Evaluating the effects of SARS-CoV-2 spike mutation D614G on transmissibility and pathogenicity

COG-UK Consortium; 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; Ian Goodfellow; Nicholas J Loman; Oliver G Pybus; David L Robertson; Emma C Thomson; Andrew Rambaut; Thomas R Connor

doi:10.1016/j.cell.2020.11.020

Evaluating the effects of SARS-CoV-2 spike mutation D614G on transmissibility and pathogenicity

COG-UK Consortium, 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 LiRuth Jarrett, Nicole Pacchiarini, Matthew Bull, Lily Geidelberg, Igor Siveroni, Ian Goodfellow, Nicholas J Loman, Oliver G Pybus, David L Robertson, Emma C Thomson, Andrew Rambaut, Thomas R Connor

Biosciences

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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
Number of pages	24
Journal	Cell
Volume	184
Issue number	1
Early online date	19 Nov 2020
DOIs	https://doi.org/10.1016/j.cell.2020.11.020
Publication status	Published - 7 Jan 2021

Keywords

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

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10.1016/j.cell.2020.11.020Licence: Creative Commons: Attribution (CC BY)

Volz2021Final published version, 3.74 MBLicence: Creative Commons: Attribution (CC BY)

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COG-UK Consortium, 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., ... Connor, T. R. (2021). Evaluating the effects of SARS-CoV-2 spike mutation D614G on transmissibility and pathogenicity. Cell, 184(1), 64-75.e11. Advance online publication. https://doi.org/10.1016/j.cell.2020.11.020

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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.",

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COG-UK Consortium, 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, Goodfellow, I, Loman, NJ, Pybus, OG, Robertson, DL, Thomson, EC, Rambaut, A & Connor, TR 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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AU - Volz, Erik

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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 - Goodfellow, Ian

AU - Loman, Nicholas J

AU - Pybus, Oliver G

AU - Robertson, David L

AU - Thomson, Emma C

AU - Rambaut, Andrew

AU - Connor, Thomas R

PY - 2021/1/7

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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.

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KW - epidemiology

KW - evolution

KW - founder effect

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DO - 10.1016/j.cell.2020.11.020

M3 - Article

C2 - 33275900

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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