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, 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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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Official URL: https://doi.org/10.1016/j.cell.2020.11.020

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.

Item Type: Article
Additional Information: Funding information: We thank all partners and contributors to the COG-UK consortium who are listed at https://www.cogconsortium.uk/about/. We also acknowledge the important work of SARS-CoV-2 genome data producers globally contributing sequence data to the GISAID database and particularly acknowledge the groups who have generated data used by this project, listed in Table S4. E.V. acknowledges the MRC Centre for Global Infectious Disease Analysis (MR/R015600/1). R. Johnson and E.V. acknowledge funding from the European Commission (CoroNAb 101003653). V.H. was supported by the Biotechnology and Biological Sciences Research Council (BBSRC) (grant no. BB/M010996/1). J.T.M., R.M.C., N.J.L., and A.R. acknowledge the support of the Wellcome Trust (Collaborators Award 206298/Z/17/Z – ARTIC network). A.R. is supported by the European Research Council (grant agreement no. 725422 – ReservoirDOCS). D.L.R., A.d.S.F., and E.C.T. are supported by the MRC (MC_UU_1201412). J. Southgate was supported by the BBSRC-funded South West Biosciences Doctoral Training Partnership (training grant reference BB/M009122/1). T.R.C. and N.J.L. acknowledge support from the MRC, which funded computational resources used by the project (grant reference MR/L015080/1). T.R.C. acknowledges funding as part of the BBSRC Institute Strategic Programme Microbes in the Food Chain (BB/R012504/1) and its constituent projects (BBS/E/F/000PR10348 and BBS/E/F/000PR10352). A.P. and T.R.C. acknowledge support from Supercomputing Wales, which is partially funded by the European Regional Development Fund (ERDF) via Welsh Government. The project was also supported by specific funding from Welsh Government, which provided funds for the sequencing and analysis of a subset of the Welsh samples used in this study, via Genomics Partnership Wales.
Uncontrolled Keywords: COVID-19, SARS-CoV-2, evolution, founder effect, epidemiology, spike
Subjects: A300 Clinical Medicine
B100 Anatomy, Physiology and Pathology
C500 Microbiology
C700 Molecular Biology, Biophysics and Biochemistry
Department: Faculties > Health and Life Sciences > Applied Sciences
Depositing User: Elena Carlaw
Date Deposited: 04 Jan 2021 15:09
Last Modified: 27 Jul 2021 13:57
URI: http://nrl.northumbria.ac.uk/id/eprint/45077

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