Thread by @TRyanGregory

Is SARS-CoV-2 running out of evolutionary space? Is variant evolution slowing down? Is immune escape unlikely anymore? Let's explore. 🧵

Here are some phylogenies (evolutionary trees) of the major SARS-CoV-2 variant lineages from . One is in radial format, the other unrooted, but they show the same information and are both scaled to divergence (number of mutations). nextstrain.org

And here are some plots of mutations over time, again from . There is no sign of this rate of accumulation of mutations slowing down (if anything, more recent variants are above the trend line). nextstrain.org

It's worth looking at spike (S1) mutations specifically. Note two things here:

1) We're still getting a LOT of new mutations.

2) These come in rather discrete jumps, then a flatter plateau. That's because of recombination or within-host evolution in persistent infections.

Here is some info on immune escape and ACE2 binding -- that is, how well the variant avoids existing antibodies and how well it can attach to the receptors on our cells. The top right is the "uh oh" zone where it is good at both. From . nextstrain.org

Looking at global trends for immune escape and ACE2 binding for the last 20 days, we see lots of variants with very high immune escape compared to BA.2, and some that also have high ACE2 binding. Note the change between BA.2.86 (circled) and its descendants. From @RajlabN.

Here's immune escape (vs. BA.2) over time, from . Again, the virus is not running out of ways to escape current immunity (which is partial, temporary, and changing according to vaccinations and infections). From . nextstrain.org
nextstrain.org

Why does this keep happening, contrary to minimizer assumptions? Because:

1) Orgel's second rule: "Evolution is cleverer than you are".

2) This:

A reminder about Greek letters and the decision to keep calling everything "Omicron".