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 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; 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

doi:10.1126/SCIENCE.ABG0821

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

Applied Sciences Department

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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.

Original language	English
Article number	eabg0821
Number of pages	12
Journal	Science
Volume	372
Issue number	6539
Early online date	9 Mar 2021
DOIs	https://doi.org/10.1126/SCIENCE.ABG0821
Publication status	Published - 16 Apr 2021

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Oxford Virus Sequencing Analysis Group (OVSG), The COVID-19 Genomics UK (COG-UK) Consortium, Lythgoe, K. A., Hall, M., Ferretti, L., de Cesare, M., MacIntyre-Cockett, G., Trebes, A., Andersson, M., Otecko, N., Wise, E. L., Moore, N., Lynch, J., Kidd, S., Cortes, N., Mori, M., Williams, R., Vernet, G., Justice, A., ... Young, G. (2021). SARS-CoV-2 within-host diversity and transmission. Science, 372(6539), Article eabg0821. https://doi.org/10.1126/SCIENCE.ABG0821

@article{5726e2c8c92e45e2892ff1b00da351b6,

title = "SARS-CoV-2 within-host diversity and transmission",

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.",

author = "{Oxford Virus Sequencing Analysis Group (OVSG)} and {The COVID-19 Genomics UK (COG-UK) Consortium} and Lythgoe, {Katrina A.} and Matthew Hall and Luca Ferretti and {de Cesare}, Mariateresa and George MacIntyre-Cockett and Amy Trebes and Monique Andersson and Newton Otecko and Wise, {Emma L.} and Nathan Moore and Jessica Lynch and Stephen Kidd and Nicholas Cortes and Matilde Mori and Rebecca Williams and Gabrielle Vernet and Anita Justice and Angie Green and Nicholls, {Samuel M.} and Ansari, {M. Azim} and Lucie Abeler-D{\"o}rner and Moore, {Catrin E.} and Peto, {Timothy E.A.} and Eyre, {David W.} and Robert Shaw and Peter Simmonds and David Buck and Todd, {John A.} and Connor, {Thomas R.} and Shirin Ashraf and {da Silva Filipe}, Ana and James Shepherd and Thomson, {Emma C.} and David Bonsall and Christophe Fraser and Tanya Golubchik and Matthew Bashton and Andrew Nelson and Darren Smith and Greg Young",

note = "Funding information: We gratefully acknowledge the UK COVID-19 Genomics Consortium (COG UK) for funding. COG-UK is supported by funding from the Medical Research Council (MRC) part of UK Research & Innovation (UKRI), the National Institute of Health Research (NIHR), and Genome Research Limited, operating as the Wellcome Sanger Institute. The research was also supported by a Wellcome Core Award (203141/Z/16/Z) with additional funding from the NIHR Oxford Biomedical Research Centre. The views expressed are those of the authors and not necessarily those of the NHS, the NIHR, or the Department of Health. K.A.L. and M.A.A. were supported by The Wellcome Trust and The Royal Society (107652/Z/15/Z to K.A.L. and 220171/Z/20/Z to M.A.A.). M.H., L.F., M.d.C., G.M.C., N.O., L.A.D., D.B., C.F., and T.G. were supported by Li Ka Shing Foundation funding awarded to C.F. P.S. was supported by a Wellcome Investigator Award (WT103767MA). J.A.T. was supported by a Wellcome Core Award (203141/Z/16/Z). C.E.M. was supported by the Fleming Fund at the Department of Health and Social Care, UK; the Wellcome Trust (209142/Z/17/Z) and the Bill and Melinda Gates Foundation (OPP1176062). DWE is a Robertson Fellow and an NIHR Oxford BRC Senior Fellow. Matthew Bashton, Andrew Nelson, Darren Smith, Greg Young are members of the COVID-19 Genomics UK (COG-UK) consortium.",

year = "2021",

month = apr,

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doi = "10.1126/SCIENCE.ABG0821",

