Evaluating the Effects of SARS-CoV-2 Spike Mutation D614G on Transmissibility and Pathogenicity
Volz E, Hill V, McCrone JT, Price A, Jorgensen D, O'Toole Á, Southgate J, Johnson R, Jackson B, Nascimento FF, Rey SM, Nicholls SM, Colquhoun RM, da Silva Filipe A, Shepherd J, Pascall DJ, Shah R, Jesudason N, Li K, Jarrett R, Pacchiarini N, Bull M, Geidelberg L, Siveroni I, Koshy C, Wise E, Cortes N, Lynch J, Kidd S, Mori M, Fairley DJ, Curran T, McKenna JP, Adams H, Fraser C, Golubchik T, Bonsall D, Moore C, Caddy SL, Khokhar FA, Wantoch M, Reynolds N, Warne B, Maksimovic J, Spellman K, McCluggage K, John M, Beer R, Afifi S, Morgan S, Marchbank A, Kitchen C, Gulliver H, Merrick I, Guest M, Munn R, Workman T, Connor TR, Fuller W, Bresner C, Snell LB, Charalampous T, Nebbia G, Batra R, Edgeworth J, Robson SC, Beckett A, Loveson KF, Aanensen DM, Underwood AP, Yeats CA, Abudahab K, Taylor BEW, Menegazzo M, Clark G, Smith W, Khakh M, Fleming VM, Lister MM, Howson-Wells HC, Berry L, Boswell T, Joseph A, Willingham I, Bird P, Helmer T, Fallon K, Holmes C, Tang J, Raviprakash V, Campbell S, Sheriff N, Loose MW, Holmes N, Moore C, Carlile M, Wright V, Sang F, Debebe J, Coll F, Signell AW, Betancor G, Wilson HD, Feltwell T, Houldcroft CJ, Eldirdiri S, Kenyon A, Davis T, Pybus O, du Plessis L, Zarebski A, Raghwani J, Kraemer M, Francois S, Attwood S, Vasylyeva T, Torok ME, Hamilton WL, Goodfellow IG, Hall G, Jahun AS, Chaudhry Y, Hosmillo M, Pinckert ML, Georgana I, Yakovleva A, Meredith LW, Moses S, Lowe H, Ryan F, Fisher CL, Awan AR, Boyes J, Breuer J, Harris KA, Brown JR, Shah D, Atkinson L, Lee JCD, Alcolea-Medina A, Moore N, Cortes N, Williams R, Chapman MR, Levett LJ, Heaney J, Smith DL, Bashton M, Young GR, Allan J, Loh J, Randell PA, Cox A, Madona P, Holmes A, Bolt F, Price J, Mookerjee S, Rowan A, Taylor GP, Ragonnet-Cronin M, Johnson R, Boyd O, Volz EM, Brunker K, Smollett KL, Loman NJ, Quick J, McMurray C, Stockton J, Nicholls S, Rowe W, Poplawski R, Martinez-Nunez RT, Mason J, Robinson TI, O'Toole E, Watts J, Breen C, Cowell A, Ludden C, Sluga G, Machin NW, Ahmad SSY, George RP, Halstead F, Sivaprakasam V, Thomson EC, Shepherd JG, Asamaphan P, Niebel MO, Li KK, Shah RN, Jesudason NG, Parr YA, Tong L, Broos A, Mair D, Nichols J, Carmichael SN, Nomikou K, Aranday-Cortes E, Johnson N, Starinskij I, Robertson DL, Orton RJ, Hughes J, Vattipally S, Singer JB, Hale AD, Macfarlane-Smith LR, Harper KL, Taha Y, Payne BAI, Burton-Fanning S, Waugh S, Collins J, Eltringham G, Templeton KE, McHugh MP, Dewar R, Wastenge E, Dervisevic S, Stanley R, Prakash R, Stuart C, Elumogo N, Sethi DK, Meader EJ, Coupland LJ, Potter W, Graham C, Barton E, Padgett D, Scott G, Swindells E, Greenaway J, Nelson A, Yew WC, Resende Silva PC, Andersson M, Shaw R, Peto T, Justice A, Eyre D, Crooke D, Hoosdally S, Sloan TJ, Duckworth N, Walsh S, Chauhan AJ, Glaysher S, Bicknell K, Wyllie S, Butcher E, Elliott S, Lloyd A, Impey R, Levene N, Monaghan L, Bradley DT, Allara E, Pearson C, Muir P, Vipond IB, Hopes R, Pymont HM, Hutchings S, Curran MD, Parmar S, Lackenby A, Mbisa T, Platt S, Miah S, Bibby D, Manso C, Hubb J, Chand M, Dabrera G, Ramsay M, Bradshaw D, Thornton A, Myers R, Schaefer U, Groves N, Gallagher E, Lee D, Williams D, Ellaby N, Harrison I, Hartman