Evaluating the Effects of SARS-CoV-2 Spike Mutation D614G on Transmissibility and Pathogenicity

Erik Volz; Verity Hill; John T. McCrone; Anna Price; David Jorgensen; Áine O'Toole; Joel Southgate; Robert Johnson; Ben Jackson; Fabricia F. Nascimento; Sara M. Rey; Samuel M. Nicholls; Rachel M. Colquhoun; Ana da Silva Filipe; James Shepherd; David J. Pascall; Rajiv Shah; Natasha Jesudason; Kathy Li; Ruth Jarrett; Nicole Pacchiarini; Matthew Bull; Lily Geidelberg; Igor Siveroni; Cherian Koshy; Emma Wise; Nick Cortes; Jessica Lynch; Stephen Kidd; Matilde Mori; Derek J. Fairley; Tanya Curran; James P. McKenna; Helen Adams; Christophe Fraser; Tanya Golubchik; David Bonsall; Catrin Moore; Sarah L. Caddy; Fahad A. Khokhar; Michelle Wantoch; Nicola Reynolds; Ben Warne; Joshua Maksimovic; Karla Spellman; Kathryn McCluggage; Michaela John; Robert Beer; Sally Forrest; Jonathan Ball

doi:10.1016/j.cell.2020.11.020

Evaluating the Effects of SARS-CoV-2 Spike Mutation D614G on Transmissibility and Pathogenicity

Erik Volz, Verity Hill, John T. McCrone, Anna Price, David Jorgensen, Áine O'Toole, Joel Southgate, Robert Johnson, Ben Jackson, Fabricia F. Nascimento, Sara M. Rey, Samuel M. Nicholls, Rachel M. Colquhoun, Ana da Silva Filipe, James Shepherd, David J. Pascall, Rajiv Shah, Natasha Jesudason, Kathy Li, Ruth JarrettNicole Pacchiarini, Matthew Bull, Lily Geidelberg, Igor Siveroni, Cherian Koshy, Emma Wise, Nick Cortes, Jessica Lynch, Stephen Kidd, Matilde Mori, Derek J. Fairley, Tanya Curran, James P. McKenna, Helen Adams, Christophe Fraser, Tanya Golubchik, David Bonsall, Catrin Moore, Sarah L. Caddy, Fahad A. Khokhar, Michelle Wantoch, Nicola Reynolds, Ben Warne, Joshua Maksimovic, Karla Spellman, Kathryn McCluggage, Michaela John, Robert Beer, Sally Forrest, Jonathan Ball

Liverpool School of Tropical Medicine

Research output: Contribution to journal › Article › peer-review

731 Citations (Scopus)

Abstract

Global dispersal and increasing frequency of the SARS-CoV-2 spike protein variant D614G are suggestive of a selective advantage but may also be due to a random founder effect. We investigate the hypothesis for positive selection of spike D614G in the United Kingdom using more than 25,000 whole genome SARS-CoV-2 sequences. Despite the availability of a large dataset, well represented by both spike 614 variants, not all approaches showed a conclusive signal of positive selection. Population genetic analysis indicates that 614G increases in frequency relative to 614D in a manner consistent with a selective advantage. We do not find any indication that patients infected with the spike 614G variant have higher COVID-19 mortality or clinical severity, but 614G is associated with higher viral load and younger age of patients. Significant differences in growth and size of 614G phylogenetic clusters indicate a need for continued study of this variant.

Original language	English
Pages (from-to)	64-75.e11
Journal	Cell
Volume	184
Issue number	1
DOIs	https://doi.org/10.1016/j.cell.2020.11.020
Publication status	Published - 7 Jan 2021

Keywords

COVID-19
epidemiology
evolution
founder effect
SARS-CoV-2
spike

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10.1016/j.cell.2020.11.020Licence: CC BY

