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

作者：Erik Volz, Verity Hill, John T. McCrone, Anna Price, David W. Jorgensen, Aine Niamh O’Toole, Joel Southgate, Robert Johnson, Ben Jackson, Fabrícia Ferreira do Nascimento, Sara M. Rey, Samuel M. Nicholls, Rachel Colquhoun, Ana da Silva Filipe, James G. Shepherd, David J. Pascall, Rajiv N. Shah, Natasha G. Jesudason, Kathy K Li, Ruth F. Jarrett, Nicole Pacchiarini, Matthew J. Bull, Lily Geidelberg, Igor A. Siveroni, Cherian M. Koshy, Emma L. Wise, Nick Cortes, Jessica L. Lynch, Stephen P. Kidd, Matilde Mori, Derek Fairley, Tanya Curran, James Patrick 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 M. Marchbank, Anna Price, Christine Kitchen, Huw Gulliver, Ian Merrick, Joel Southgate, Martyn F. Guest, Robert J. Munn, Trudy Workman, Thomas R. Connor, William H. 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 E. W. Taylor, Mirko Menegazzo, Gemma Clark, Darren Smith, Manjinder Khakh, Vicki M. Fleming, Michelle M. Lister, Hannah C. Howson‐Wells, Louise Berry, Tim C. Boswell, Amelia Joseph, Iona Willingham, Paul William Bird, Thomas Helmer, Karlie Fallon, Christopher W. Holmes, Julian Wei-Tze Tang, Veena Raviprakash, Sharon Campbell, Nicola Sheriff, Matthew Loose, Nadine Holmes, Christopher Moore, Matthew Carlile, Victoria J. Wright, Fei Sang, Johnny Debebe, Francesc Coll, Adrian W. Signell, Gilberto Betancor, Harry David Bruce Wilson, Theresa Feltwell, Charlotte Jane Houldcroft, Sahar Eldirdiri, Anita Kenyon, Thomas Davis, Oliver George 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 D.T. Hosmillo, Malte L. Pinckert, Iliana Georgana, Anna Yakovleva, Luke W. Meredith, Samuel E Moses, Hannah Lowe, Felicity Ryan, Chloe L. Fisher, Ali Raza Awan, John Boyes, Judith Breuer, Kathryn Harris, Julianne Rose Brown, Divya Kelath Shah, Laura Atkinson, Jack C. D. Lee, Adela Alcolea-Medina, Nathan A. Moore, Nicholas J. Cortes, Rebecca J. Williams, Michael Chapman, Lisa J. Levett, Judith Heaney, Darren Smith, Matthew Bashton, Gregory R. Young, John Nathan Allan, Joshua Ping-Yun Loh, Paul Anthony Randell, Alison Dorothea Cox, Pinglawathee Madona, Alison Holmes, Frances Bolt, James Richard Price, Siddharth Mookerjee, Aileen G. Rowan, Graham Philip Taylor, Manon Ragonnet‐Cronin, Fabricia F. Nascimento, David W. Jorgensen, Igor A. Siveroni, Rob Johnson, Olivia Boyd, Lily Geidelberg, Erik Volz, Kirstyn Brunker, Katherine L. Smollett, Nicholas James Loman, Joshua C Quick, Claire L. 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 D. Halstead, Venkat Sivaprakasam, Emma C. Thomson, James G. Shepherd, Patawee Asamaphan, Marc O. Niebel, Kathy K Li, Rajiv N. Shah, Natasha G. Jesudason, Yasmin A. Parr, L. Tong, Alice Broos, Daniel Mair, Jenna Nichols, Stephen N. Carmichael, Kyriaki Nomikou, Elihú Aranday-Cortés, Natasha A. Johnson, Igor Starinskij, Ana da Silva Filipe, David L. Robertson, Richard J Orton, Joseph Hughes, Vattipally B. Sreenu, Joshua B. Singer, Antony D. Hale, Louissa R. Macfarlane-Smith, Katherine L. Harper, Yusri Taha, Brendan A. I. Payne, Shirelle Burton-Fanning, Sheila Waugh, Jennifer M. Collins, Gary Eltringham, Kate E Templeton, Martin P. McHugh, Rebecca Dewar, Elizabeth Wastenge, Samir Dervisevic, Rachael Stanley, Reenesh Prakash, Claire Stuart, Ngozi Elumogo, Dheeraj Sethi, Emma J. Meader, Lindsay J. Coupland, Will Potter, Clive Graham, EDWARD READ BARTON, Debra Padgett, Garren Scott, Emma Swindells, Jane M. Greenaway, Andrew J. Nelson, Wen Chyin Yew, Paola C. Resende Silva, Monique Ingrid Andersson, Robert H. Shaw, Tim Peto, Anita Justice, David W. Eyre, Derrick Crooke, Sarah Hoosdally, Tim John 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 A Chand, Gavin Dabrera, Mary Elizabeth Ramsay, Daniel Bradshaw, Alicia Thornton, Richard E. Myers, Ulf Schaefer, Natalie Groves, Eileen Gallagher, David