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

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

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.