SARS-CoV-2 within-host diversity and transmission

Oxford Virus Sequencing Analysis Group (OVSG), The COVID-19 Genomics UK (COG-UK) Consortium, 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 GreenSamuel 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, Thomas R. Connor, Shirin Ashraf, Ana da Silva Filipe, James Shepherd, Emma C. Thomson, David Bonsall, Christophe Fraser, Tanya Golubchik, Matthew Bashton, Andrew Nelson, Darren Smith, Greg Young

*Corresponding author for this work

    Research output: Contribution to journalArticlepeer-review

    275 Citations (Scopus)
    87 Downloads (Pure)

    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.

    Original languageEnglish
    Article numbereabg0821
    Number of pages12
    JournalScience
    Volume372
    Issue number6539
    Early online date9 Mar 2021
    DOIs
    Publication statusPublished - 16 Apr 2021

    Keywords

    • COVID-19/immunology
    • Coinfection/virology
    • Coronavirus Infections/virology
    • Coronavirus OC43, Human
    • Family Characteristics
    • Genetic Variation
    • Genome, Viral
    • Humans
    • Immune Evasion
    • Mutation
    • Phylogeny
    • RNA, Viral/genetics
    • RNA-Seq
    • SARS-CoV-2/genetics
    • Selection, Genetic
    • Spike Glycoprotein, Coronavirus/genetics
    • United Kingdom
    • Viral Load

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