Taking all this together, we expect SARS-CoV-2 will continue to cause new epidemics, but they will increasingly be driven by the ability to skirt around the immune system. In this sense, the future may look something like the seasonal flu, where new variants cause waves of cases each year. If this happens, which we expect it will, vaccines may need to be updated regularly similar to the flu vaccines unless we develop broader variant-proof vaccines.

And of course, how much all this matters for public health depends on how sick the virus makes us. That is the hardest prediction to make, because evolution selects for viruses that spread well, and whether that makes disease severity go up or down is mostly a matter of luck. But we do know that immunity reduces disease severity even when it doesn’t fully block infections and spread, and immunity gained from vaccination and prior infections has helped blunt the impact of the Omicron wave in many countries. Updated or improved vaccines and other measures that slow transmission remain our best strategies for handling an uncertain evolutionary future.