I think most people studying viral evolution agree that the appearance of these variants now mostly reflects the very large number of cumulative infections that have occurred worldwide since the start of the pandemic. On average, one mutation may occur every time or every other time the virus infects a new person. Each mutation is kind of like pulling a slot machine — the chance of hitting the jackpot on any individual pull is small, but you pull millions of handles simultaneously the chances are dramatically increased. Viruses that ‘hit the jackpot’ by accumulating a set of mutations that makes them more transmissible will then increase in the population due to natural selection. As more people become immune through prior infection or vaccination, while transmission rates remain high, we may expect this sort of adaptation to continue.

Variants like B.1.1.7 may be able to ‘take over’ because they produce many more infectious particles that can spread from person to person than other variants. Some of the mutations that have arisen, especially in the spike protein, also appear to alter the antigenic profile of this protein—essentially the way the protein looks to the immune system—and may have been selected for improved viral replication in the face of the human immune response. It is important to note, however, that none of the variants studied to date can fully escape the immune responses generated in people in response to natural infection or vaccination. On the other hand, monoclonal antibody therapies are more likely to suffer large losses in efficacy due to changes in the spike protein.

SARS-CoV-2, like other RNA viruses, is constantly generating mutations as it replicates inside infected people. The reason that SARS-CoV-2 has been accumulating many more mutations during the past several months is probably related to increasing spread and transmission around the world. The more viral replication occurring in the human population, the more random mutations are generated, and the greater the chance that one of these mutations will improve infection or transmission, resulting in a new viral variant that outcompetes earlier ones. Genetic crossover between two different virus strains that infect the same cell can also generate rapid changes.

Human immunity, either from vaccination or infection, can also create conditions enabling new mutant variants to outcompete current variants; however, there are probably not enough immune persons yet to allow this kind of selection to occur. As herd immunity grows during the coming months with continued infections and increasing vaccination, we may see this kind of selection increase to the point where new strains that resist that existing immunity could be selected and replace earlier strains. This is the situation we see with influenza virus, where our immunity from past infections selects for rapid changes in the proteins targeted by the vaccine. This is why we need to be vaccinated annually with influenza virus strains predicted to be the most common during the coming transmission season.