The United Kingdom has led the global effort on sequencing the SARS-CoV-2 genome. In doing so, they have been able to inform the world about emerging variants and unpack key aspects of viral transmission. Two important determinants of variant spread are how frequently they arise within individuals, and how likely they are to be transmitted.

Now, an analysis of SARS-CoV-2 genome diversity in more than 1,000 people in the U.K. suggests that if viral mutations do arise, they can be transmitted in some cases but they rarely persist in subsequent transmissions. Most variants, the authors noted, are either lost, or occasionally fixed, at the point of transmission, with minimal persistence of shared diversity. “Our observations indicate the within-host emergence of vaccine- and therapeutic-escape mutations is likely to be relatively rare,” said the authors, “at least during early infection when viral loads are high.” They suggest that transmission-enhancing and/or immune-escape variants are likely to arise infrequently, but could spread rapidly if successfully transmitted.

This work is published in Science in the paper, “SARS-CoV-2 within-host diversity and transmission.” The research was posted to bioRxiv on December 10, 2020.

Most analyses of mutations in SARS-CoV-2 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.

To better characterize diversity in single human hosts, Katrina Lythgoe, PhD, research group leader at Big Data Institute, Nuffield department of medicine, University of Oxford, and her 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 U.K. 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. In addition, 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.

And, 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.

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