About that BA.2.86 COVID variant

There has been some head-scratching about the recent COVID variant, BA.2.86, which has 34 amino acid changes in the spike protein compared to its closest reference sequence. A commenter over on angrybear.com blog asks: “how can one virus suddenly wake up one morning and find it had mutated 30 times overnight? And that all 30 of its mutations were viable? ..it’s difficult for me to understand how such a major change could have possibly occurred as part of what should naturally be a slow-moving evolutionary process…”

Let’s unpack this comment, since I think doing so can clarify virus population biology, how variants arise and what they mean.

First of all, we’re not talking about “one virus” acquiring 34 mutations “overnight.” It is estimated each infected person carries 10^9–10^11 SARS-CoV-2 virions* during peak infection and that the genetic diversity of virions in an infected host covers all possible single nucleotide substitutions. So the BA.2.86 variant emerged from an immense, evolving population. What likely happened is that BA.2.86 arose from a chronically infected host who harbored orders of magnitude more virus particles over the course of infection than would be carried by most people. This could be someone who is immunocompromised, either by age, disease or medication, and thus (a) was delayed in clearing the virus and (b) wasn’t providing strong immunological selection. So what happened over time (timespan of weeks, not geological time) is that sequence changes accumulated in the population of virus particles, one family of which emerged as BA.2.86.

Secondly, a useful distinction can be made between “variants” and “mutations.” Those 34 differences are probably not all functionally significant—some are probably neutral, both for virus entry and for immunogenicity.In the event, it looks like there might be less than meets the eye in the case of BA.2.86:

“Two independent labs have basically shown that BA.2.86 essentially is not a further immune escape compared with current variants,” Dr. Dan Barouch, director of the Center for Virology and Vaccine Research at Beth Israel Deaconess Medical Center and leader of one of the labs, told CNN.

“Their results align with earlier experiments by labs in China and Sweden. Taken together, the data suggests that BA.2.86 will not be as troublesome as experts had feared. In short, this one seems to be a “scariant.””

* for comparison, it is estimated that the total number of humans that have ever lived is 117 billion, or 1.17x10^11, and the coronovirus genome is a tiny fraction of the size of the human genome.

https://www.cnn.com/2023/09/03/health/covid-new-variant-pirola-early-lab-results/index.html