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

Volz, Erik, Hill, Verity, McCrone, John T., Price, Anna, Jorgensen, David, O’Toole, Áine, Southgate, Joel, Johnson, Robert, Jackson, Ben, Nascimento, Fabricia F., Rey, Sara M., Nicholls, Samuel M., Colquhoun, Rachel M., da Silva Filipe, Ana, Shepherd, James, Pascall, David J., Shah, Rajiv, Jesudason, Natasha, Li, Kathy, Jarrett, Ruth, Pacchiarini, Nicole, Bull, Matthew, Geidelberg, Lily, Siveroni, Igor, Goodfellow, Ian, Loman, Nicholas J., Pybus, Oliver G., Robertson, David L., Thomson, Emma C., Rambaut, Andrew, Connor, Thomas R., Koshy, Cherian, Wise, Emma, Cortes, Nick, Lynch, Jessica, Kidd, Stephen, Mori, Matilde, Fairley, Derek J., Curran, Tanya, McKenna, James P., Adams, Helen, Fraser, Christophe, Golubchik, Tanya, Bonsall, David, Moore, Catrin, Caddy, Sarah L., Khokhar, Fahad A., Wantoch, Michelle, Reynolds, Nicola, Warne, Ben, Maksimovic, Joshua, Spellman, Karla, McCluggage, Kathryn, John, Michaela, Beer, Robert, Afifi, Safiah, Morgan, Sian, Marchbank, Angela, Price, Anna, Kitchen, Christine, Gulliver, Huw, Merrick, Ian, Southgate, Joel, Guest, Martyn, Munn, Robert, Workman, Trudy, Connor, Thomas R., Fuller, William, Bresner, Catherine, Snell, Luke B., Charalampous, Themoula, Nebbia, Gaia, Batra, Rahul, Edgeworth, Jonathan, Robson, Samuel C., Beckett, Angela, Loveson, Katie F., Aanensen, David M., Underwood, Anthony P., Yeats, Corin A., Abudahab, Khalil, Taylor, Ben E.W., Menegazzo, Mirko, Clark, Gemma, Smith, Wendy, Khakh, Manjinder, Fleming, Vicki M., Lister, Michelle M., Howson-Wells, Hannah C., Berry, Louise, Boswell, Tim, Joseph, Amelia, Willingham, Iona, Bird, Paul, Helmer, Thomas, Fallon, Karlie, Holmes, Christopher, Tang, Julian, Raviprakash, Veena, Campbell, Sharon, Sheriff, Nicola, Loose, Matthew W., Holmes, Nadine, Moore, Christopher, Carlile, Matthew, Wright, Victoria, Sang, Fei, Debebe, Johnny, Coll, Francesc, Signell, Adrian W., Betancor, Gilberto, Wilson, Harry D., Feltwell, Theresa, Houldcroft, Charlotte J., Eldirdiri, Sahar, Kenyon, Anita, Davis, Thomas, Pybus, Oliver, du Plessis, Louis, Zarebski, Alex, Raghwani, Jayna, Kraemer, Moritz, Francois, Sarah, Attwood, Stephen, Vasylyeva, Tetyana, Torok, M. Estee, Hamilton, William L., Goodfellow, Ian G., Hall, Grant, Jahun, Aminu S., Chaudhry, Yasmin, Hosmillo, Myra, Pinckert, Malte L., Georgana, Iliana, Yakovleva, Anna, Meredith, Luke W., Moses, Samuel, Lowe, Hannah, Ryan, Felicity, Fisher, Chloe L., Awan, Ali R., Boyes, John, Breuer, Judith, Harris, Kathryn Ann, Brown, Julianne Rose, Shah, Divya, Atkinson, Laura, Lee, Jack C.D., Alcolea-Medina, Adela, Moore, Nathan, Cortes, Nicholas, Williams, Rebecca, Chapman, Michael R., Levett, Lisa J., Heaney, Judith, Smith, Darren, Bashton, Matthew, Young, Gregory R., Allan, John, Loh, Joshua, Randell, Paul A., Cox, Alison, Madona, Pinglawathee, Holmes, Alison, Bolt, Frances, Price, James, Mookerjee, Siddharth, Rowan, Aileen, Taylor, Graham P., Ragonnet-Cronin, Manon, Nascimento, Fabricia F., Jorgensen, David, Siveroni, Igor, Johnson, Rob, Boyd, Olivia, Geidelberg, Lily, Volz, Erik M., Brunker, Kirstyn, Smollett, Katherine L., Loman, Nicholas J., Quick, Joshua, McMurray, Claire, Stockton, Joanne, Nicholls, Sam, Rowe, Will, Poplawski, Radoslaw, Martinez-Nunez, Rocio T., Mason, Jenifer, Robinson, Trevor I., O'Toole, Elaine, Watts, Joanne, Breen, Cassie, Cowell, Angela, Ludden, Catherine, Sluga, Graciela, Machin, Nicholas W., Ahmad, Shazaad S.Y., George, Ryan