Thread by @TRyanGregory

A bit about the two levels of viral evolution and BA.2.86. 🧵

BA.2.86 (Pirola) recently switched from evolving within a single host (someone with a long-term infection) to being transmitted among hosts. What evolves within a host is different from what evolves among hosts.

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Within a host, there will be a "swarm" or "quasispecies" of slightly different versions of the virus (because the host was infected by more than one version and/or due to mutations happening in viral lineages within that host).

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Whether a random genetic error (mutation) is fit or unfit depends on the environment. The mutations that confer an advantage within hosts are often different from those that are advantageous among hosts in a population with significant existing immunity.

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The first Omicron (B.1.1.529) evolved within a host and then re-entered the broader population and took off. However, (partial, temporary) population immunity resulting from vaccination and prior infection then (in late 2021/early 2022) was not what it is now in summer 2023.

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Since the first Omicron, there have been both large waves or "tsunamis" (BA.1, BA.2) and then sustained high baselines or "high sea level" (BA.5, BQs, XBBs). In other words, a *lot* of infections with a variety of "Omicron" variants.

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So, BA.2.86 is moving from within-host evolution to among-host evolution in a very different landscape of both host immunity and existing variants than the first Omicron encountered. Now, there is a population that has a lot of past exposure to "Omicron" infections.

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There are also large numbers "Omicron" variant lineages circulating that have been evolving in this among-host environment for a long time. In their case, what has been under selection is immune escape and transmissibility. That's not what is under selection within a host.

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The BA.2.86 lineage appears to have become established to some degree in the global host population. It would be surprising if it were able to immediately outcompete everything else that has been evolving in that environment for a long time. However...

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... now there is selection on BA.2.86 and its descendants for transmissibility, immune escape, ACE2 binding, etc.

We now have a highly mutated and at least partially successful lineage as the starting point for additional evolution in the host population.

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My concern is not so much that stock BA.2.86, fresh out of within-host evolution, will be able to outcompete the dominant XBBs. My concern is that its descendants might. Or that there may be recombination between BA.2.86 and XBB lineages.

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Again, the first XBB did not outcompete existing variants at the time. It had strong immune evasion, but also weakened ACE2 binding. A couple of generations later, XBB.1.5 (Kraken) had a combination of mutations that restored ACE2 binding. It became globally dominant.

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It's important that we continue to track BA.2.86 and its descendants -- and combinations of mutations -- and that we think about variants as evolving lineages, not as static entities.

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