Evaluating the Effects of SARS-CoV-2 Spike Mutation D614G on Transmissibility and Pathogenicity

Authors: 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, Johnny Debebe, Francesc Coll, Adrian W. Signell, Gilberto Betancor, Harry Wilson, Theresa Feltwell, Charlotte J. Houldcroft, Sahar Eldirdiri, Anita Kenyon, Thomas Davis, Oliver G. Pybus, Louis du Plessis, Alex E. Zarebski, Jayna Raghwani, Moritz U. G. Kraemer, Sarah François, Stephen W. Attwood, Tetyana I. Vasylyeva, M. Estée Török, William L. Hamilton, Ian Goodfellow, Grant Hall, Aminu S. Jahun, Yasmin Chaudhry, Myra Hosmillo, Malte L. Pinckert, Iliana Georgana, Anna Yakovleva, Luke W. Meredith, Samuel Moses, Hannah Lowe, Felicity Ryan, Chloe L. Fisher, Ali Raza Awan, John Boyes, Judith Breuer, Kathryn Harris, Julianne R. Brown, Divya Shah, Laura Atkinson, Jack C. D. Lee, Adela Alcolea-Medina, Nathan Moore, Nicholas Cortes, Rebecca Williams, Michael Chapman, Lisa J. Levett, Judith Heaney, Darren Smith, Matthew Bashton, Gregory R. Young, John N. Allan, Joshua P. Loh, Paul Randell, Alison D. Cox, Pinglawathee Madona, Alison Holmes, Frances Bolt, James Price, Siddharth Mookerjee, Aileen Rowan, Graham P. Taylor, Manon Ragonnet‐Cronin, Fabricia F. Nascimento, David Jorgensen, Igor Siveroni, Rob Johnson, Olivia Boyd, Lily Geidelberg, Erik Volz, Kirstyn Brunker, Katherine Smollett, Nicholas J. Loman, Joshua Quick, Claire McMurray, Joanne Stockton, Sam Nicholls, Will Rowe, Radoslaw Poplawski, Rocío T. Martínez-Nuñez, Jenifer Mason, Trevor I. Robinson, Elaine O’Toole, Joanne Watts, Cassie Breen, Angela Cowell, Catherine Ludden, Graciela Sluga, Nicholas W. Machin, Shazaad S.Y. Ahmad, Ryan P. George, Fenella Halstead, Venkat Sivaprakasam, Emma C. Thomson, James G. Shepherd, Patawee Asamaphan, Marc Niebel, Kathy Li, Rajiv Shah, Natasha Jesudason, Yasmin A. Parr, L. Tong, Alice Broos, Daniel Mair, Jenna Nichols, Stephen Carmichael, Kyriaki Nomikou, Elihú Aranday-Cortés, Natasha Johnson, Igor Starinskij, Ana da Silva Filipe, David L. Robertson, Richard Orton, Joseph Hughes, Vattipally B. Sreenu, Joshua B. Singer, Antony Hale, Louissa Macfarlane-Smith, Katherine L. Harper, 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, Anita Justice, David W. Eyre, Derrick Crooke, Sarah Hoosdally, Tim J. Sloan, Nichola Duckworth, Sarah Walsh, Anoop Chauhan, Sharon Glaysher, Kelly Bicknell, Sarah Wyllie, Ethan Butcher, Scott Elliott, Allyson Lloyd, Robert Impey, Nick Levene, Lynn Monaghan, Declan Bradley, Elias Allara, Clare Pearson, Peter Muir, Ian B. Vipond, 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, 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, Vicki Chalker, Husam Osman, Andrew Bosworth, Esther Robinson, Matthew T. G. Holden, Sharif Shaaban, Alec Birchley, Alexander Adams, Alisha Davies, Amy Gaskin, 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, Joanne Watkins, Johnathan M. Evans, Laia Fina, Laura Gifford, Lauren Gilbert, Lee Graham, Malorie Perry, Mari Morgan, Matthew Bull, Michelle Cronin, Nicole Pacchiarini, Noel Craine, Rachel Jones, Robin Howe, Sally Corden, Sara Rey, Sara Kumziene-Summerhayes, Sarah Taylor, Simon Cottrell, Sophie Jones, Sue Edwards, Justin O’Grady, Andrew J. Page, John Wain, Mark Webber, Alison E. Mather, David Baker, Steven Rudder, Muhammad Yasir, Nicholas M. Thomson, Alp Aydin, Ana P. Tedim, Gemma L. Kay, Alexander J. Trotter, Rachel Gilroy, Nabil-Fareed Alikhan, Leonardo de Oliveira Martins, 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, Thomas Thompson, Erwan Acheson, Jane Masoli, Bridget Knight, Andrew T. Hattersley, Sian Ellard, Cressida Auckland, Tabitha Mahungu, Dianne Irish-Tavares, Tanzina Haque, Yann Bourgeois, Garry P. Scarlett, David G. Partridge, Mohammad Raza, Cariad Evans, KATE JOHNSON, Steven Liggett, Paul Baker, Sarah Essex, Ronan A Lyons, Laura Caller, Sergi Castellano, Rachel Williams, 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, Andrew R. Hesketh, Ewan M. Harrison, Sharon J. Peacock, Sophie Palmer, Carol Churcher, Katherine L. Bellis, Sophia T. Girgis, Plamena Naydenova, 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, Thomas Williams, Carlos E. Balcazar, Michael D. Gallagher, Áine O’Toole, Stefan Rooke, Ben Jackson, Rachel Colquhoun, Jordan Ashworth, Verity Hill, John T. McCrone, Emily Scher, Xiaoyu Yu, Kathleen A. Williamson, Thomas D. Stanton, Stephen L. Michell, Claire Bewshea, Ben Temperton, Michelle L. Michelsen, Joanna Warwick-Dugdale, Robin Manley, Audrey Farbos, Jamie Harrison, Christine Sambles, David J. Studholme, Aaron R. Jeffries, Alistair C. Darby, Julian A. Hiscox, Steve Paterson, Miren Iturriza-Gomara, Kathryn Jackson, Anita O. Lucaci, Edith E. Vamos, Margaret Hughes, Lucille Rainbow, Richard Eccles, Charlotte Nelson, Mark Whitehead, 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, 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, Lucy R. Frost, Grace Taylor-Joyce, 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, Roberto Amato, Sónia Gonçalves, David K. Jackson, Ian Johnston, John Sillitoe, Steve Palmer, Mara Lawniczak, Matthew Berriman, John Danesh, Rich Livett, Lesley Shirley, Ben W. Farr, Mike Quail, Scott Thurston, Naomi Park, Emma Betteridge, Danni Weldon, Scott Goodwin, Rachel Nelson, Charlotte Beaver, Laura Letchford, David A. Jackson, Luke Foulser, Liz McMinn, Liam Prestwood, Sally Kay, Leanne Kane, Matthew J. Dorman, Inigo Martincorena, 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, Thomas Dibling, Samantha McGuigan, Hazel Rogers, Adam D. Hunter, Emily Souster, Alexandra Neaverson, Ian Goodfellow, Nicholas J. Loman, Oliver G. Pybus, David L. Robertson, Emma C. Thomson, Andrew Rambaut, Thomas R. Connor - Cell 2020 cited by 1,086

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.