Ryan Hisner Profile picture
Jan 23, 2022 16 tweets 7 min read Read on X
No one seems to know what BA.2 means for the world. I'm not aware of any studies on it, but I hope they come out soon. It seems apparent BA.2 will become dominant everywhere before long—as it already has in Denmark.

🧵 of graphs comparing BA.1 & BA.2 in various countries
1/16
Of all the countries with decent genetic surveillance, Denmark has the highest proportion of BA.2. 2/16
According to the Outbreak numbers compiled using @GISAID data, January 12 was when BA.2 surpassed 50% of all cases in Denmark, with 480/955 cases. 3/16
A similar conclusion was reached by @JosetteSchoenma, who's assiduously tracked BA.2 prevalence in Denmark (and elsewhere) and was pointing out its significance before anyone else. 4/16
The fact that Denmark has the highest level of Covid cases per 100,000 of any country in the world and the highest percentage of BA.2 of any country with decent sequencing data is probably not a coincidence. 5/16
The UK BA.2 numbers are far lower than in Denmark at the moment but are clearly on an exponentially increasing trajectory. It's only a matter of time before BA.2 becomes dominant there. 6/16
According to @OliasDave, BA.2 is doubling every 4 days (as a percentage of all cases) in the UK, meaning it could become dominant there in about three weeks. 7/16
Genetic surveillance outside of Denmark & the UK is far less comprehensive. The graphs therefore noisier & the trends less consistent. Still exponential increase in the proportion of BA.2 seems universal. Sweden and Norway are in the 10-15% range & exhibit similar trends. 8/16
Belgium and the Netherlands are both around 5% BA.2 with exponential increases underway. 9/16
Germany's data is pretty sparse after January 7, but there are hints of an early exponential increase in BA.2 there. 10/16
Finally, there have only been 47 sequences of BA.2 detected in the US, 17 of them in Arizona. But there can hardly be any doubt we'll see large increases in BA.2 prevalence throughout the US in the coming weeks. 11/16
Some have claimed that BA.2 is no different than BA.1 and nothing to worry about. It could turn out that way, but it seems far from certain. BA.2 has 70 mutations significantly more than the 53 of BA.1. 12/16
BA.1 and BA.2 share a set of mutations, but their mutations differ a great deal as well, both spike and non-spike. outbreak.info/compare-lineag… 13/16
One Denmark report said there was "no evidence" of increased severity from BA.2. This may turn out to be right, but it reminds me of the early declarations that there was "no evidence" Alpha or Delta were more severe. Evidence takes time to accumulate. 14/16
We can hope BA.2 won't seriously change things for the worse, but to assume it is nothing to worry about seems extremely unwise. Similar assumptions have not worked out well for us in this pandemic.

Interesting tidbit from @bicidiario here. 15/16
See this great thread by @PeacockFlu for more info on BA.2. 16/16

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More from @LongDesertTrain

Jul 7
BA.3.2 update: another sequence from the Netherlands, June 18 collection.

It belongs on the same branch as the GBW travel seq (tree gets confused by ORF7-8 deletion). Also, there are 3 artifactual muts in the GBW sequence (as usual), so the branch is shorter than it looks. Image
Bottom line, in my view: BA.3.2 has spread internationally & is likely growing, but very slowly. If nothing changes, its advantage vs circulating lineages, which seem stuck in an evolutionary rut, will likely gradually grow as immunity to dominant variants solidifies... 2/9
So far, this seems like a slow-motion version of what we saw with BA.2.86, which spread internationally & grew very slowly for months. But then it got S:L455S & exploded, wiping out all competitors. Will something similar happen with BA.3.2? I think there's a good chance... 3/9 Image
Read 9 tweets
Jul 2
Quick BA.3.2 update. Another BA.3.2.2 (S:K356T+S:A575S branch) from South Africa via pneumonia surveillance.

