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

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Title: Evaluating the effects of SARS-CoV-2 Spike mutation D614G on transmissibility and pathogenicity
Authors: Volz, E
Hill, V
McCrone, J
Price, A
Jorgensen, D
O'Toole, A
Southgate, JA
Johnson, R
Jackson, B
Nascimento, F
Rey, S
Nicholls, S
Colquhoun, R
Da Silva Filipe, A
Shepherd, J
Pascall, D
Shah, R
Jesudason, N
Li, K
Jarrett, R
Pacchiarini, N
Bull, M
Geidelberg, L
Siveroni, I
Goodfellow, I
Loman, NJ
Pybus, O
Robertson, D
Thomson, E
Rambaut, A
Connor, T
The COVID-19 Genomics UK Consortium
Item Type: Journal Article
Abstract: In February 2020 a substitution at the interface between SARS-CoV-2 Spike protein subunits, Spike D614G, was observed in public databases. The Spike 614G variant subsequently increased in frequency in many locations throughout the world. Global patterns of dispersal of Spike 614G are suggestive of a selective advantage of this variant, however the origin of Spike 614G is associated with early colonization events in Europe and subsequent radiations to the rest of the world. Increasing frequency of 614G may therefore be due to a random founder effect. We investigate the hypothesis for positive selection of Spike 614G at the level of an individual country, the United Kingdom, using more than 25,000 whole genome SARS-CoV-2 sequences collected by COVID-19 Genomics UK Consortium. Using phylogenetic analysis, we identify Spike 614G and 614D clades with unique origins in the UK and from these we extrapolate and compare growth rates of co-circulating transmission clusters. We find that Spike 614G clusters are introduced in the UK later on average than 614D clusters and grow to larger size after adjusting for time of introduction. Phylodynamic analysis does not show a significant increase in growth rates for clusters with the 614G variant, but population genetic modelling indicates that 614G increases in frequency relative to 614D in a manner consistent with a selective advantage. We also investigate the potential influence of Spike 614D versus G on virulence by matching a subset of records to clinical data on patient outcomes. We do not find any indication that patients infected with the Spike 614G variant have higher COVID-19 mortality, but younger patients have slightly increased odds of 614G carriage. Despite the availability of a very large data set, well represented by both Spike 614 variants, not all approaches showed a conclusive signal of higher transmission rate for 614G, but significant differences in growth, size, and composition of these lineages indicate a need for continued study.
Issue Date: 7-Jan-2021
Date of Acceptance: 11-Nov-2020
URI: http://hdl.handle.net/10044/1/84079
DOI: 10.1016/j.cell.2020.11.020
ISSN: 0092-8674
Publisher: Elsevier
Start Page: 64
End Page: 75.e11
Journal / Book Title: Cell
Volume: 184
Issue: 1
Copyright Statement: © 2020 The Author(s). Published by Elsevier Inc. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
Sponsor/Funder: Medical Research Council (MRC)
Medical Research Council (MRC)
Funder's Grant Number: MR/R015600/1
Keywords: COVID-19
founder effect
Amino Acid Substitution
Aspartic Acid
Genome, Viral
Spike Glycoprotein, Coronavirus
United Kingdom
Whole Genome Sequencing
COG-UK Consortium
Aspartic Acid
Amino Acid Substitution
Genome, Viral
Spike Glycoprotein, Coronavirus
United Kingdom
Whole Genome Sequencing
The COVID-19 Genomics UK Consortium
06 Biological Sciences
11 Medical and Health Sciences
Developmental Biology
Publication Status: Published
Online Publication Date: 2020-11-19
Appears in Collections:Department of Metabolism, Digestion and Reproduction
Faculty of Medicine
Imperial College London COVID-19
School of Public Health

This item is licensed under a Creative Commons License Creative Commons