Ryan Hisner Profile picture
Dec 14, 2021 6 tweets 3 min read Read on X
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?

Dec 6—3%
Dec 7—7%
Dec 8—13% Image
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… Image
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-… Image
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." Image
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. Image

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More from @LongDesertTrain

Nov 24
@SolidEvidence There was yet another paper this week describing someone chronically infected, with serious symptoms, but who repeatedly tested negative for everything with nasopharyngeal swabs. On bronchoalveolar lavage (BAL), they were Covid-positive. 1/ ijidonline.com/article/S1201-…Image
@SolidEvidence BAL is very rarely performed, yet there must be dozens of documented cases now where NP-swab PRC-negative patients who were very ill tested positive by BAL. This has to be way more common than we realize.

If we had a similar GI test, I imagine we'd find something similar. 2/
@SolidEvidence Importantly, the patient was treated and improved, likely clearing the virus for good. Many, maybe most, chronic infections could be treated and cleared. But they have to know they're infected for that to happen. 3/
Read 4 tweets
Nov 22
Superb thread here by @jbloom_lab that meshes well with what we've seen over the last few months in SARS-CoV-2 spike evolution: not much.

IMO, nothing significant has happened since the NTD-glycan-adding muts (T22N, ∆S31) & Q493E appeared. This 🧵 explains why. 1/6
Read full 🧵for explanation, but the short story is that the best apparent escape mutations all interact w/something else—like a nearby spike protomer or other important AA—making mutations there prohibitively costly.

In short, the virus has mutated itself into a corner. 2/6
It's very hard to effectively mutate out such a local fitness peak via stepwise mutation in circulation since multiple simultaneous muts might be required to reach a higher fitness peak. 3/6

Read 6 tweets
Nov 10
It's an interesting thought. I think the evidence is strong that all new, divergent variants have derived from chronic infections. The first wave of such variants—Alpha, Beta, Gamma—IMO involved chronic infections lasting probably ~5-7 months. It's controversial to say.... 1/15
…that Delta originated in a chronic infection, but I think the evidence that it did is strong. One characteristic of chronic-infection branches is a high rate of non-synonymous nucleotide (nuc) substitutions (subs)—i.e. ones that result in an amino acid (AA) change. 2/15 Image
For example, if 80% of nuc subs in coding regions cause an AA change, that’s a very high nonsynonymous rate. The branch leading to Delta has 17 AA changes—from just *15* nuc subs! That’s over 100%. How is this possible? 3/15
Read 15 tweets
Nov 3
I'd add that XEC's had no noticeable impact on cases & isn't likely to going forward barring a serious change, which we've not seen since S:Q493E & the glycan-adding S:S31-/S:T22N appeared months ago. Next major change seems likely to take the form of an entirely new variant. 1/4
I've been in lockstep with @SolidEvidence and @JPWeiland on this front. Despite the sensational early growth advantages XEC appeared to have, it never seemed likely to me ever to have a noticeable real-world impact. 2/4
In fact, XEC resembles BA.5.2 + ORF1b:T1050N, which had a similar growth advantage in summer 2022. That one, however, never had a sexy name like "XEC" that was distinct from other major contemporary variants so it passed unnoticed. Names matter. 3/4
Read 4 tweets
Oct 11
Molnupiravir-created mutants still show up intermittently, mostly in Australia and Japan. A remarkable one popped up today: A KP.3.1.1 with 94 private mutations. 1/6 Image
The closest related sequences are from the same region and from about 1 month earlier, suggesting these 94 consensus mutations were acquired in about one month, and possibly a shorter period of time. 2/6 Image
It has the classic MOV signature of an extremely high percentage of transversions, primarily C->T and (especially) G->A.

93/94 mutations are transitions
27/94 are C->T
38/94 are G->A

More detailed discussion of this in 2022 thread below.

3/6
Read 6 tweets
Oct 5
There aren't many convergent mutations in ORF1b in chronic-infection sequences. But many of the ones that do show up repeatedly are also highlighted in this study looking at NSP12 mutations that developed in immunocompromised pts treated with remdesivir. 1/4
I've spent hundreds of hours compiling a list of >3500 likely chronic-infection sequences & have created an imperfect, approximate measure for how overrepresented a mutation is in chronic sequences compared to circulating sequences (as measured by independent acquisitions). 2/4
Of the top 10 ORF1b chronic-infection-specific mutations on this list (occurring ≥5 times), five appeared in the remdesivir-treated patients in this study: Q435K, C455Y, V783I, M785I, & C790Y.

V783I was in 2 study patients & is also the most common of these in chronics. 3/4 Image
Read 5 tweets

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