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

Volz, ErikORCID logo; Hill, VerityORCID logo; McCrone, John T; Price, AnnaORCID logo; Jorgensen, DavidORCID logo; O’Toole, ÁineORCID logo; Southgate, Joel; Johnson, Robert; Jackson, Ben; Nascimento, Fabricia F; +21 more...Rey, Sara M; Nicholls, Samuel MORCID logo; Colquhoun, Rachel M; da Silva Filipe, Ana; Shepherd, James; Pascall, David J; Shah, Rajiv; Jesudason, Natasha; Li, Kathy; Jarrett, Ruth; Pacchiarini, Nicole; Bull, Matthew; Geidelberg, Lily; Siveroni, Igor; Goodfellow, Ian; Loman, Nicholas J; Pybus, Oliver G; Robertson, David L; Thomson, Emma CORCID logo; Rambaut, Andrew; and Connor, Thomas RORCID logo (2020) Evaluating the effects of SARS-CoV-2 Spike mutation D614G on transmissibility and pathogenicity. BMJ. DOI: 10.1101/2020.07.31.20166082
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Summary

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 data set, 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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