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Shared SARS-CoV-2 diversity suggests localised transmission of minority variants

View ORCID ProfileKatrina A. Lythgoe, View ORCID ProfileMatthew 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, Anita Justice, Angie Green, M. Azim Ansari, Lucie Abeler-Dörner, Catrin E. Moore, Tim E. A. Peto, Robert Shaw, Peter Simmonds, David Buck, John A. Todd, on behalf of OVSG Analysis Group, David Bonsall, Christophe Fraser, View ORCID ProfileTanya Golubchik
doi: https://doi.org/10.1101/2020.05.28.118992
Katrina A. Lythgoe
1Big Data Institute, Nuffield Department of Medicine, University of Oxford, Old Road Campus, Oxford OX3 7FL, UK
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  • ORCID record for Katrina A. Lythgoe
  • For correspondence: Tanya.Golubchik@bdi.ox.ac.uk Katrina.Lythgoe@bdi.ox.ac.uk Matthew.Hall@bdi.ox.ac.uk
Matthew Hall
1Big Data Institute, Nuffield Department of Medicine, University of Oxford, Old Road Campus, Oxford OX3 7FL, UK
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  • ORCID record for Matthew Hall
  • For correspondence: Tanya.Golubchik@bdi.ox.ac.uk Katrina.Lythgoe@bdi.ox.ac.uk Matthew.Hall@bdi.ox.ac.uk
Luca Ferretti
1Big Data Institute, Nuffield Department of Medicine, University of Oxford, Old Road Campus, Oxford OX3 7FL, UK
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Mariateresa de Cesare
1Big Data Institute, Nuffield Department of Medicine, University of Oxford, Old Road Campus, Oxford OX3 7FL, UK
2Wellcome Centre for Human Genetics, Nuffield Department of Medicine, NIHR Biomedical Research Centre, University of Oxford, Old Road Campus, Oxford OX3 7BN, UK
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George MacIntyre-Cockett
1Big Data Institute, Nuffield Department of Medicine, University of Oxford, Old Road Campus, Oxford OX3 7FL, UK
2Wellcome Centre for Human Genetics, Nuffield Department of Medicine, NIHR Biomedical Research Centre, University of Oxford, Old Road Campus, Oxford OX3 7BN, UK
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Amy Trebes
2Wellcome Centre for Human Genetics, Nuffield Department of Medicine, NIHR Biomedical Research Centre, University of Oxford, Old Road Campus, Oxford OX3 7BN, UK
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Monique Andersson
3Oxford University Hospitals NHS Foundation Trust, John Radcliffe Hospital, Headington, Oxford, OX3 9DU, UK
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Newton Otecko
1Big Data Institute, Nuffield Department of Medicine, University of Oxford, Old Road Campus, Oxford OX3 7FL, UK
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Emma L. Wise
4Hampshire Hospitals NHS Foundation Trust, Basingstoke and North Hampshire Hospital, Basingstoke, RG24 9NA, UK
6School of Biosciences and Medicine, University of Surrey, Guildford, GU2 7XH, UK
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Nathan Moore
4Hampshire Hospitals NHS Foundation Trust, Basingstoke and North Hampshire Hospital, Basingstoke, RG24 9NA, UK
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Jessica Lynch
4Hampshire Hospitals NHS Foundation Trust, Basingstoke and North Hampshire Hospital, Basingstoke, RG24 9NA, UK
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Stephen Kidd
4Hampshire Hospitals NHS Foundation Trust, Basingstoke and North Hampshire Hospital, Basingstoke, RG24 9NA, UK
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Nicholas Cortes
4Hampshire Hospitals NHS Foundation Trust, Basingstoke and North Hampshire Hospital, Basingstoke, RG24 9NA, UK
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Matilde Mori
7School of Medicine, University of Southampton, Southampton, SO17 1BJ, UK
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Anita Justice
3Oxford University Hospitals NHS Foundation Trust, John Radcliffe Hospital, Headington, Oxford, OX3 9DU, UK
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Angie Green
2Wellcome Centre for Human Genetics, Nuffield Department of Medicine, NIHR Biomedical Research Centre, University of Oxford, Old Road Campus, Oxford OX3 7BN, UK
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M. Azim Ansari
5Peter Medawar Building for Pathogen Research, University of Oxford, OX1 3SY, UK
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Lucie Abeler-Dörner
1Big Data Institute, Nuffield Department of Medicine, University of Oxford, Old Road Campus, Oxford OX3 7FL, UK
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Catrin E. Moore
1Big Data Institute, Nuffield Department of Medicine, University of Oxford, Old Road Campus, Oxford OX3 7FL, UK
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Tim E. A. Peto
3Oxford University Hospitals NHS Foundation Trust, John Radcliffe Hospital, Headington, Oxford, OX3 9DU, UK
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Robert Shaw
3Oxford University Hospitals NHS Foundation Trust, John Radcliffe Hospital, Headington, Oxford, OX3 9DU, UK
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Peter Simmonds
5Peter Medawar Building for Pathogen Research, University of Oxford, OX1 3SY, UK
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David Buck
2Wellcome Centre for Human Genetics, Nuffield Department of Medicine, NIHR Biomedical Research Centre, University of Oxford, Old Road Campus, Oxford OX3 7BN, UK
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John A. Todd
2Wellcome Centre for Human Genetics, Nuffield Department of Medicine, NIHR Biomedical Research Centre, University of Oxford, Old Road Campus, Oxford OX3 7BN, UK
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David Bonsall
1Big Data Institute, Nuffield Department of Medicine, University of Oxford, Old Road Campus, Oxford OX3 7FL, UK
2Wellcome Centre for Human Genetics, Nuffield Department of Medicine, NIHR Biomedical Research Centre, University of Oxford, Old Road Campus, Oxford OX3 7BN, UK
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Christophe Fraser
1Big Data Institute, Nuffield Department of Medicine, University of Oxford, Old Road Campus, Oxford OX3 7FL, UK
2Wellcome Centre for Human Genetics, Nuffield Department of Medicine, NIHR Biomedical Research Centre, University of Oxford, Old Road Campus, Oxford OX3 7BN, UK
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Tanya Golubchik
1Big Data Institute, Nuffield Department of Medicine, University of Oxford, Old Road Campus, Oxford OX3 7FL, UK
2Wellcome Centre for Human Genetics, Nuffield Department of Medicine, NIHR Biomedical Research Centre, University of Oxford, Old Road Campus, Oxford OX3 7BN, UK
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  • ORCID record for Tanya Golubchik
  • For correspondence: Tanya.Golubchik@bdi.ox.ac.uk Katrina.Lythgoe@bdi.ox.ac.uk Matthew.Hall@bdi.ox.ac.uk
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Summary

