When the virus replicates, it makes errors in its viral RNA. These errors are called mutations. Viruses with one or more of these mutations are called variants.

Some variants of concern that have a selective advantage over ancestral forms of the virus are on track to become dominant. The B.1.1.7 variant, for example, is sweeping over most of the US and India because it is more transmissible. Similarly, ‘escape’ mutations such as the E484K spike mutation, which may potentially allow people to become reinfected, have independently evolved in multiple lineages and these are increasing in frequency.

As long as the virus is allowed to spread, there is a risk that the efficacy of current vaccines will be reduced. But with ongoing genomic surveillance, forecasting virus evolution should help even better vaccine design. Genomic surveillance of SARS-CoV-2 should therefore be a priority, particularly in regions with high prevalence.

The biggest driver of coronavirus spread is susceptible hosts. An effective vaccine roll-out, particularly in areas with high prevalence, will be the best strategy for avoiding long-term spread.

​The B1.351 variant, which emerged in the last quarter of 2020, has become the dominant variant in South Africa. The P1 variant, which was first detected in Brazil in December 2020, is now the dominant variant in Brazil. The P1 variant may have emerged in Manaus, an area of Brazil where there was a high rate of previous infection from the first wave (it was estimated that 76% of the population had been infected by October 2020) but which witnessed a large second wave of infection, beginning in December 2020.

It is unclear how these variants emerged, however, given that mutations in the spike protein have emerged independently in the same or similar sites in both variants (eg E484K, N501Y) and that these mutations confer a degree of immune escape, it is reasonable to postulate that the variants have emerged under immune selection pressure.

One theory is that these mutations resulted from accelerated evolution under immune selection pressure in a persistently infected immunosuppressed host. Both the B.1.351 variant and the P1 variant show reduced neutralisation by convalescent sera (sera from people who have previously been infected by SARS-CoV-2) and, to a lesser extent, by post-vaccination sera. Therefore, these variants have a selective advantage in areas where there are high rates of preexisting immunity from previous infection (such as Brazil).

As yet, it is unclear what degree of protection vaccines might provide against infection and transmission of these variants, and whether they might have a selective advantage in vaccinated populations. Both the Janssen and Novavax vaccines have been shown to have reduced but still substantial protection against moderate to severe disease (Janssen) or symptomatic infection (Novavax) caused by the B.1.351 variant (Janssen: a decrease in efficacy from 72% to 60%; Novavax: a decrease in efficacy from 95.6% to 57%). In contrast, the AstraZeneca vaccine appears to provide no protection against symptomatic infection with B.1.351 (a decrease in efficacy from ~70% to 10.4%), although protection against severe disease can not be excluded. While the ability of sera from people who have received the Pfizer vaccine shows a reduced ability to neutralise variants, it still retains significant neutralisation activity.

I’d also add that B.1.1.17, which does not appear to be an immune escape variant, is the dominant variant in many countries around the world at present.

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Most vaccine manufacturers are already working on vaccines against the variants. These would likely be used as booster shots in previously vaccinated individuals. Whether ongoing updating of vaccines will be required will depend upon whether the virus is able to mutate further to evade the immune response. The ability of the virus to mutate its spike protein will ultimately be limited by the ability of the mutated spike protein to bind to its host cell receptor, ACE2.

Some vaccine developers are working on vaccines against other variants that might emerge in the future.

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It is now highly likely that SARS-CoV-2 will become a seasonal illness. To reduce the risk of emergence of new variants, we need to reduce the burden of infection in communities around the world, both through public health measures and vaccines.