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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Fantastic review on chronic SARS-CoV-2 infections by virological superstars Richard Neher & Alex Sigal in Nature Microbiology. I’ll do a short overview, outline a couple minor quibbles, & defend the honor of ORF9b w/some stats & 3 striking sequences from the past week.
1/64
First, let me say that this is well-written, extremely readable, and accessible to non-experts, so you should go read the full paper yourself, if you can find a way to access it. (Just realized it’s paywalled, ugh.) 2/64nature.com/articles/s4157…
Neher & Sigal focus on the 2 most important aspects of SARS-CoV-2 persistence: its relationship to Long Covid (including increased risk of adverse health events) & its vital importance to the evolution of SARS-CoV-2 variants. I’ll focus on the evolutionary aspects.
3/64
In SARS-2 evolution, amino acid (AA) mutations get the lion’s share of attention—& rightfully so, as noncoding & synonymous nucleotide muts—which cause no AA change‚ are mostly inconsequential. But there are many exceptions, including a possible new one I find intriguing. 1/30
I’ll discuss four categories of such “silent” mutations, two of which might be involved in the recent growth of one synonymous mutation.
Maybe the single most remarkable example of convergent evolution in SARS-CoV-2 involves noncoding mutations: the multitude of muts in major variants that have pulverized the nucleocapsid (N) Kozak sequence.
I wrote about this below & a few other 🧵s 3/
@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