SARS-CoV-2, the causative agent of COVID-19, emerged in late 2019 causing a global pandemic, with the United Kingdom (UK) one of the hardest hit countries. Rapid sequencing and publication of consensus genomes have enabled phylogenetic analysis of the virus, demonstrating SARS-CoV-2 evolves relatively slowly1, but with multiple sites in the genome that appear inconsistent with the overall consensus phylogeny2. To understand these discrepancies, we used veSEQ3, a targeted RNA-seq approach, to quantify minor allele frequencies in 413 clinical samples from two UK locations. We show that SARS-CoV-2 infections are characterised by extensive within-host diversity, which is frequently shared among infected individuals with patterns consistent with geographical structure. These results were reproducible in data from other sequencing locations around the UK, where we find evidence of mixed infection by major circulating lineages with patterns that cannot readily be explained by artefacts in the data. We conclude that SARS-CoV-2 diversity is transmissible, and propose that geographic patterns are generated by co-circulation of distinct viral populations. Co-transmission of mixed populations could open opportunities for resolving clusters of transmission and understanding pathogenesis.

Competing Interest Statement

The authors have declared no competing interest.

Footnotes

  • The OVSG Analysis Group membership comprises John A Todd, Tanya Golubchik, David Bonsall, Christophe Fraser, Derrick Crook, Tim Peto, Monique Andersson, Katie Jeffries, David Eyre, Timothy Walker, Robert Shaw, Peter Simmonds, Katrina Lythgoe, Luca Ferretti, Matthew Hall, Mariateresa de Cesare, Paolo Piazza, Richard Cornall.

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license.
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Shared SARS-CoV-2 diversity suggests localised transmission of minority variants
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, Anita Justice, Angie Green, M. Azim Ansari, Lucie Abeler-Dörner, Catrin E. Moore, Tim E. A. Peto, Robert Shaw, Peter Simmonds, David Buck, John A. Todd, on behalf of OVSG Analysis Group, David Bonsall, Christophe Fraser, Tanya Golubchik
bioRxiv 2020.05.28.118992; doi: https://doi.org/10.1101/2020.05.28.118992
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Shared SARS-CoV-2 diversity suggests localised transmission of minority variants
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, Anita Justice, Angie Green, M. Azim Ansari, Lucie Abeler-Dörner, Catrin E. Moore, Tim E. A. Peto, Robert Shaw, Peter Simmonds, David Buck, John A. Todd, on behalf of OVSG Analysis Group, David Bonsall, Christophe Fraser, Tanya Golubchik
bioRxiv 2020.05.28.118992; doi: https://doi.org/10.1101/2020.05.28.118992

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