Evaluating the Effects of SARS-CoV-2 Spike Mutation D614G on Transmissibility and Pathogenicity
Erik Volz(Imperial College London), Verity Hill(University of Edinburgh), John T. McCrone(University of Edinburgh), Anna Price(Cardiff University), David Jorgensen(Imperial College London), Áine O’Toole(University of Edinburgh), Joel Southgate(Cardiff and Vale University Health Board), Robert Johnson(Imperial College London), Ben Jackson(University of Edinburgh), Fabrícia F. Nascimento(Imperial College London), Sara Rey(Public Health Wales), Samuel M. Nicholls(University of Birmingham), Rachel Colquhoun(University of Edinburgh), Ana da Silva Filipe(MRC University of Glasgow Centre for Virus Research), James G. Shepherd(MRC University of Glasgow Centre for Virus Research), David J. Pascall(Glasgow Centre for Population Health), Rajiv Shah(MRC University of Glasgow Centre for Virus Research), Natasha Jesudason(MRC University of Glasgow Centre for Virus Research), Kathy Li(MRC University of Glasgow Centre for Virus Research), Ruth F. Jarrett(MRC University of Glasgow Centre for Virus Research), Nicole Pacchiarini(Public Health Wales), Matthew Bull(Public Health Wales), Lily Geidelberg(Imperial College London), Igor Siveroni(Imperial College London), Cherian Koshy(University of Cambridge), Emma L. Wise(University of Birmingham), Nick Cortes(Royal Veterinary College), Jessica Lynch(MRC University of Glasgow Centre for Virus Research), Stephen P. Kidd(MRC University of Glasgow Centre for Virus Research), Matilde Mori(University of Edinburgh), Derek Fairley(Quadram Institute), Tanya Curran, James McKenna(MRC University of Glasgow Centre for Virus Research), Helen Adams, Christophe Fraser, Tanya Golubchik, David Bonsall, Catrin E. Moore, Sarah Caddy, Fahad Khokhar, Michelle Wantoch, Nicola Reynolds, Ben Warne, Joshua Maksimovic(MRC University of Glasgow Centre for Virus Research), Karla Spellman, Kathryn McCluggage, John P.T. Mo, Robert Beer, Safiah Afifi, Siân Morgan(University of Edinburgh), Angela Marchbank, Anna Price(Cardiff University), Christine Kitchen, Huw Gulliver(Imperial College London), Ian Merrick(MRC University of Glasgow Centre for Virus Research), Joel Southgate(Cardiff and Vale University Health Board), Martyn F. Guest, Robert J. Munn, Trudy Workman(Cardiff University), Thomas R. Connor(Cardiff University), William Fuller, Catherine Bresner(University of Cambridge), Luke B. Snell(Public Health Wales), Themoula Charalampous, Gaia Nebbia(MRC University of Glasgow Centre for Virus Research), Rahul Batra, Jonathan Edgeworth(Quadram Institute), 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(Quadram Institute), Nadine Holmes, Christopher Moore, Matthew Carlile, Victoria Wright, Fei Sang, Johnny Debebe, Francesc Coll, Adrian W. Signell, Gilberto Betancor, Harry Wilson(Public Health Wales), Theresa Feltwell, Charlotte J. Houldcroft, Sahar Eldirdiri, Anita Kenyon, Thomas Davis, Oliver G. Pybus(Royal Veterinary College), Louis du Plessis, Alex E. Zarebski, Jayna Raghwani, Moritz U. G. Kraemer, Sarah François, Stephen W. Attwood(Quadram Institute), Tetyana I. Vasylyeva(Royal Veterinary College), M. Estée Török, William L. Hamilton, Ian Goodfellow(University of Cambridge), Grant Hall, Aminu S. Jahun, Yasmin Chaudhry, Myra Hosmillo, Malte L. Pinckert, Iliana Georgana, Anna Yakovleva(University of Cambridge), Luke W. Meredith, Samuel Moses, Hannah Lowe, Felicity Ryan, Chloe L. Fisher, Ali Raza Awan, John Boyes(Cardiff University), Judith Breuer, Kathryn Harris(University of Birmingham), Julianne R. Brown, Divya Shah, Laura Atkinson, Jack C. D. Lee, Adela