language = "English",

volume = "372",

journal = "Science",

issn = "0036-8075",

publisher = "American Association for the Advancement of Science",

number = "6539",

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Oxford Virus Sequencing Analysis Group (OVSG), The COVID-19 Genomics UK (COG-UK) Consortium, Lythgoe, KA, Hall, M, Ferretti, L, de Cesare, M, MacIntyre-Cockett, G, Trebes, A, Andersson, M, Otecko, N, Wise, EL, Moore, N, Lynch, J, Kidd, S, Cortes, N, Mori, M, Williams, R, Vernet, G, Justice, A, Green, A, Nicholls, SM, Ansari, MA, Abeler-Dörner, L, Moore, CE, Peto, TEA, Eyre, DW, Shaw, R, Simmonds, P, Buck, D, Todd, JA, Connor, TR, Ashraf, S, da Silva Filipe, A, Shepherd, J, Thomson, EC, Bonsall, D, Fraser, C, Golubchik, T, Bashton, M , Nelson, A , Smith, D & Young, G 2021, 'SARS-CoV-2 within-host diversity and transmission', Science, vol. 372, no. 6539, eabg0821. https://doi.org/10.1126/SCIENCE.ABG0821

TY - JOUR

T1 - SARS-CoV-2 within-host diversity and transmission

AU - Oxford Virus Sequencing Analysis Group (OVSG)

AU - The COVID-19 Genomics UK (COG-UK) Consortium

AU - Lythgoe, Katrina A.

AU - Hall, Matthew

AU - Ferretti, Luca

AU - de Cesare, Mariateresa

AU - MacIntyre-Cockett, George

AU - Trebes, Amy

AU - Andersson, Monique

AU - Otecko, Newton

AU - Wise, Emma L.

AU - Moore, Nathan

AU - Lynch, Jessica

AU - Kidd, Stephen

AU - Cortes, Nicholas

AU - Mori, Matilde

AU - Williams, Rebecca

AU - Vernet, Gabrielle

AU - Justice, Anita

AU - Green, Angie

AU - Nicholls, Samuel M.

AU - Ansari, M. Azim

AU - Abeler-Dörner, Lucie

AU - Moore, Catrin E.

AU - Peto, Timothy E.A.

AU - Eyre, David W.

AU - Shaw, Robert

AU - Simmonds, Peter

AU - Buck, David

AU - Todd, John A.

AU - Connor, Thomas R.

AU - Ashraf, Shirin

AU - da Silva Filipe, Ana

AU - Shepherd, James

AU - Thomson, Emma C.

AU - Bonsall, David

AU - Fraser, Christophe

AU - Golubchik, Tanya

AU - Bashton, Matthew

AU - Nelson, Andrew

AU - Smith, Darren

AU - Young, Greg

N1 - Funding information: We gratefully acknowledge the UK COVID-19 Genomics Consortium (COG UK) for funding. COG-UK is supported by funding from the Medical Research Council (MRC) part of UK Research & Innovation (UKRI), the National Institute of Health Research (NIHR), and Genome Research Limited, operating as the Wellcome Sanger Institute. The research was also supported by a Wellcome Core Award (203141/Z/16/Z) with additional funding from the NIHR Oxford Biomedical Research Centre. The views expressed are those of the authors and not necessarily those of the NHS, the NIHR, or the Department of Health. K.A.L. and M.A.A. were supported by The Wellcome Trust and The Royal Society (107652/Z/15/Z to K.A.L. and 220171/Z/20/Z to M.A.A.). M.H., L.F., M.d.C., G.M.C., N.O., L.A.D., D.B., C.F., and T.G. were supported by Li Ka Shing Foundation funding awarded to C.F. P.S. was supported by a Wellcome Investigator Award (WT103767MA). J.A.T. was supported by a Wellcome Core Award (203141/Z/16/Z). C.E.M. was supported by the Fleming Fund at the Department of Health and Social Care, UK; the Wellcome Trust (209142/Z/17/Z) and the Bill and Melinda Gates Foundation (OPP1176062). DWE is a Robertson Fellow and an NIHR Oxford BRC Senior Fellow. Matthew Bashton, Andrew Nelson, Darren Smith, Greg Young are members of the COVID-19 Genomics UK (COG-UK) consortium.

PY - 2021/4/16

Y1 - 2021/4/16

N2 - 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.

AB - 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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U2 - 10.1126/SCIENCE.ABG0821

DO - 10.1126/SCIENCE.ABG0821

M3 - Article

C2 - 33688063

AN - SCOPUS:85104899848

SN - 0036-8075

VL - 372

JO - Science

JF - Science

IS - 6539

M1 - eabg0821

ER -

SARS-CoV-2 within-host diversity and transmission

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