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

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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 languageEnglish
Pages (from-to)64-75.e11
Number of pages24
JournalCell
Volume184
Issue number1
Early online date19 Nov 2020
DOIs
Publication statusPublished - 7 Jan 2021

Keywords

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

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