Alcolea-Medina(Imperial College London), Nathan Moore, Nicholas Cortes, Rebecca Williams, Michael Chapman(MRC University of Glasgow Centre for Virus Research), Lisa J. Levett, Judith Heaney, Darren Smith, Matthew Bashton, Gregory R. Young(University of Birmingham), John N. Allan, Joshua P. Loh, Paul Randell, Alison D. Cox, Pinglawathee Madona, Alison Holmes(Public Health Wales), Frances Bolt, James Price(Imperial College London), Siddharth Mookerjee, Aileen Rowan, Graham P. Taylor, Manon Ragonnet‐Cronin, Fabricia F. Nascimento(Imperial College London), David Jorgensen(Imperial College London), Igor Siveroni(Imperial College London), Rob Johnson(Imperial College London), Olivia Boyd, Lily Geidelberg(Imperial College London), Erik Volz(Imperial College London), Kirstyn Brunker(Imperial College London), Katherine Smollett(Imperial College London), Nicholas J. Loman(Imperial College London), Joshua Quick(Imperial College London), Claire McMurray, Joanne Stockton(Imperial College London), Sam Nicholls(Imperial College London), Will Rowe, Radoslaw Poplawski, Rocío T. Martínez-Nuñez(University of Birmingham), Jenifer Mason, Trevor I. Robinson, Elaine O’Toole, Joanne Watts(University of Birmingham), Cassie Breen, Angela Cowell, Catherine Ludden, Graciela Sluga, Nicholas W. Machin, Shazaad S.Y. Ahmad(University of Edinburgh), Ryan P. George, Fenella Halstead, Venkat Sivaprakasam, Emma C. Thomson(MRC University of Glasgow Centre for Virus Research), James G. Shepherd(MRC University of Glasgow Centre for Virus Research), Patawee Asamaphan, Marc Niebel, Kathy Li(MRC University of Glasgow Centre for Virus Research), Rajiv Shah(MRC University of Glasgow Centre for Virus Research), Natasha Jesudason(MRC University of Glasgow Centre for Virus Research), Yasmin A. Parr(MRC University of Glasgow Centre for Virus Research), L. Tong(MRC University of Glasgow Centre for Virus Research), Alice Broos, Daniel Mair, Jenna Nichols(Royal Veterinary College), Stephen Carmichael(MRC University of Glasgow Centre for Virus Research), Kyriaki Nomikou(MRC University of Glasgow Centre for Virus Research), Elihú Aranday-Cortés, Natasha Johnson(Imperial College London), Igor Starinskij, Ana da Silva Filipe(MRC University of Glasgow Centre for Virus Research), David L. Robertson(MRC University of Glasgow Centre for Virus Research), Richard Orton, Joseph Hughes, Vattipally B. Sreenu, Joshua B. Singer(Imperial College London), Antony Hale(Imperial College London), Louissa Macfarlane-Smith(MRC University of Glasgow Centre for Virus Research), Katherine L. Harper(MRC University of Glasgow Centre for Virus Research), Yusri Taha, Brendan Payne, Shirelle Burton-Fanning, Sheila Waugh, Jennifer Collins, Gary Eltringham, Kate Templeton, M. McHugh, Rebecca Dewar, Elizabeth Wastenge, Samir Dervisevic, Rachael Stanley, Reenesh Prakash, Claire Stuart, Ngozi Elumogo, Dheeraj Sethi, Emma Meader, Lindsay Coupland, Will Potter, Clive Graham, Edward Barton, Debra Padgett, Garren Scott, Emma Swindells, Jane Greenaway, Andrew Nelson, Wen C. Yew, Paola C. Resende Silva, Monique Andersson, R. H. Shaw, Tim Peto(MRC University of Glasgow Centre for Virus Research), Anita Justice, David W. Eyre(University of Edinburgh), Derrick Crooke, Sarah Hoosdally, Tim J. Sloan, Nichola Duckworth(MRC University of Glasgow Centre for Virus Research), Sarah Walsh, Anoop Chauhan, Sharon Glaysher(MRC University of Glasgow Centre for Virus Research), Kelly Bicknell, Sarah Wyllie, Ethan Butcher, Scott Elliott(University of Birmingham), Allyson Lloyd, Robert Impey, Nick Levene, Lynn Monaghan, Declan Bradley, Elias Allara, Clare Pearson, Peter Muir, Ian