TOPICS: COVID-19

 

It is normal for viruses to acquire small changes in their genetic code as they are transmitted from person to person. Often these ‘mutations’ have no effect. However, because this genetic code provides the instructions for making the proteins the virus is built out of, occasionally a mutation will alter a protein’s structure in such a way that it affects how the virus behaves, for example, by making it easier for it to latch onto human cells and infect us. Such mutations may give that virus a competitive advantage over related viruses, or ‘variants’, meaning that over time, that new variant becomes the dominant one circulating in a population.

Most scientists believe that the existing vaccines being developed against COVID-19 will still be effective.

Coronaviruses mutate slower than some other viruses like influenza, however, since the start of the COVID-19 pandemic, there have been a few significant mutations which have altered the SARS-CoV-2 variants in widespread circulation. For instance, in late January or early February 2020, a mutation in the gene encoding the ‘spike’ protein for the virus, known as a D614G substitution, led to a more infectious variant, which gradually replaced the original SARS-CoV-2 variant identified in China. By June 2020, this had become the dominant form of the virus circulating globally.

Further mutations to the genetic code that produces the spike protein gene were seen in the ‘cluster 5’ variant linked to Danish mink farms, and in the new variants identified in the UK and South Africa.

Trying to reduce the number of people who become infected is also important, because mutations are more likely to occur when the virus continues to spread and to infect new hosts.

How do these new variants differ from the original coronavirus?

The variant identified in the UK, known as the B117 variant, contains 23 changes to the genetic code, relative to the original SARS-CoV-2 virus which was identified in Wuhan, China. Precisely how and where it originated is unclear, but it has since spread to become the dominant variant in London and South East England. It has also been detected in other parts of the UK, as well as in at least 31 other countries as far afield as Australia, the USA and Pakistan. Preliminary studies indicate that the B117 variant is more transmissible, but does not result in more severe disease or in people who have already had COVID-19 being reinfected. One of the mutations it contains can also affect the performance of some of the PCR tests used to detect COVID-19 infections – although most of the PCR tests being used around the globe are designed to detect several viral genes, so the impact of this isn’t thought to be significant.

The variant identified in South Africa, known as variant 501Y.V2, carries some of the same mutations as the B117 variant, but appears to have evolved separately. It also carries some different mutations. One of these, a mutation in the spike protein gene called E484K, may reduce the ability of certain antibodies from people who have recovered from COVID-19 to bind to and neutralise the virus. However, this doesn’t necessarily mean that the immune response triggered by vaccines will be less effective – something which is currently being tested. Like the B117 variant, it doesn’t appear to be associated with more severe disease, but may be more contagious than earlier variants. In both cases, more intensive public health measures may be required to control the spread of these variants.

Could these variants be present elsewhere, or could there be other variants?

Almost certainly. Many thousands of mutations have been found among isolates of the virus in various countries, with around 4,000 different spike protein gene mutations identified so far. However, the variants identified in the UK and South African have changes in their spike protein gene consistent with the possibility that they are more infectious, which is why they are generating such concern.

Both variants have been detected in numerous other countries, and may already be widespread. However, because many countries don’t routinely sequence coronavirus genomes from a large proportion of people who test positive, it is difficult to know quite how far these variants have spread – or if these variants are acquiring further mutations of concern. Stepping up global surveillance efforts should therefore be a priority.

Yet another variant has been identified in Nigeria, although details of the precise mutations it contains have not yet been published.

Will COVID-19 vaccines work against these new variants?

Most scientists believe that the existing vaccines being developed against COVID-19 – including those which have been granted emergency licences and are already being used to immunise people in various countries – will still be effective. Although the vaccines are based on the viral spike protein, the changes to its structure conferred by these new mutations are still relatively small, and the immune system is trained to recognise lots of different bits of the protein. However, it is possible that further mutations could result in the current vaccines becoming less effective, which is one reason why the World Health Organization has advised all countries to increase their surveillance of how the virus is mutating, by sampling and sequencing SARS-CoV-2 from patients.

Trying to reduce the number of people who become infected is also important, because mutations are more likely to occur when the virus continues to spread and to infect new hosts. This can be achieved through measures like physical distancing, wearing a mask, keeping rooms well ventilated, avoiding crowds, cleaning hands and coughing into a bent elbow or tissue.

If a mutation did reduce a vaccine’s efficacy, it could be relatively easy to tweak the vaccine. This is especially true for the vaccine platforms based on newer technologies such as RNA and vector vaccines, as they can be modified quickly. To enable this, scientists need to understand how the virus is mutating, and where variants carrying those mutations are distributed – another reason why ongoing global surveillance is essential.

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