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

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

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669 Citations (Scopus)


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
Issue number1
Early online date18 Nov 2020
Publication statusPublished - 7 Jan 2021


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

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