B. Vipond(MRC University of Glasgow Centre for Virus Research), Richard Hopes, Hannah M. Pymont, Stephanie Hutchings, Martin D. Curran, Surendra Parmar, Angie Lackenby, Tamyo Mbisa, Steven G. Platt, Shahjahan Miah, David Bibby, Carmen de Guerrero Manso, Jonathan Hubb, Meera Chand, Gavin Dabrera, Mary Ramsay, Daniel Bradshaw, Alicia Thornton(MRC University of Glasgow Centre for Virus Research), Richard Myers, Ulf Schaefer, Natalie Groves, Eileen Gallagher, David Lee, David A. Williams, Nicholas Ellaby, Ian Harrison, Hassan Hartman, Nikos Manesis, Vineet Patel, Chloe Bishop(MRC University of Glasgow Centre for Virus Research), Vicki Chalker(MRC University of Glasgow Centre for Virus Research), Husam Osman(University of Birmingham), Andrew Bosworth(University of Cambridge), Esther Robinson, Matthew T. G. Holden, Sharif Shaaban, Alec Birchley, Alexander Adams, Alisha Davies, Amy Gaskin(University of Edinburgh), Amy Plimmer, Bree Gatica-Wilcox, Caoimhe McKerr, Catherine Moore, Chris Williams, David Heyburn, Elen De Lacy, Ember Hilvers, Fatima Downing, Giri Shankar, Hannah Jones, Hibo Asad, Jason D. Coombes(MRC University of Glasgow Centre for Virus Research), Joanne Watkins, Johnathan M. Evans, Laia Fina, Laura Gifford, Lauren Gilbert, Lee Graham, Malorie Perry, Mari Morgan, Matthew Bull(Public Health Wales), Michelle Cronin, Nicole Pacchiarini(Public Health Wales), Noel Craine, Rachel Jones, Robin Howe, Sally Corden, Sara Rey(Public Health Wales), Sara Kumziene-Summerhayes, Sarah Taylor(Public Health Wales), Simon Cottrell, Sophie Jones(University of Edinburgh), Sue Edwards, Justin O’Grady, Andrew J. Page(Public Health Wales), John Wain(Public Health Wales), Mark Webber, Alison E. Mather, David Baker, Steven Rudder, Muhammad Yasir, Nicholas M. Thomson, Alp Aydin(Imperial College London), Ana P. Tedim, Gemma L. Kay, Alexander J. Trotter(Glasgow Centre for Population Health), Rachel Gilroy, Nabil-Fareed Alikhan, Leonardo de Oliveira Martins(MRC University of Glasgow Centre for Virus Research), Thanh Le-Viet, Lizzie Meadows, Anastasia Kolyva, María Díaz, Andrew Bell, Ana Victoria Gutiérrez, Ian G. Charles, Evelien M. Adriaenssens, Robert A. Kingsley, Anna Casey, David Simpson, Zoltán Molnár(University of Edinburgh), Thomas Thompson, Erwan Acheson(University of Cambridge), Jane Masoli, Bridget Knight(MRC University of Glasgow Centre for Virus Research), Andrew T. Hattersley(Cardiff University), Sian Ellard(MRC University of Glasgow Centre for Virus Research), Cressida Auckland, Tabitha Mahungu(Quadram Institute), Dianne Irish-Tavares, Tanzina Haque, Yann Bourgeois, Garry P. Scarlett(University of Edinburgh), David G. Partridge, Mohammad Raza, Cariad Evans, KATE JOHNSON, Steven Liggett, Paul Baker, Sarah Essex, Ronan A Lyons, Laura Caller, Sergi Castellano, Rachel Williams(Imperial College London), Mark Kristiansen, Sunando Roy, Charlotte A. Williams, Patricia Dyal, Helena J. Tutill, Yasmin Panchbhaya, Leysa Forrest, Paola Niola, Jacqueline Findlay, T Brooks, Artemis Gavriil, Lamia Mestek, Sam Weeks, Sarojini Pandey, Lisa Berry, Katie Jones, Alex Richter, Andrew D. Beggs, Colin P. Smith, Giselda Bucca(University of Birmingham), Andrew R. Hesketh, Ewan M. Harrison, Sharon J. Peacock, Sophie Palmer, Carol Churcher(University of Edinburgh), Katherine L. Bellis, Sophia T. Girgis, Plamena Naydenova(University of Edinburgh), Beth Blane, Sushmita Sridhar, Chris Ruis, Sally Forrest, Claire Cormie, Harmeet K. Gill, Joana Dias, Ellen E. Higginson, Mailis Maes, Jamie Young, Leanne M. Kermack, Nazreen F. Hadjirin, Dinesh Aggarwal, Luke Griffith, T.E. Swingler, Rose K. Davidson, Andrew