BA.2 continues to do its thing in Denmark. The two most recent days of sequencing (January 20 & 21) recorded 74.2% BA.2 (285 of 384 cases). 1/9
The exponential increase in the proportion of BA.2 cases continues in the UK.
The apparent slowdown in growth in the past several days is entirely due to 0 of 8 sequences being BA.2 over the past four days & should therefore be ignored. 2/9
Similar exponential increase in the percentage of BA.2 cases in the US.
Again, the illusory plunge over the last five days is entirely due to a very small number of sequences and should be ignored. 3/9
My home state of Indiana had recorded zero BA.2 cases before last night's update, when six cases were recorded in the most recent week of sequencing, indicating a substantial percentage of BA.2. Major caveat: sample size very small. 4/9
Germany's BA.2 path is similar to what Denmark's was early on. A recent report found that 30% of cases in Berlin were BA.2, so as has been the case elsewhere, large cities with lots of international travelers are leading the way. 5/9
Japan finally has enough BA.2 to provide a decent indication of it's path. Surprise!—it's upward.
(Once again, the tiny sample sizes in recent days mean the illusory plunge at the end should be ignored.) 6/9
Not much sequencing in Portugal, but in the most recent day of sequencing, which was two weeks ago, all eight cases sequenced were BA.2. 7/9
Spain, like Portugal, has poor genetic surveillance, but is seeing a similarly steep rise in BA.2.
Small sample size makes this a pretty unreliable estimate, however. 8/9
Most of the other countries whose graphs I posted in a previous BA.2 update have seen little change. Not much has changed in Sweden, but I'll include it here since it has among the highest level of BA.2 among countries with decent sequencing. 9/9
I was rushed when putting together this thread and made a mistake in the number of BA.2 cases recorded in Indiana. There have actually been 12 BA.2 sequences in the most recent 8 days of sequencing, not 6. This gives Indiana the highest percentage of BA.2 of any US state.
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@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-…
@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 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
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
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
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
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
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
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.
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