Ryan Hisner Profile picture
Dec 24, 2021 6 tweets 3 min read Read on X
1/6 At a private gathering of 33 Pfizer-triple-vaccinated health care workers in the Faroe Islands, 21 were infected with Omicron—a superspreading event among 3-dose-vaccinated people. All received dose #3 within 2.5 months of the event. Very discouraging.
medrxiv.org/content/10.110…
2/6 All participants tested negative within 36 hours of the event: five with rapid tests and the other 28 with PCR tests. Median age was 45. Only four of the 21 infected had any comorbidities.
3/6 And very similar to the Oslo Christmas superspreader event (where 79 of 80 infected were symptomatic, with 74 having >3 symptoms), all 21 experienced symptoms. There is virtually no asymptomatic infection with Omicron it seems.
4/6 While most had mild illness, moderate and severe symptoms were not as rare as one would hope in a group of young, healthy, triple-vaccinated individuals. Thankfully, none were hospitalized.
5/6 As seen in the Oslo superspreading event and described anecdotally elsewhere, the incubation period was short: 3.24 days on average. Five of those infected still had symptoms at the time of their interview (12-14 days after infection).
6/6 CDC messaging has consistently downplayed the risk of transmission among the vaccinated, & it needs to stop. These people did everything right: they were triple-vaxxed & all tested before gathering. It didn't matter.

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More from @LongDesertTrain

Jun 18
. @BenjMurrell is doing the best variant growth modeling in the world, & his latest results confirm most of what we've thought: KP.3 is the fastest large variant, & its sublineage KP.3.1.1—w/the highly advantageous, glycan-creating S:∆S31—is easily the fastest in the world. 1/15
It can be a difficult to decipher the meaning of these graphs if you don't have an encyclopedic knowledge of the latest variants—which I think only @siamosolocani possesses—so I tried to add some context to Ben's graph, which I'll explain below. 2/15 Image
I divide key mutations into 4 categories, from most to least impactful, IMO.

#1. Q493E (KP.3 exclusive), F456L (~universal)
#2. T22N, ∆S31 (glycan-adding)
#3. R346T, T572I
#4. F59S/L, S60P, K182N, Q183H

Lowest row of boxes on the graph is group #1, above it #2, & so on. 3/15 Image
Read 16 tweets
May 8
KP.3 (w/the rare Q493E) has been my pick since I first noticed it emerging from numerous travel seqs from India. F456L & R346T are the typical stepwise immune-evasion mutations that, as @shay_fleishon noted, very likely impose a fitness cost. Q493E may be different. 1/
Q493E involves the rarest of all nucleotide mutations, C->G, and occurs at a key residue that we've seen very little action from of late. 493 mutations, however, are common in the Cryptics, usually Q493K I believe. (@SolidEvidence can correct me if I'm wrong on that). 2/8 Image
493 is also one of the few residues where mutations—on BA.1/BA.2 backgrounds—can confer large increases in ACE2 affinity—see @jbloom_lab data below. The 2-nuc Q493A & Q493V appeared in a handful of remarkable chronic-infection seqs, for example. 3/8 Image
Read 8 tweets
May 1
We have a new record for mutations in a non-molnupiravir sequence. It's a BA.2.12.1 with >100 private mutations. There are 4 seqs from early April, all from the same patient. I'll discuss four interesting features it has in this 🧵. 1/23 Image
#1) Reversions
Reversions are extremely rare. They almost never appear in circulating lineages. There are, however, a large number of reversions that are convergent in chronic-infection sequences. This one has more than usual. 2/23 Image
Let's start with my favorite.
• ORF1b:L314P (NSP12_L323P)
The extraordinarily rare yet hugely significant ORF1b:L314P reversion is an enigma. ORF1b:P314L was one of the very first SARS-CoV-2 mutations. It quickly dominated & has been universal ever since. 3/23
Read 23 tweets
Apr 19
What connects two regions on opposite ends of NSP12, a narrow slice of an obscure NSP3 region (DPUP/SUD-C), & a 3-AA sliver of nucleocapsid (N)? I have no idea, but I’m convinced there’s a link that could help reveal the inner workings of SARS-CoV-2. 1/120
Image
Image
I previously wrote a thread about the strange connection between ORF1a:4395-4398 and ORF1b:820-824 (NSP12_3-6 & NSP12_829-833). There is no known connection between these regions, & they are not close to each other in the NSP12 protein structure. 2/120
Mutations in both regions are rare, yet they arise in the same sequences again and again, at rates that cannot be coincidental. Furthermore, there have never been any circulating lineages with these paired mutations—they are a chronic-infection specialty. 3/120 Image
Read 124 tweets
Apr 13
Always nice to run across a possible function of a rare mutation that's shown up in multiple chronic-infection SARS-CoV-2 seqs. Thanks to an excellent paper by @TheMenacheryLab & @J_Paul_Taylor, I think I now know why N:L13P (a reversion) shows up. 1/6
They proved that the N:1-25 region, esp. the ITFG AA motif from N:15-18, is the essential element in N's ability to suppress the formation of stress granules (SGs) in cells, which capture & disable long viral RNAs & help organizing innate antiviral immune responses. 2/6
Image
Image
All variants retain the ability to suppress SGs, but Omicron's N:P13L weakens N's binding to G3BP1/2—the master cellular regulators of SGs—by about 2.3-fold. That's pretty slight, & almost certainly not enough selection pressure to result in reversions in circulation... 3/6 Image
Read 7 tweets
Apr 4
BA.2.86, a clear chronic infection-derived variant, has obtained near-total global dominance in the form of JN.1. This may have squeezed out any room for new CI-derived variants to take hold & spread, but they're still out there. A recent one had ~38 private spike mutations. 1/5
BN.1.3 is a BA.2.75 descendant that emerged in Aug 2022, but much older variants still exist.

Alpha, for example, has disappeared from circulation, but it's not extinct—it's still evolving within an unknown # of hosts. On rare occasions, we catch a glimpse of this. 2/5 Image
More frequently, though, we see BA.1-derived chronic-infection sequences. There's been no obvious slowdown in the appearance of highly mutated, chronic-infection BA.1 sequences. This most recent one had ~75 private nuc substitutions. 3/5 Image
Read 5 tweets

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