Rambaut(Institut de Biologia Evolutiva), Thomas Williams, Carlos E. Balcazar, Michael D. Gallagher, Áine O’Toole(University of Edinburgh), Stefan Rooke, Ben Jackson(University of Edinburgh), Rachel Colquhoun(University of Edinburgh), Jordan Ashworth(Quadram Institute), Verity Hill(University of Edinburgh), John T. McCrone(University of Edinburgh), Emily Scher(University of Edinburgh), Xiaoyu Yu, Kathleen A. Williamson(University of Edinburgh), Thomas D. Stanton(University of Edinburgh), Stephen L. Michell, Claire Bewshea(University of Edinburgh), Ben Temperton(University of Edinburgh), Michelle L. Michelsen, Joanna Warwick-Dugdale, Robin Manley, Audrey Farbos, Jamie Harrison, Christine Sambles, David J. Studholme(University of Edinburgh), Aaron R. Jeffries, Alistair C. Darby, Julian A. Hiscox, Steve Paterson, Miren Iturriza-Gomara, Kathryn Jackson, Anita O. Lucaci(Glasgow Centre for Population Health), Edith E. Vamos, Margaret Hughes, Lucille Rainbow, Richard Eccles, Charlotte Nelson, Mark Whitehead(University of Edinburgh), Lance Turtle, Sam Haldenby, Richard I. Gregory, Matthew Gemmell, Dominic Kwiatkowski, Thushan I. de Silva, Darren Smith, Adrienn Angyal, Benjamin B. Lindsey, Danielle C. Groves, Luke R. Green(Public Health Wales), Dennis Wang, Timothy M. Freeman, Matthew D. Parker, Alexander J. Keeley, Paul J. Parsons, Rachel Tucker, Rebecca Brown, Matthew Wyles, Chrystala Constantinidou, Meera Unnikrishnan, Sascha Ott, Jeffrey K. J. Cheng, Hannah E. Bridgewater(University of Edinburgh), Lucy R. Frost, Grace Taylor-Joyce(Public Health Wales), Richard Stark, Laura Baxter, Mohammad Tauqeer Alam, Paul E. Brown, C. Patrick McClure, Joseph Chappell, Theocharis Tsoleridis, Jonathan K. Ball, Dimitris Grammatopoulos, David Buck, John A. Todd, Angie Green, Amy Trebes, George MacIntyre-Cockett, Mariateresa de Cesare, Cordelia Langford, Alex Alderton(MRC University of Glasgow Centre for Virus Research), Roberto Amato(Imperial College London), Sónia Gonçalves, David K. Jackson, Ian Johnston, John Sillitoe, Steve Palmer, Mara Lawniczak, Matthew Berriman, John Danesh, Rich Livett(University of Edinburgh), Lesley Shirley(University of Cambridge), Ben W. Farr(Imperial College London), Mike Quail, Scott Thurston, Naomi Park(Public Health Wales), Emma Betteridge(Imperial College London), Danni Weldon, Scott Goodwin, Rachel Nelson(University of Edinburgh), Charlotte Beaver, Laura Letchford, David A. Jackson, Luke Foulser(MRC University of Glasgow Centre for Virus Research), Liz McMinn, Liam Prestwood, Sally Kay(University of Edinburgh), Leanne Kane, Matthew J. Dorman, Inigo Martincorena(University of Edinburgh), Christoph Puethe, Jon-Paul Keatley, Gerry Tonkin‐Hill, Christen Smith, Dorota Jamrozy, Mathew A. Beale, Minal Patel, Cristina V. Ariani, Michael Spencer-Chapman, Eleanor Drury, Stephanie W. Lo, Shavanthi Rajatileka, Carol Scott, Keith James, Sarah K. Buddenborg, Duncan Berger, Gaurang Patel, Maria V. Garcia-Casado(University of Birmingham), Thomas Dibling, Samantha McGuigan, Hazel Rogers(MRC University of Glasgow Centre for Virus Research), Adam D. Hunter, Emily Souster, Alexandra Neaverson, Ian Goodfellow(University of Cambridge), Nicholas J. Loman(Quadram Institute), Oliver G. Pybus(Royal Veterinary College), David L. Robertson(MRC University of Glasgow Centre for Virus Research), Emma C. Thomson(MRC University of Glasgow Centre for Virus Research), Andrew Rambaut(Institut de Biologia Evolutiva), Thomas R. Connor(Cardiff University)
Cited by 1,082Open Access
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.
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