Is SARS-cov-2 evolution inevitable?

On Friday I had a very interesting chat with Jesse Bloom about his work that showed the mutations the coronavirus can acquire to evade antibodies and, perhaps, ultimately the immune response.

Jessie showed that the virus can escape individual antibodies, probably natural immunity and even vaccine-induced immunity (in the worst case leading to a common-cold or flu like cycle of re-infection). However, whether widespread use of vaccines will actually encourage these “escape mutations” by selecting for resistant viruses, or actually prevent them from evolving, according to Jessie, is not yet known. It may depend on how fast we can get people vaccinated and keep the pandemic under control while we do. Unlike the coronaviruses that cause common colds and are constantly circulating, the first SARS epidemic in 2003 never really got going. Maybe, despite similar molecular mechanisms to SARS-cov-2, that virus couldn’t adapt fast enough and went extinct.

But how can virus evolution be slow? When we actually compare the changes in viral evolution to the ones that could have occurred, evolution of viruses seems to be mutation limited. Surprisingly, viral populations do not appear explore the fitness landscape effectively and are “waiting” for mutations to help them evade the immune system and drugs. This is something I stumbled across a few years ago with Maria when we were trying to predict the evolution of HIV resistance (check out the last chapter of her thesis). At first, this is very surprising given the large numbers of viruses in each person, Jesse explained that viruses probably experience very strong stochastic bottlenecks during transmission. This means that the effective population size of viruses might be closer to the infected host population size, rather than the number of viral particles. Natural selection isn’t nearly as effective as we might expect.

This would explain why these viruses appear to evolve so slow despite their short generation times and high mutation rates. At the population level, viruses can only start adapting efficiently once they have infected a lot of hosts. This explains why we only started seeing easily “accessible” beneficial mutations in the coronavirus after half a year into the SARS-cov2 pandemic: although the numbers of people infected seems like a lot, the effective population size is still pretty small on the population genetics scale (compared to, say, drosophila). Once the numbers of infections get high enough and there is a large enough virus population, only then do we actually see natural selection at work, and new strains evolve to escape the immune system.

If true, this means that the evolution of immune and vaccine escape mutations in SARS-cov2 might not yet be inevitable. If we can “roll out” the vaccines fast enough, maybe we can reduce the viral population size enough to stop evolution.

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