H, Manesis N, Patel V, Bishop C, Chalker V, Osman H, Bosworth A, Robinson E, Holden MTG, Shaaban S, Birchley A, Adams A, Davies A, Gaskin A, Plimmer A, Gatica-Wilcox B, McKerr C, Moore C, Williams C, Heyburn D, De Lacy E, Hilvers E, Downing F, Shankar G, Jones H, Asad H, Coombes J, Watkins J, Evans JM, Fina L, Gifford L, Gilbert L, Graham L, Perry M, Morgan M, Cronin M, Craine N, Jones R, Howe R, Corden S, Rey S, Kumziene-Summerhayes S, Taylor S, Cottrell S, Jones S, Edwards S, O'Grady J, Page AJ, Wain J, Webber MA, Mather AE, Baker DJ, Rudder S, Yasir M, Thomson NM, Aydin A, Tedim AP, Kay GL, Trotter AJ, Gilroy RAJ, Alikhan N-F, de Oliveira Martins L, Le-Viet T, Meadows L, Kolyva A, Diaz M, Bell A, Gutierrez AV, Charles IG, Adriaenssens EM, Kingsley RA, Casey A, Simpson DA, Molnar Z, Thompson T, Acheson E, Masoli JAH, Knight BA, Hattersley A, Ellard S, Auckland C, Mahungu TW, Irish-Tavares D, Haque T, Bourgeois Y, Scarlett GP, Partridge DG, Raza M, Evans C, Johnson K, Liggett S, Baker P, Essex S, Lyons RA, Caller LG, Castellano S, Williams RJ, Kristiansen M, Roy S, Williams CA, Dyal PL, Tutill HJ, Panchbhaya YN, Forrest LM, Niola P, Findlay J, Brooks TT, Gavriil A, Mestek-Boukhibar L, Weeks S, Pandey S, Berry L, Jones K, Richter A, Beggs A, Smith CP, Bucca G, Hesketh AR, Harrison EM, Peacock SJ, Palmer S, Churcher CM, Bellis KL, Girgis ST, Naydenova P, Blane B, Sridhar S, Ruis C, Forrest S, Cormie C, Gill HK, Dias J, Higginson EE, Maes M, Young J, Kermack LM, Hadjirin NF, Aggarwal D, Griffith L, Swingler T, Davidson RK, Rambaut A, Williams T, Balcazar CE, Gallagher MD, O'Toole Á, Rooke S, Colquhoun R, Ashworth J, McCrone JT, Scher E, Yu X, Williamson KA, Stanton TD, Michell SL, Bewshea CM, Temperton B, Michelsen ML, Warwick-Dugdale J, Manley R, Farbos A, Harrison JW, Sambles CM, Studholme DJ, Jeffries AR, Darby AC, Hiscox JA, Paterson S, Iturriza-Gomara M, Jackson KA, Lucaci AO, Vamos EE, Hughes M, Rainbow L, Eccles R, Nelson C, Whitehead M, Turtle L, Haldenby ST, Gregory R, Gemmell M, Kwiatkowski D, de Silva TI, Smith N, Angyal A, Lindsey BB, Groves DC, Green LR, Wang D, Freeman TM, Parker MD, Keeley AJ, Parsons PJ, Tucker RM, Brown R, Wyles M, Constantinidou C, Unnikrishnan M, Ott S, Cheng JKJ, Bridgewater HE, Frost LR, Taylor-Joyce G, Stark R, Baxter L, Alam MT, Brown PE, McClure PC, Chappell JG, Tsoleridis T, Ball J, Gramatopoulos D, Buck D, Todd JA, Green A, Trebes A, MacIntyre-Cockett G, de Cesare M, Langford C, Alderton A, Amato R, Goncalves S, Jackson DK, Johnston I, Sillitoe J, Palmer S, Lawniczak M, Berriman M, Danesh J, Livett R, Shirley L, Farr B, Quail M, Thurston S, Park N, Betteridge E, Weldon D, Goodwin S, Nelson R, Beaver C, Letchford L, Jackson DA, Foulser L, McMinn L, Prestwood L, Kay S, Kane L, Dorman MJ, Martincorena I, Puethe C, Keatley J-P, Tonkin-Hill G, Smith C, Jamrozy D, Beale MA, Patel M, Ariani C, Spencer-Chapman M, Drury E, Lo S, Rajatileka S, Scott C, James K, Buddenborg SK, Berger DJ, Patel G, Garcia-Casado MV, Dibling T, McGuigan S, Rogers HA, Hunter AD, Souster E, Neaverson AS, Goodfellow I, Pybus OG & COG-UK Consortium(2021) Cell 184, 64-7.50E+12.
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. © 2020 The Author(s)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. © 2020 The Author(s)
