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Shepherd, James; Koshy, Cherian; Wise, Emma; Curran, Tanya; Adams, Helen; Moore, Catrin; Khokhar, Fahad A.; Reynolds, Nicola; Afifi, Safiah; Price, Anna; Kitchen, Christine; Merrick, Ian; Connor, Thomas R.; Bresner, Catherine; Robson, Samuel C.; Menegazzo, Mirko; Clark, Gemma; Fleming, Vicki M.; Howson-Wells, Hannah C.; Bird, Paul; Helmer, Thomas; Fallon, Karlie; du Plessis, Louis; Attwood, Stephen; Vasylyeva, Tetyana; Chaudhry, Yasmin; Moses, Samuel; Ryan, Felicity; Brown, Julianne Rose; Lee, Jack C.D.; Alcolea-Medina, Adela; Moore, Nathan; Cortes, Nicholas; Williams, Rebecca; Smith, Darren L.; Holmes, Alison; Price, James; Rowan, Aileen; Taylor, Graham P.; Watts, Joanne; Ludden, Catherine; George, Ryan P.; Li, Kathy K.; Carmichael, Stephen N.; Johnson, Natasha; Orton, Richard J.; Hale, Antony D.; Harper, Katherine L.; Eltringham, Gary; Coupland, Lindsay J.; Barton, Edward; Scott, Garren; Yew, Wen C.; Resende Silva, Paola C.; Justice, Anita; Chand, Meera; Williams, David; Harrison, Ian; Chalker, Vicki; Heyburn, David; Downing, Fatima; Watkins, Joanne; Howe, Robin; Taylor, Sarah; Wain, John; Rudder, Steven; Gilroy, Rachel A.J.; Alikhan, Nabil-Fareed; Casey, Anna; Liggett, Steven; Caller, Laura G.; Panchbhaya, Yasmin N.; Forrest, Leysa M.; Findlay, Jacqueline; Beggs, Andrew; Hesketh, Andrew R.; Higginson, Ellen E.; Aggarwal, Dinesh; Colquhoun, Rachel; Ashworth, Jordan; McCrone, J.T.; Michell, Stephen L.; Hughes, Margaret; Rainbow, Lucille; Haldenby, Sam T.; Green, Luke R.; Parker, Matthew D.; Bridgewater, Hannah E.; Alam, Mohammad T.; Quail, Mike; Thurston, Scott; Beaver, Charlotte; McMinn, Liz; Puethe, Christoph; Tonkin-Hill, Gerry; Smith, Christen; Jamrozy, Dorota; Patel, Minal; Drury, Eleanor; Loman, Nicholas J.
Cell, 01/2021, Volume: 184, Issue: 1Journal Article
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. Display omitted •Increasing frequency of SARS-CoV-2 D614G is consistent with a selective advantage•Phylodynamic analyses do not show significantly different growth of D614G clusters•There is no association of D614G replacement with greater severity of infection•The D614G replacement is associated with higher viral loads and younger patient age Analysis of the spread and frequency of SARS-CoV-2 D614G in the United Kingdom suggests a selective advantage for this strain that is associated with higher viral loads in younger patients but not higher COVID-19 clinical severity or mortality.
