Fri 2022-Sep-23

New SARS-CoV2 Variants… Again!

Tagged: COVID / JournalClub / PharmaAndBiotech / Sadness / SomebodyAskedMe

Tired of COVID-19? Me too. But… apparently the SARS-CoV2 virus is not yet tired of us!

Yet More Variants

From the indispensable Eric Topol, of the Scripps Research Translational Institute, comes some timely if unwelcome news about variants and convergent evolution of the COVID-19 causing virus SARS-CoV2:

Topol @ Twitter: SARS-COV2 evolutionary path with convergence of several mutations

US CDC COVID-19 Data Tracker: Variants as of 2022-Sep-23 He’s quoting the nowcast data from the US Centers for Disease Control and Prevention’s COVID-19 Data Tracker. [1] We’re looking at the variants of concern (VoC’s) as of the first week of 2022-Sep, reproduced here.

Now, there’s a lot to say about these data. However, for me (and apparently for Topol) the important bit is the recent change in proportions of infections by the various variants:

  • When you look back at mid-summer in the US, the main variants were Omicron/BA.4 and Omicron/BA.5. Really, mostly BA.5 – probably the variant that we caught here at Chez Weekend this summer. The rest of all the variants were being outcompeted, and vanishing.
  • Then we saw Omicron/BA.5 outcompete Omicron/BA.4, to become the dominant strain.
  • But now look at the last few weeks: Omicron/BA.5 is itself being outcompeted by something even more vicious! It looks like Omicron/BA.4.6 is on the rise, slowly taking over.
  • The table on the right gives the quantitative proportions of each VoC, along with the 95% confidence intervals for telling us the uncertainty.

Yes, it doesn’t look like much… now. That’s how exponential growth works: nothing, nothing, nothing much, not really important yet, … and suddenly… yow!

SARS-CoV2 lineage: 'convergent evolution on steroids' So where did this Omicron/BA.4.6 monster come from? For that, we consult virology professor Marc Johnson, who collected the evolutionary lineage data shown here, as a directed acyclic graph.

The Omicron/BA.2 root at the right is where all this Omicron variant nastiness started. (OK, there were others like BA.1, but they didn’t amount to as much.) As you move to the right in the diagram, the spike protein acquires more mutations, noted on each arrow in the usual amino acid substitution notation. The result is a directed acyclic graph, because the variants each contain a subset of the accumulated mutations (hence a subgraph of the subset DAG).

So we see that Omicron/BA.4.6 is just Omicron/BA.4 with an additional R346T amino acid substitution.

It still amazes me, after all these years, that this is all it takes: just a little tweak, and suddenly you have a more aggressive virus. Biology is weird.

This diagram also warns us that Omicron/BF.7 and Omicron/BE.1.2 are in the same vicinity, mutation-wise, and it’s worth keeping an eye on them. Omicron/BF.7 is in the CDC data above, albeit at low levels, but growing.

The Weekend Conclusion

No, it’s not over.

As soon as we’ve cleared the 2-3 month interval from our summer COVID-19, we’re getting the bivalent booster here at Château Weekend. Let’s hope the BA.4-5 spike mRNA is homologous enough to BA.4.6 to grant further immunity!

Happy autumnal equinox, I guess…

Notes & References

1: US CDC Staff, “Variant Proportions”, US CDC COVID Data Tracker, retrieved 2022-Sep-23.

Published Fri 2022-Sep-23

Gestae Commentaria

Weekend Editor, Sun 2022-Oct-02 01:32

Yes, the more prominent one people are worried about right now is Omicro/BA.2.75.2, as mentioned by Topol above.

The variants won’t stop until we do something like a pancoronavirus vaccine or a nasal mucosal vaccine that stops infection, and get near-universal adoption around the world.

A daunting task!

Weekend Editor, Sat 2022-Sep-24 21:33

Very interesting, thanks!

I wonder why Johnson, who did the graphic above of mutation subset relationships, didn’t say much about BA.2.75.2’s immune evasion?

Also, if BQ.1.1 really does evade both evusheld and bebtelovimab, then we’re left with no effective antibody therapies whatsoever. I really, really do not like that thought.

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