Lee, David Arnold Williams, Nicholas A.F. Ellaby, Ian Harrison, Hassan B. Hartman, Nikos Manesis, Vineet Indrajit Patel, Chloe Bishop, Vicki Chalker, Husam Kamal Eldin Osman, Andrew Bosworth, Esther Robinson, Matthew T. G. Holden, Sharif Shaaban, Alec Birchley, Alexander Adams, Alisha R 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 Homar Fina, Laura Gifford, Lauren Gilbert, Lee Graham, Malorie Perry, Mari Morgan, Matthew J. Bull, Michelle A. Cronin, Nicole Pacchiarini, Noel Craine, Rachel N. Jones, Robin A. Howe, Sally A. Corden, Sara M. Rey, Sara Kumziene-Summerhayes, Sarah Ann Taylor, Simon L. Cottrell, Sophie Jones, Sue Edwards, Justin O’Grady, Andrew J. Page, John R. Wain, Mark Alexander Webber, Alison E. Mather, David Baker, Steven J. Rudder, Muhammad Yasir, Nicholas M. Thomson, Alp Aydin, Ana P. Tedim, Gemma L. Kay, Alexander J. Trotter, Rachel A. J. 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 A. C. Simpson, Zoltán Molnár, Thomas Thompson, Erwan Acheson, Jane A. H. Masoli, Bridget Knight, Andrew Tym Hattersley, Sian Ellard, Cressida Auckland, Tabitha W. Mahungu, Dianne Irish-Tavares, Tanzina Haque, Yann Bourgeois, Garry P. Scarlett, David George Partridge, Mohammad Raza, Cariad M. Evans, KATE JOHNSON, Steven Liggett, Paul N. Baker, Sarah J. Essex, Ronan Anthony Lyons, Laura Caller, Sergi Castellano, Rachel J. Williams, Mark Kristiansen, Sunando Roy, Charlotte A. Williams, Patricia L. Dyal, Helena J. Tutill, Yasmin Panchbhaya, Leysa Forrest, Paola Niola, Jacqueline Findlay, T Brooks, Artemis Gavriil, Lamia Mestek, Sam Weeks, Sarojini Pandey, Lisa K. Berry, Katie E. Jones, Alex Richter, Andrew David Beggs, Colin P. Sambrook Smith, Giselda Bucca, Andrew R. Hesketh, Ewan M. Harrison, Sharon J. Peacock, Sophie Palmer, Carol M. 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 K. 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, Aine Niamh 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 John Studholme, Aaron R. Jeffries, Alistair C. Darby, Julian A. Hiscox, Steve Paterson, Miren Iturriza-Gomara, Kathryn A. V. Jackson, Anita O. Lucaci, Edith E. Vamos, Margaret Hughes, Lucille Rainbow, Richard M. Eccles, Charlotte L. Nelson, Mark A Whitehead, Lance C. W. Turtle, Sam T. Haldenby, Richard I. Gregory, Matthew Gemmell, Dominic P. Kwiatkowski, Thushan I. de Silva, Darren Smith, Adrienn Angyal, Benjamin B. Lindsey, Danielle C. Groves, Luke R. Green, Dennis Y.Q. Wang, Timothy M. Freeman, Matthew D. Parker, Alexander James Keeley, Paul J. Parsons, Rachel M. Tucker, Rebecca J. 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 A. Baxter, Mohammad Tauqeer Alam, Paul E. Brown, C. Patrick McClure, Joseph G. Chappell, Theocharis Tsoleridis, Jonathan K. Ball, Dimitris K 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 Kelly Jackson, Ian Johnston, John Sillitoe, Steve Palmer, Mara Lawniczak, Matthew Berriman, John Danesh, Rich Livett, Lesley Shirley, Ben W. Farr, Mike A. Quail, Scott Thurston, Naomi Park, Emma Betteridge, Danni Weldon, Scott Craig 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 Q. Tonkin‐Hill, Christen Smith, Dorota M. Jamrozy, Mathew A. Beale, Minal K. Patel, Cristina V. Ariani, Michael Spencer-Chapman, Eleanor Drury, Stephanie W. Lo, Shavanthi Rajatileka, Carol Scott, Keith E. James, Sarah K. Buddenborg, Duncan Berger, Gaurang Patel, Maria V. Garcia-Casado, Thomas Dibling, Samantha McGuigan, Hazel Anne Rogers, Adam D. Hunter, Emily Souster, Alexandra Neaverson, Ian Goodfellow, Nicholas James Loman, Oliver George Pybus, David L. Robertson, Emma C. Thomson, Andrew Rambaut, Thomas R. Connor · 发表于：Cell · 年份：2020 · DOI：10.1016/j.cell.2020.11.020 · 被引用次数：1087 · 研究领域：SARS-CoV-2 and COVID-19 Research、COVID-19 Clinical Research Studies、COVID-19 epidemiological studies

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.