What do the new SARS-CoV-2 mutations mean, and how should we track them

In the past three months global attention has turned to the discovery and relative global health risks of new variants of the SARS-CoV-2 virus. News today suggests that a new covid variant, B1525, has been identified in the UK. In December, the discovery of what has become popularly known as the “Kent variant,” or to give it’s proper name B.1.1.7, led to a virus sweeping across the United Kingdom and dominating infections due to an increase in transmissibility. This was followed by the “South African” variant B.1.351, which contains a mutation now being reported to reduce the efficacy of the ChAdOx vaccine to the extent that South Africa are removing the vaccine from their vaccination programme. The “Brazil” variant P.1 is also spreading to multiple countries with worries about its propensity for causing re-infections, given its emergence in a place that may have already hit herd immunity in the first wave. 

The world now seems obsessed with SARS-CoV-2 variants and designating them with a place of origin. This is an unfortunate stigma that should be avoided at all costs given that where a virus is first detected is not necessarily where it originated. Lest we forget, Spanish Flu (the 1918 Influenza pandemic) had absolutely no connection to Spain.

The obsession with variants is now becoming as contagious as the virus, and unfortunately it also provokes similar knee jerk reactions. The discovery of the B.1.351 variant in the UK has led to a mass scale targeted testing (surge testing) and sequencing regimen in affected areas in an attempt to control its spread. This is due to a press release statement that the ChAdOx vaccine did not protect against mild and moderate covid-19 symptoms in a very small South African study of young adults. While prudence and quick action should always be advised in matters of Covid, it is also worth remembering that none of the data are published and so a significant supposition is being made on the ability of the Oxford AstraZeneca vaccine to control B.1.351 cases. Borders are now being closed in efforts to prevent numerous introductions of new variants of concern into the UK and other countries, but will this truly protect us from new SARS-CoV-2 variants?

What makes the variants a concern is not where they come from, but the mutations they contain. The B.1.1.7 virus is characterised by a deletion in the spike protein and a mutation at N501Y which enhances its transmissibility, as well as a potentially important mutation in the furin cleavage site. These mutations are found on a background of an unusually high number of other mutations making B.1.1.7 distinct. In the case of B.1.351 the key mutation which makes it a threat to vaccine efficacy is the E484K mutation in the spike protein, also seen in P.1. However, it is incredibly naïve to think that these mutations of concern are restricted to singular geographically defined viral lineages.

What has driven the emergence of these phenotypically important mutations are significant selection pressures. In the case of B.1.1.7, random mutations conferring an increase in transmissibility led to an increase in fitness of the virus which was rapidly selected for and became dominant in the UK. In the case of B.1.351 it may be that selection is for a random mutation allowing some form of enhanced escape from immune pressure and onward transmission, generating a fitness advantage—although evidence remains weak for this. The key salient point here is that these selection pressures are not geographically specific. The virus is encountering similar selection pressures wherever it is transmitting and has relatively high prevalence, meaning that the selection for random mutations that can confer a fitness advantage can happen anywhere, and at any time. This is now being seen with the emergence of the E484K mutation in the B.1.1.7 virus variant, meaning that the “Kent” variant now has the important “South Africa” mutation.

The evidence of multiple introductions of SARS-CoV-2 into the United Kingdom over the course of 2020 is compelling enough to lead to a much stricter policy of border control and monitoring of incoming travellers for the virus. Indeed, this is a measure that should have already been in place in 2020 and not only in February 2021. However, the need for near real-time testing and genomic surveillance goes way beyond introductions from travel or targeting areas where B.1.351 has been found. 

The speed and success of the UK vaccine policy, new and strong selection pressures are being imposed on SARS-CoV-2 all across the country. It is possible, maybe even likely, that this will lead to selection of new mutations and the emergence of new variants within this country. What we need now is the ability to match our testing capability with a rapid genotyping and/or sequencing capability, with some form of genotyping applied in real-time to positive samples. This would allow the kind of real-time epidemiology that serendipitously occurred with B.1.1.7 due to the effect on the S gene target amplification of the Thermo Fisher PCR assay used in many of the pillar 2 testing labs. The closer this genotyping or whole genome sequencing can happen to the testing, the quicker the data can be used and actioned. 

Alan McNally is professor in Microbial Genomics at the University of Birmingham

Competing interests: I am the director of a Pillar 2 testing lab based at University of Birmingham