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Volz, E., Hill, V., McCrone, J. T., Price, A., Jorgensen, D., O'Toole, Á., Southgate, J., Johnson, R., Jackson, B., Nascimento, F. F., Rey, S. M., Nicholls, S. M., Colquhoun, R. M., da Silva Filipe, A., Shepherd, J., Pascall, D. J., Shah, R., Jesudason, N., Li, K., ... Ball, J. (2021). Evaluating the Effects of SARS-CoV-2 Spike Mutation D614G on Transmissibility and Pathogenicity. Cell, 184(1), 64-75.e11. https://doi.org/10.1016/j.cell.2020.11.020

@article{e868ccaf27c34a04971f522ac440bb66,

title = "Evaluating the Effects of SARS-CoV-2 Spike Mutation D614G on Transmissibility and Pathogenicity",

abstract = "Global dispersal and increasing frequency of the SARS-CoV-2 spike protein variant D614G are suggestive of a selective advantage but may also be due to a random founder effect. We investigate the hypothesis for positive selection of spike D614G in the United Kingdom using more than 25,000 whole genome SARS-CoV-2 sequences. Despite the availability of a large dataset, well represented by both spike 614 variants, not all approaches showed a conclusive signal of positive selection. Population genetic analysis indicates that 614G increases in frequency relative to 614D in a manner consistent with a selective advantage. We do not find any indication that patients infected with the spike 614G variant have higher COVID-19 mortality or clinical severity, but 614G is associated with higher viral load and younger age of patients. Significant differences in growth and size of 614G phylogenetic clusters indicate a need for continued study of this variant.",

keywords = "COVID-19, epidemiology, evolution, founder effect, SARS-CoV-2, spike",

author = "Erik Volz and Verity Hill and McCrone, \{John T.\} and Anna Price and David Jorgensen and {\'A}ine O'Toole and Joel Southgate and Robert Johnson and Ben Jackson and Nascimento, \{Fabricia F.\} and Rey, \{Sara M.\} and Nicholls, \{Samuel M.\} and Colquhoun, \{Rachel M.\} and \{da Silva Filipe\}, Ana and James Shepherd and Pascall, \{David J.\} and Rajiv Shah and Natasha Jesudason and Kathy Li and Ruth Jarrett and Nicole Pacchiarini and Matthew Bull and Lily Geidelberg and Igor Siveroni and Cherian Koshy and Emma Wise and Nick Cortes and Jessica Lynch and Stephen Kidd and Matilde Mori and Fairley, \{Derek J.\} and Tanya Curran and McKenna, \{James P.\} and Helen Adams and Christophe Fraser and Tanya Golubchik and David Bonsall and Catrin Moore and Caddy, \{Sarah L.\} and Khokhar, \{Fahad A.\} and Michelle Wantoch and Nicola Reynolds and Ben Warne and Joshua Maksimovic and Karla Spellman and Kathryn McCluggage and Michaela John and Robert Beer and Sally Forrest and Jonathan Ball",

year = "2021",

month = jan,

day = "7",

doi = "10.1016/j.cell.2020.11.020",

language = "English",

volume = "184",

pages = "64--75.e11",

journal = "Cell",

issn = "0092-8674",

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number = "1",

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Volz, E, Hill, V, McCrone, JT, Price, A, Jorgensen, D, O'Toole, Á, Southgate, J, Johnson, R, Jackson, B, Nascimento, FF, Rey, SM, Nicholls, SM, Colquhoun, RM, da Silva Filipe, A, Shepherd, J, Pascall, DJ, Shah, R, Jesudason, N, Li, K, Jarrett, R, Pacchiarini, N, Bull, M, Geidelberg, L, Siveroni, I, Koshy, C, Wise, E, Cortes, N, Lynch, J, Kidd, S, Mori, M, Fairley, DJ, Curran, T, McKenna, JP, Adams, H, Fraser, C, Golubchik, T, Bonsall, D, Moore, C, Caddy, SL, Khokhar, FA, Wantoch, M, Reynolds, N, Warne, B, Maksimovic, J, Spellman, K, McCluggage, K, John, M, Beer, R, Forrest, S & Ball, J 2021, 'Evaluating the Effects of SARS-CoV-2 Spike Mutation D614G on Transmissibility and Pathogenicity', Cell, vol. 184, no. 1, pp. 64-75.e11. https://doi.org/10.1016/j.cell.2020.11.020

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T1 - Evaluating the Effects of SARS-CoV-2 Spike Mutation D614G on Transmissibility and Pathogenicity

AU - Volz, Erik

AU - Hill, Verity

AU - McCrone, John T.

