc.org/2021/12/local-…
5/6 "...There is really no evidence that suggests that Omicron is going to be mild, there’s no evidence that it is less virulent."
6/6 At a company Christmas party at an Oslo restaurant, 80 out of 111 young (ages 30-50), 2-dose vaccinated Norwegians were infected with Omicron. Only 1 of the 80 was asymptomatic (none hospitalized). I've never heard of an asymptomatic rate so low. It doesn't suggest mildness.
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• BA.2.87.1 - Appeared suddenly Sept 2023, spread across South Africa, & was detected in WW in Thailand. Then basically disappeared after Dec 2023 (apart from 1 seq collected in May 2024 from Eswatini). Emerged just when JN.1 was sweeping—bad timing. 2/
• BA.2.83 - One of several BA.2 saltation variants that emerged in late 2022. First appeared in India, then in Denmark, Canada, and Australia. Could not compete with BA.2.75 and BA.5 though and disappeared without making any real impact. 3/
A mysterious, unusually diverse saltation lineage descended from KP.3.1.1 (last seen early 2025) has circulated at a low level for ~8 months in Ontario (see 🧵on next post).
Seemed a local anomaly, but @solidevidence just spied a weird spike in NYC WW—& it's the same one!
1/14
Wildly diverse branch of MC.10.1.7 (KP.3.1.1 descendant, died out early 2025) in Ontario.
It's apparently been circulating at a low level for the past year. ≥6 different people are represented here.
I think this must involve one or more chronic infections + transmission. 1/7
• Busy 630 loop: ∆621-622 + NVFQ->IFPMAE at S:641-644.
• 2-nuc muts: W452K + D839K.
• Ultra-rare S2 insertion: ins791P
M:H155N, ORF1a:R3164H, & ORF3a:255-256 deletions cluster in chronics, often w/S:D936H/Y or ORF1a:L3201P. Intriguingly, D936Y was in the last seq. 2/7
More info on this unusual branch can be found on the Github page for undesignated lineages, which Fede Gueli tirelessly and selflessly keeps up to date.
Another fantastic preprint on BA.3.2's propensity for children, this time from @yunlong_cao & co.
They not only confirm the findings of David Ho's lab (that kids have ~0 antibody response to BA.3.2) but dig into the details of exactly why kids are so vulnerable to BA.3.2.
1. Kids vaccinated before being infected have robust antibodies against BA.3.2
2. Unvaxed adults much more vulnerable to BA.3.2, esp. compared to mRNA-vaxed adults.
Read @yunlong_cao's 🧵 & very readable paper for details. 2/4
There's still one major paradox here I can't wrap my head around: countries with the highest vaccination rates & the lowest proportion of children appear—very low sequencing makes hard conclusions difficult—to have the highest proportion of BA.3.2. 3/4
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
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/
More details from this preprint. 50 is the limit of detection (i.e. zero). Nearly all kids under 7 had no detectable nAbs to BA.3.2, despite robust nAb titers against NB.1.8.1 & XFG.
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/
∆ORF78 is rare but not unheard of; it was in several late XBB variants (GW.5.1.1, FW.1.1, GE.1.2, etc) & a few branches of other variants. I've long thought these late XBB had an advantage in some population subsector, but I didn't suspect kids. 3/