Over the past nine months I've written occasionally about the prospects for the SARS-CoV-2 virus to evolve into a less (or more) virulent form.

In general, we can't count on decreasing virulence, various folk theories about "viruses evolve to become more mild" notwithstanding.

Another important aspect of viral evolution is the evolution of escape mutants—strains that avoid existing immunity by changing the structure of key immune targets.

In the *short term*, I haven't viewed this as a huge concern.

The structure of the SARS-CoV-2 genome is very different from the segmented flu genome. Standing diversity is comparably low, production of new diversity is limited, and SARS-CoV-2 lacks the rich pool of recombinational sources from a range of host species that influenza enjoys.

But as immunity increases in the human population due to natural infection or successful vaccination campaigns, selection for escape variants intensifies.

A new paper (h/t @BillHanage) details one potential escape variant. https://www.biorxiv.org/content/10.1101/2020.11.04.355842v1

I don't foresee COVID ever posing the strain prediction challenges that flu does, but as we move toward broader community immunity, we are going to need to keep an eye on standing genetic diversity and immune responses to that diversity.