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

Erik Volz ORCID logo ; Verity Hill ORCID logo ; John T McCrone ; Anna Price ORCID logo ; David Jorgensen ORCID logo ; Áine O’Toole ORCID logo ; Joel Southgate ; Robert Johnson ; Ben Jackson ; Fabricia F Nascimento ; +21 more... Sara M Rey ; Samuel M Nicholls ORCID logo ; 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 ORCID logo ; Andrew Rambaut ; Thomas R Connor ORCID 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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