This means that 40% of SARS-CoV-2 sequences from SA collected since April 1 (2/5) and 50% collected after May 1 (1/2) are BA.3.2. Its foothold seems strong there. 1/3
2 interesting aspects of the new BA.3.2:
1. ORF1b:R1315C (NSP13_R392C)—This mut is in all Omicron *except* BA.3. So this may well be adaptive.

2. S:Q183H—First known antigenic spike mut seen in BA.3.2, not a major one, but one we've seen before—eg, LB.1/JN.1.9.2.1 2/3 Image
I think the unusually long branches in the BA.3.2 tree indicate 2 things:
1. Slow growth globally—fast growth results in many identical sequences, if surveillance is sufficient

2. Undersampling—BA.3.2 most common in poorer world regions with little sequencing of late. 3/3
Read 5 tweets
Jun 29
BA.3.2 update, Chapter: "I'm Not Quite Dead, Sir"

A new sequence from a traveler to the USA from the Netherlands was uploaded yesterday, with a collection date of June 17. 1/10 Image
This was a BA.3.2.1, the branch with S:H681R + S:P1162R (not S:K356T + S:A575S).

An updated, annotated version of the BA.3.2 Usher tree pictured below.

This sequence has the first new spike mutation since BA.3.2 emerged in November 2024—S:V227L. 2/10 Image
It has an extremely rare NSP5 mutation, ORF1a:T3487S (NSP5:T224S), only in 4 of ~17 million SARS-2 seqs

Intriguingly, 3 of these 4 share something in common w/this BA.3.2.

The first—and most remarkable—is a BA.2 from England that, like BA.3.2, has the ORF7ab-ORF8 deletion. 3/10 Image
Read 11 tweets
Jun 27
@yaem98684142 @TBM4_JP This analysis is extremely flawed.

There is nothing abnormal about BA.2.86 appearing in multiple countries shortly after discovery. This has been the norm lately w/reduced surveillance. 1/
@yaem98684142 @TBM4_JP The mutational spectrum analysis is poorly done. It cites a single study looking at the mutational spectrum in *three* immunocompromised individuals. Needless to say, this sample size is WAY too small. 3/
@yaem98684142 @TBM4_JP Furthermore, the IC people examined did not give rise to highly divergent variants with a large number of spike mutations. They appear to have accumulated a very modest number of mutations, with few substitutions in spike. The sequences themselves are apparently not published. 4/
Read 7 tweets
Jun 19
Interesting recombinant showed up today from Texas. It's a mixture of B.1.595, BA.1, and some flavor of JN.1. Most of the genome is from B.1.595. The ancestry of this one is clear: it directly descends from a B.1.595 sequence collected in January 2023, also in Texas. 1/11 Image
When the B.1.595 was collected this infection was >1 yr old, w/no sign of Omicron. BA.1 ceased circulating ~1 year prior.
Now a BA.1 spike appears w/just 5 changes from baseline BA.1, none in the RBD—S12F, T76I, Q271K, R765H, S939F.

This is a zombie BA.1 spike. 2/ Image
There are only a few signs of JN.1, & they're scattered. In ORF1a, we see JN.1's V3593F, P3395H, & R3821K, but the NSP6 deletion btwn these—universal in Omicron—is absent. In
M has JN.1's D3H + T30A & E19Q (in JN.1 & BA.1), yet A63T—also in both BA.1 & JN.1 is absent. 3/11 Image
Read 11 tweets
May 31
An awesome preprint on the novel, unsung SARS-CoV-2 N* protein came out recently, authored by @corcoran_lab & Rory Mulloy. I’ve previously written on N*’s demise in XEC, the top variant in late 2024/early 2025. But…
1/34
…this preprint, along with another great study by the @DavidLVBauer, @theosanderson, @PeacockFlu & others prompted me to take a closer look...
2/34biorxiv.org/content/10.110…
...and for reasons I’ll describe below, I now believe rumors of N*’s death are exaggerated.

First, XEC is in terminal decline, replaced by variants with full N* expression, so N* is back in fashion.
3/34
journals.plos.org/plosbiology/ar…
Read 35 tweets

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