Most SARS-CoV-2 mutations don’t persist or spread, but therapy-resistant variants may emerge under vaccine pressure.
An analysis of SARS-CoV-2 genome diversity in more than 1,000 people in the United Kingdom suggests that if viral mutations do arise, they can be transmitted in some cases but they rarely persist in subsequent transmissions.
“Our observations indicate the within-host emergence of vaccine- and therapeutic-escape mutations is likely to be relatively rare,” say the authors, “at least during early infection when viral loads are high.”
However, because mutations that can escape therapies like antibodies were identified, including in higher viral load samples, the authors encourage continued monitoring and vigilance, particularly as vaccines and therapeutics that put “pressure” on viruses to adapt are rolled out more widely.
Most analyses of mutations in SARS-CoV-2, the virus that causes COVID-19, to date have been focused on mutations observed in individuals that represent the dominant variants. However, new mutations are emerging in infected individuals, too, and knowledge of the full underlying diversity of viruses in human hosts — how frequently they emerge, and whether they are transmitted — is important for understanding viral adaption and patterns of spread.
Genome Sequencing Reveals In-Host Viral Variation
To better characterize diversity in single human hosts, Katrina Lythgoe and colleagues used an RNA sequencing approach to analyze 1,390 SARS-CoV-2 genomes from 1,313 nasopharyngeal swabs sampled mostly from symptomatic patients in the UK who had gotten sick between March and June 2020 (the first global wave of infection).
The authors observed only one or two variants in most individuals, but a few patients carried many variants. Most of these were lost at the point of transmission, though a small number initiated ongoing transmission and wider dissemination. Too, there were very few cases of virus transmission between households in the studied genomes.
These results suggest that during early infection, mutations that can increase the virus’s chances of escaping therapies rarely emerge and transmit. Even so, the authors did identify variants that can give the virus an advantage, including in high viral load samples. This indicates that naturally occurring variants would have the opportunity to spread as population selection pressure from vaccine rollout increases. The findings underline the need for continued monitoring, they say.
Reference: “SARS-CoV-2 within-host diversity and transmission” by Katrina A. Lythgoe, Matthew Hall, Luca Ferretti, Mariateresa de Cesare, George MacIntyre-Cockett, Amy Trebes, Monique Andersson, Newton Otecko, Emma L. Wise, Nathan Moore, Jessica Lynch, Stephen Kidd, Nicholas Cortes, Matilde Mori, Rebecca Williams, Gabrielle Vernet, Anita Justice, Angie Green, Samuel M. Nicholls, M. Azim Ansari, Lucie Abeler-Dörner, Catrin E. Moore, Timothy E. A. Peto, David W. Eyre, Robert Shaw, Peter Simmonds, David Buck, John A. Todd, on behalf of the Oxford Virus Sequencing Analysis Group (OVSG), Thomas R. Connor, Shirin Ashraf, Ana da Silva Filipe, James Shepherd, Emma C. Thomson, The COVID- Genomics UK (COG-UK) Consortium§, David Bonsall, Christophe Fraser and Tanya Golubchik, 9 March 2021, Science.
DOI: 10.1126/science.abg0821
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