SARS-CoV-2 Mutations Do Not Increase Transmissibility

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Electron microscopy virus visualization
[Source: CROCOTHERY/Getty Images]

A large study carried out by researchers at University College London suggests that none of the recorded mutations in SARS-CoV-2 increase its transmissibility, contrary to claims from other researchers.

Viruses all mutate over time, but some do this faster than others. Most mutations will not have a noticeable effect, but some may impact how infectious a virus is, or how sick it can make people. Coronaviruses actually have a slower rate of mutation than viruses like influenza or HIV, as they have an inbuilt enzyme that corrects ‘proofreading’ errors in the RNA when the virus replicates.

Despite this, there has been much debate and concern about whether mutations in the SARS-CoV-2 virus could make it more transmissible or more pathogenic. So far, no recorded mutations seem to have increased pathogenicity, but some research has suggested that mutations – particularly D614G – have increased the speed that the virus has spread.

“The number of SARS-CoV-2 genomes being generated for scientific research is staggering. We realized early on in the pandemic that we needed new approaches to analyse enormous amounts of data in close to real time to flag new mutations in the virus that could affect its transmission or symptom severity,” said Lucy van Dorp, Ph.D., a senior researcher at the UCL Genetics Institute and first author on the paper describing this work, which is published in the journal Nature Communications.

The UCL-based team analyzed genomic data collected from 46,723 viral samples from people with COVID-19 from 99 countries. The team used bioinformatic tools to assess viral phylogenies and evaluate whether any variants occurred more often than would be expected by chance.

“Fortunately, we found that none of these mutations are making COVID-19 spread more rapidly, but we need to remain vigilant and continue monitoring new mutations, particularly as vaccines get rolled out,” said van Dorp.

The researchers detected a total of 12,706 mutations across the 46,723 viral genomes, many of which were cytosine to uracil base changes. Of these, 398 were recurrent mutations that were candidates for increasing transmission, but they found no evidence that any of these mutations actually increased the spread of the virus including the D614G variant.

The team found that overall genetic variation across the viral samples was moderate, with an average difference of 8.4 single nucleotide polymorphisms between samples. “This low number of mutations between any two viruses currently in circulation means that, to date, we believe SARS-CoV-2 can be considered as a single lineage, notwithstanding taxonomic efforts to categorize extant diversity into sublineages,” write the authors.

van Dorp and colleagues welcome the recent positive news about the SARS-CoV-2 vaccines that are almost ready to be released for use. However, they caution that widespread vaccine use may exert an evolutionary pressure on the virus to become resistant.

“The virus may well acquire vaccine-escape mutations in the future, but we’re confident we’ll be able to flag them up promptly, which would allow updating the vaccines in time if required,” says François Balloux, Ph.D., a professor at UCL Genetics Institute and senior author on the study.

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