P., Halstead, Fenella, Sivaprakasam, Venkat, Thomson, Emma C., Shepherd, James G., Asamaphan, Patawee, Niebel, Marc O., Li, Kathy K., Shah, Rajiv N., Jesudason, Natasha G., Parr, Yasmin A., Tong, Lily, Broos, Alice, Mair, Daniel, Nichols, Jenna, Carmichael, Stephen N., Nomikou, Kyriaki, Aranday-Cortes, Elihu, Johnson, Natasha, Starinskij, Igor, da Silva Filipe, Ana, Robertson, David L., Orton, Richard J., Hughes, Joseph, Vattipally, Sreenu, Singer, Joshua B., Hale, Antony D., Macfarlane-Smith, Louissa R., Harper, Katherine L., Taha, Yusri, Payne, Brendan A.I., Burton-Fanning, Shirelle, Waugh, Sheila, Collins, Jennifer, Eltringham, Gary, Templeton, Kate E., McHugh, Martin P., Dewar, Rebecca, Wastenge, Elizabeth, Dervisevic, Samir, Stanley, Rachael, Prakash, Reenesh, Stuart, Claire, Elumogo, Ngozi, Sethi, Dheeraj K., Meader, Emma J., Coupland, Lindsay J., Potter, Will, Graham, Clive, Barton, Edward, Padgett, Debra, Scott, Garren, Swindells, Emma, Greenaway, Jane, Nelson, Andrew, Yew, Wen C., Resende Silva, Paola C., Andersson, Monique, Shaw, Robert, Peto, Timothy, Justice, Anita, Eyre, David, Crooke, Derrick, Hoosdally, Sarah, Sloan, Tim J., Duckworth, Nichola, Walsh, Sarah, Chauhan, Anoop J., Glaysher, Sharon, Bicknell, Kelly, Wyllie, Sarah, Butcher, Ethan, Elliott, Scott, Lloyd, Allyson, Impey, Robert, Levene, Nick, Monaghan, Lynn, Bradley, Declan T., Allara, Elias, Pearson, Clare, Muir, Peter, Vipond, Ian B., Hopes, Richard, Pymont, Hannah M., Hutchings, Stephanie, Curran, Martin D., Parmar, Surendra, Lackenby, Angie, Mbisa, Tamyo, Platt, Steven, Miah, Shahjahan, Bibby, David, Manso, Carmen, Hubb, Jonathan, Chand, Meera, Dabrera, Gavin, Ramsay, Mary, Bradshaw, Daniel, Thornton, Alicia, Myers, Richard, Schaefer, Ulf, Groves, Natalie, Gallagher, Eileen, Lee, David, Williams, David, Ellaby, Nicholas, Harrison, Ian, Hartman, Hassan, Manesis, Nikos, Patel, Vineet, Bishop, Chloe, Chalker, Vicki, Osman, Husam, Bosworth, Andrew, Robinson, Esther, Holden, Matthew T.G., Shaaban, Sharif, Birchley, Alec, Adams, Alexander, Davies, Alisha, Gaskin, Amy, Plimmer, Amy, Gatica-Wilcox, Bree, McKerr, Caoimhe, Moore, Catherine, Williams, Chris, Heyburn, David, De Lacy, Elen, Hilvers, Ember, Downing, Fatima, Shankar, Giri, Jones, Hannah, Asad, Hibo, Coombes, Jason, Watkins, Joanne, Evans, Johnathan M., Fina, Laia, Gifford, Laura, Gilbert, Lauren, Graham, Lee, Perry, Malorie, Morgan, Mari, Bull, Matthew, Cronin, Michelle, Pacchiarini, Nicole, Craine, Noel, Jones, Rachel, Howe, Robin, Corden, Sally, Rey, Sara, Kumziene-Summerhayes, Sara, Taylor, Sarah, Cottrell, Simon, Jones, Sophie, Edwards, Sue, O’Grady, Justin, Page, Andrew J., Wain, John, Webber, Mark A., Mather, Alison E., Baker, David J., Rudder, Steven, Yasir, Muhammad, Thomson, Nicholas M., Aydin, Alp, Tedim, Ana P., Kay, Gemma L., Trotter, Alexander J., Gilroy, Rachel A.J., Alikhan, Nabil-Fareed, de Oliveira Martins, Leonardo, Le-Viet, Thanh, Meadows, Lizzie, Kolyva, Anastasia, Diaz, Maria, Bell, Andrew, Gutierrez, Ana Victoria, Charles, Ian G., Adriaenssens, Evelien M., Kingsley, Robert A., Casey, Anna, Simpson, David A., Molnar, Zoltan, Thompson, Thomas, Acheson, Erwan, Masoli, Jane A.H., Knight, Bridget A., Hattersley, Andrew, Ellard, Sian, Auckland, Cressida, Mahungu, Tabitha W., Irish-Tavares, Dianne, Haque, Tanzina, Bourgeois, Yann, Scarlett, Garry P., Partridge, David G., Raza, Mohammad, Evans, Cariad, Johnson, Kate, Liggett, Steven, Baker, Paul, Essex, Sarah, Lyons, Ronan A., Caller, Laura G., Castellano, Sergi, Williams, Rachel