SARS-CoV-2 within-host diversity and transmission

Katrina Lythgoe(University of Oxford), Matthew Hall(University of Oxford), Luca Ferretti(University of Oxford), Mariateresa de Cesare(Centre for Human Genetics), George MacIntyre-Cockett(Centre for Human Genetics), Amy Trebes(Centre for Human Genetics), Monique Andersson(Stellenbosch University), Newton O. Otecko(University of Oxford), Emma L. Wise(University of Surrey), Nathan Moore(Hampshire Hospitals NHS Foundation Trust), Jessica Lynch(Hampshire Hospitals NHS Foundation Trust), Stephen P. Kidd(Hampshire Hospitals NHS Foundation Trust), Nicholas Cortes(Hampshire Hospitals NHS Foundation Trust), Matilde Mori(University of Southampton), Rebecca Williams(Hampshire Hospitals NHS Foundation Trust), Gabrielle Vernet(Hampshire Hospitals NHS Foundation Trust), Anita Justice(John Radcliffe Hospital), Angie Green(Centre for Human Genetics), Samuel M. Nicholls(University of Birmingham), M. Azim Ansari(University of Oxford), Lucie Abeler‐Dörner(University of Oxford), Catrin E. Moore(University of Oxford), Tim Peto(John Radcliffe Hospital), David W. Eyre(John Radcliffe Hospital), R. H. Shaw(John Radcliffe Hospital), Peter Simmonds(University of Oxford), David Buck(Centre for Human Genetics), John A. Todd(Centre for Human Genetics), on behalf of the Oxford Virus Sequencing Analysis Group (OVSG)(Public Health Wales), Thomas R. Connor(Public Health Wales), Shirin Ashraf(MRC University of Glasgow Centre for Virus Research), Ana da Silva Filipe(MRC University of Glasgow Centre for Virus Research), James G. Shepherd(MRC University of Glasgow Centre for Virus Research), Emma C. Thomson(Centre for Human Genetics), David Bonsall(Centre for Human Genetics), Christophe Fraser(Centre for Human Genetics), Tanya Golubchik(University of Oxford)
Science
March 9, 2021
Cited by 431Open Access
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Abstract

Extensive global sampling and sequencing of the pandemic virus severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have enabled researchers to monitor its spread and to identify concerning new variants. Two important determinants of variant spread are how frequently they arise within individuals and how likely they are to be transmitted. To characterize within-host diversity and transmission, we deep-sequenced 1313 clinical samples from the United Kingdom. SARS-CoV-2 infections are characterized by low levels of within-host diversity when viral loads are high and by a narrow bottleneck at transmission. Most variants are either lost or occasionally fixed at the point of transmission, with minimal persistence of shared diversity, patterns that are readily observable on the phylogenetic tree. Our results suggest that transmission-enhancing and/or immune-escape SARS-CoV-2 variants are likely to arise infrequently but could spread rapidly if successfully transmitted.


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