Evaluating the Effects of SARS-CoV-2 Spike Mutation D614G on Transmissibility and Pathogenicity
Erik Volz, Verity Hill, John T. McCrone, Anna Price, David Jorgensen, Áine O’Toole, Joel Southgate, Robert Johnson, Ben Jackson, Fabrícia F. Nascimento, Sara Rey, Samuel M. Nicholls, Rachel Colquhoun, Ana da Silva Filipe, James G. Shepherd, David J. Pascall, Rajiv Shah, Natasha Jesudason, Kathy Li, Ruth F. Jarrett, Nicole Pacchiarini, Matthew Bull, Lily Geidelberg, Igor Siveroni, Cherian Koshy, Emma L. Wise, Nick Cortes, Jessica Lynch, Stephen P. Kidd, Matilde Mori, Derek Fairley, Tanya Curran, James McKenna, Helen Adams, Christophe Fraser, Tanya Golubchik, David Bonsall, Catrin E. Moore, Sarah Caddy, Fahad Khokhar, Michelle Wantoch, Nicola Reynolds, Ben Warne, Joshua Maksimovic, Karla Spellman, Kathryn McCluggage, John P.T. Mo, Robert Beer, Safiah Afifi, Siân Morgan, Angela Marchbank, Anna Price, Christine Kitchen, Huw Gulliver, Ian Merrick, Joel Southgate, Martyn F. Guest, Robert J. Munn, Trudy Workman, Thomas R. Connor, William Fuller, Catherine Bresner, Luke B. Snell, Themoula Charalampous, Gaia Nebbia, Rahul Batra, Jonathan Edgeworth, Samuel C. Robson, Angela H. Beckett, Katie F. Loveson, David M. Aanensen, Anthony P. Underwood, Corin Yeats, Khalil Abudahab, Ben Taylor, Mirko Menegazzo, Gemma Clark, Darren Smith, Manjinder Khakh, Vicki M. Fleming, Michelle M. Lister, Hannah C. Howson‐Wells, Louise Berry, Tim Boswell, Amelia Joseph, Iona Willingham, Paul Bird, Thomas Helmer, Karlie Fallon, Christopher W. Holmes, Julian W. Tang, Veena Raviprakash, Sharon Campbell, Nicola Sheriff, Matthew Loose, Nadine Holmes, Christopher Moore, Matthew Carlile, Victoria Wright, Fei Sang
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.