J., Kristiansen, Mark, Roy, Sunando, Williams, Charlotte A., Dyal, Patricia L., Tutill, Helena J., Panchbhaya, Yasmin N., Forrest, Leysa M., Niola, Paola, Findlay, Jacqueline, Brooks, Tony T., Gavriil, Artemis, Mestek-Boukhibar, Lamia, Weeks, Sam, Pandey, Sarojini, Berry, Lisa, Jones, Katie, Richter, Alex, Beggs, Andrew, Smith, Colin P., Bucca, Giselda, Hesketh, Andrew R., Harrison, Ewan M., Peacock, Sharon J., Palmer, Sophie, Churcher, Carol M., Bellis, Katherine L., Girgis, Sophia T., Naydenova, Plamena, Blane, Beth, Sridhar, Sushmita, Ruis, Chris, Forrest, Sally, Cormie, Claire, Gill, Harmeet K., Dias, Joana, Higginson, Ellen E., Maes, Mailis, Young, Jamie, Kermack, Leanne M., Hadjirin, Nazreen F., Aggarwal, Dinesh, Griffith, Luke, Swingler, Tracey, Davidson, Rose K., Rambaut, Andrew, Williams, Thomas, Balcazar, Carlos E., Gallagher, Michael D., O'Toole, Áine, Rooke, Stefan, Jackson, Ben, Colquhoun, Rachel, Ashworth, Jordan, Hill, Verity, McCrone, J.T., Scher, Emily, Yu, Xiaoyu, Williamson, Kathleen A., Stanton, Thomas D., Michell, Stephen L., Bewshea, Claire M., Temperton, Ben, Michelsen, Michelle L., Warwick-Dugdale, Joanna, Manley, Robin, Farbos, Audrey, Harrison, James W., Sambles, Christine M., Studholme, David J., Jeffries, Aaron R., Darby, Alistair C., Hiscox, Julian A., Paterson, Steve, Iturriza-Gomara, Miren, Jackson, Kathryn A., Lucaci, Anita O., Vamos, Edith E., Hughes, Margaret, Rainbow, Lucille, Eccles, Richard, Nelson, Charlotte, Whitehead, Mark, Turtle, Lance, Haldenby, Sam T., Gregory, Richard, Gemmell, Matthew, Kwiatkowski, Dominic, de Silva, Thushan I., Smith, Nikki, Angyal, Adrienn, Lindsey, Benjamin B., Groves, Danielle C., Green, Luke R., Wang, Dennis, Freeman, Timothy M., Parker, Matthew D., Keeley, Alexander J., Parsons, Paul J., Tucker, Rachel M., Brown, Rebecca, Wyles, Matthew, Constantinidou, Chrystala, Unnikrishnan, Meera, Ott, Sascha, Cheng, Jeffrey K.J., Bridgewater, Hannah E., Frost, Lucy R., Taylor-Joyce, Grace, Stark, Richard, Baxter, Laura, Alam, Mohammad T., Brown, Paul E., McClure, Patrick C., Chappell, Joseph G., Tsoleridis, Theocharis, Ball, Jonathan, Gramatopoulos, Dimitris, Buck, David, Todd, John A., Green, Angie, Trebes, Amy, MacIntyre-Cockett, George, de Cesare, Mariateresa, Langford, Cordelia, Alderton, Alex, Amato, Roberto, Goncalves, Sonia, Jackson, David K., Johnston, Ian, Sillitoe, John, Palmer, Steve, Lawniczak, Mara, Berriman, Matt, Danesh, John, Livett, Rich, Shirley, Lesley, Farr, Ben, Quail, Mike, Thurston, Scott, Park, Naomi, Betteridge, Emma, Weldon, Danni, Goodwin, Scott, Nelson, Rachel, Beaver, Charlotte, Letchford, Laura, Jackson, David A., Foulser, Luke, McMinn, Liz, Prestwood, Liam, Kay, Sally, Kane, Leanne, Dorman, Matthew J., Martincorena, Inigo, Puethe, Christoph, Keatley, Jon-Paul, Tonkin-Hill, Gerry, Smith, Christen, Jamrozy, Dorota, Beale, Mathew A., Patel, Minal, Ariani, Cristina, Spencer-Chapman, Michael, Drury, Eleanor, Lo, Stephanie, Rajatileka, Shavanthi, Scott, Carol, James, Keith, Buddenborg, Sarah K., Berger, Duncan J., Patel, Gaurang, Garcia-Casado, Maria V., Dibling, Thomas, McGuigan, Samantha, Rogers, Hazel A., Hunter, Adam D., Souster, Emily and Neaverson, Alexandra S. (2021) Evaluating the Effects of SARS-CoV-2 Spike Mutation D614G on Transmissibility and Pathogenicity. Cell, 184 (1). 64-75.e11. ISSN 0092-8674

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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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