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A phylogeny-based metric for estimating changes in transmissibility from recurrent mutations in SARS-CoV-2

View ORCID ProfileDamien Richard, View ORCID ProfileLiam P Shaw, View ORCID ProfileRob Lanfear, View ORCID ProfileMislav Acman, View ORCID ProfileChristopher J Owen, View ORCID ProfileCedric CS Tan, View ORCID ProfileLucy van Dorp, View ORCID ProfileFrançois Balloux
doi: https://doi.org/10.1101/2021.05.06.442903
Damien Richard
1UCL Genetics Institute, University College London, London WC1E 6BT, UK
2Division of Infection and Immunity, University College London, London, WC1E 6BT, UK
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Liam P Shaw
3Department of Zoology, University of Oxford, Oxford OX1 3DZ, UK
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Rob Lanfear
4Department of Ecology and Evolution, Research School of Biology, Australian National University, Canberra, ACT, Australia
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Mislav Acman
1UCL Genetics Institute, University College London, London WC1E 6BT, UK
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Christopher J Owen
1UCL Genetics Institute, University College London, London WC1E 6BT, UK
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Cedric CS Tan
1UCL Genetics Institute, University College London, London WC1E 6BT, UK
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Lucy van Dorp
1UCL Genetics Institute, University College London, London WC1E 6BT, UK
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François Balloux
1UCL Genetics Institute, University College London, London WC1E 6BT, UK
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  • For correspondence: f.balloux@ucl.ac.uk
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Abstract

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged in late 2019 and spread globally to cause the COVID-19 pandemic. Despite the constant accumulation of genetic variation in the SARS-CoV-2 population, there was little evidence for the emergence of significantly more transmissible lineages in the first half of 2020. Around November 2020, several more contagious and possibly more virulent ‘Variants of Concern’ (VoCs) were detected near-simultaneously in various regions of the world. These VoCs share some mutations and deletions that haven arisen recurrently in distinct genetic backgrounds. Here, we build on our previous work modelling the association of mutations to SARS-CoV-2 transmissibility and characterise the contribution of individual recurrent mutations and deletions to estimated viral transmissibility. We estimate enhanced transmissibility associated to mutations characteristic of VoCs and identify a tendency for cytidine to thymidine (C→T) substitutions to be associated to a reduction in estimated transmissibility. We then assess how patterns of estimated transmissibility in all SARS-CoV-2 clades have varied over the course of the COVID-19 pandemic by summing transmissibility estimates for all individual mutations carried by any sequenced genome analysed. Such an approach recovers 501Y.v1 (B.1.1.7) as the most transmissible clade currently in circulation. By assessing transmissibility over the time of sampling, we observe a tendency for estimated transmissibility within clades to slightly decrease in most clades. Although subtle, this pattern is consistent with the expectation of a decay in transmissibility in mainly non-recombining lineages caused by the accumulation of weakly deleterious mutations. SARS-CoV-2 remains a highly transmissible pathogen, though such a trend could conceivably play a role in the turnover of different global viral clades observed over the pandemic so far.

Caveats

  • This work is not about the severity of disease. We do not analyse the severity of disease. We do not present any evidence that SARS-CoV-2 has decreased in severity.

  • Lineage replacement dynamics are affected by many factors. The trend we recover for a decrease in inferred transmissibility of a clade over time is a small effect. We caution against over-interpretation. This result would not affect the management of the SARS-CoV-2 pandemic: for example, we make no claims about any impact on the efficacy of particular non-pharmaceutical interventions (NPIs).

  • Our phylogeny-based method to infer changes in estimated transmissibility due to recurrent mutations and deletions makes a number of simplifying assumptions. These may not all be valid. The consistent trend for the slight decrease we report might be due to an as-yet-unidentified systematic bias.

Competing Interest Statement

The authors have declared no competing interest.

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 4.0 International license.
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Posted May 07, 2021.
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A phylogeny-based metric for estimating changes in transmissibility from recurrent mutations in SARS-CoV-2
Damien Richard, Liam P Shaw, Rob Lanfear, Mislav Acman, Christopher J Owen, Cedric CS Tan, Lucy van Dorp, François Balloux
bioRxiv 2021.05.06.442903; doi: https://doi.org/10.1101/2021.05.06.442903
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A phylogeny-based metric for estimating changes in transmissibility from recurrent mutations in SARS-CoV-2
Damien Richard, Liam P Shaw, Rob Lanfear, Mislav Acman, Christopher J Owen, Cedric CS Tan, Lucy van Dorp, François Balloux
bioRxiv 2021.05.06.442903; doi: https://doi.org/10.1101/2021.05.06.442903

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