AU - Price, Anna

AU - Jorgensen, David

AU - O'Toole, Áine

AU - Southgate, Joel

AU - Johnson, Robert

AU - Jackson, Ben

AU - Nascimento, Fabricia F.

AU - Rey, Sara M.

AU - Nicholls, Samuel M.

AU - Colquhoun, Rachel M.

AU - da Silva Filipe, Ana

AU - Shepherd, James

AU - Pascall, David J.

AU - Shah, Rajiv

AU - Jesudason, Natasha

AU - Li, Kathy

AU - Jarrett, Ruth

AU - Pacchiarini, Nicole

AU - Bull, Matthew

AU - Geidelberg, Lily

AU - Siveroni, Igor

AU - Koshy, Cherian

AU - Wise, Emma

AU - Cortes, Nick

AU - Lynch, Jessica

AU - Kidd, Stephen

AU - Mori, Matilde

AU - Fairley, Derek J.

AU - Curran, Tanya

AU - McKenna, James P.

AU - Adams, Helen

AU - Fraser, Christophe

AU - Golubchik, Tanya

AU - Bonsall, David

AU - Moore, Catrin

AU - Caddy, Sarah L.

AU - Khokhar, Fahad A.

AU - Wantoch, Michelle

AU - Reynolds, Nicola

AU - Warne, Ben

AU - Maksimovic, Joshua

AU - Spellman, Karla

AU - McCluggage, Kathryn

AU - John, Michaela

AU - Beer, Robert

AU - Forrest, Sally

AU - Ball, Jonathan

PY - 2021/1/7

Y1 - 2021/1/7

N2 - Global dispersal and increasing frequency of the SARS-CoV-2 spike protein variant D614G are suggestive of a selective advantage but may also be due to a random founder effect. We investigate the hypothesis for positive selection of spike D614G in the United Kingdom using more than 25,000 whole genome SARS-CoV-2 sequences. Despite the availability of a large dataset, well represented by both spike 614 variants, not all approaches showed a conclusive signal of positive selection. Population genetic analysis indicates that 614G increases in frequency relative to 614D in a manner consistent with a selective advantage. We do not find any indication that patients infected with the spike 614G variant have higher COVID-19 mortality or clinical severity, but 614G is associated with higher viral load and younger age of patients. Significant differences in growth and size of 614G phylogenetic clusters indicate a need for continued study of this variant.

AB - Global dispersal and increasing frequency of the SARS-CoV-2 spike protein variant D614G are suggestive of a selective advantage but may also be due to a random founder effect. We investigate the hypothesis for positive selection of spike D614G in the United Kingdom using more than 25,000 whole genome SARS-CoV-2 sequences. Despite the availability of a large dataset, well represented by both spike 614 variants, not all approaches showed a conclusive signal of positive selection. Population genetic analysis indicates that 614G increases in frequency relative to 614D in a manner consistent with a selective advantage. We do not find any indication that patients infected with the spike 614G variant have higher COVID-19 mortality or clinical severity, but 614G is associated with higher viral load and younger age of patients. Significant differences in growth and size of 614G phylogenetic clusters indicate a need for continued study of this variant.

KW - COVID-19

KW - epidemiology

KW - evolution

KW - founder effect

KW - SARS-CoV-2

KW - spike

U2 - 10.1016/j.cell.2020.11.020

DO - 10.1016/j.cell.2020.11.020

M3 - Article

SN - 0092-8674

VL - 184

SP - 64-75.e11

JO - Cell

JF - Cell

IS - 1

ER -

Evaluating the Effects of SARS-CoV-2 Spike Mutation D614G on Transmissibility and Pathogenicity

Abstract

Keywords

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