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1. Effect of second booster vaccinations and prior infection against SARS-CoV-2 in the UK SIREN healthcare worker cohortResearch in context

Author

Peter D. Kirwan, Victoria J. Hall, Sarah Foulkes, Ashley D. Otter, Katie Munro, Dominic Sparkes, Anna Howells, Naomi Platt, Jonathan Broad, David Crossman, Chris Norman, Diane Corrigan, Christopher H. Jackson, Michelle Cole, Colin S. Brown, Ana Atti, Jasmin Islam, Anne M. Presanis, Andre Charlett, Daniela De Angelis, Susan Hopkins, Tracy Lewis, Steve Bain, Rebeccah Thomas, John Geen, Carla Pothecary, Sean Cutler, John Northfield, Cathy Price, Johanne Tomlinson, Sarah Knight, Emily Macnaughton, Ekaterina Watson, Rajeka Lazarus, Aaran Sinclair, Joanne Galliford, Bridgett Masunda, Tabitha Mahungu, Alison Rodger, Esther Hanison, Simon Warren, Swati Jain, Mariyam Mirfenderesky, Natasha Mahabir, Rowan Pritchard-Jones, Diane Wycherley, Claire Gabriel, Elijah Matovu, Philippa Bakker, Simantee Guha, S. Gormley, James Pethick, Georgina Butt, Stacey Pepper, Luke Bedford, Paul Ridley, Jane Democratis, Manjula Meda, Anu Chawla, Fran Westwell, Nagesh Kalakonda, Sheena Khanduri, Allison Doel, Sumita Pai, Christian Hacon, Davis Nwaka, Veronica Mendez Moro, A. Moody, Cressida Auckland, Stephanie Prince, Thushan de Silva, Helen Shulver, A. Shah, C. Jones, Banerjee Subhro-Osuji, Angela Houston, Tim Planche, Martin Booth, Christopher Duff, Jonnie Aeron-Thomas, Ray Chaudhuri, David Hilton, Hannah Jory, Zehra'a Al-Khafaji, Philippa Kemsley, Ruth Longfellow, David Boss, Simon Brake, Louise Coke, Ngozi Elumogo, Scott Latham, Chinari Subudhi, Ina Hoad, Claire Thomas, Nihil Chitalia, Tracy Edmunds, Helen Ashby, John Elliott, Beverley Wilkinson, Abby Rand, Catherine Thompson, K. Agwuh, Anna Grice, Kelly Moran, Vijayendra Waykar, Yvonne Lester, Lauren Sach, Kathryn Court, Nikki White, Clair Favager, Kyra Holliday, Jayne Harwood, Brendan Payne, Karen Burns, Lynda Fothergill, Alejandro Arenas-Pinto, Abigail Severn, Kerryanne Brown, Katherine Gray, Jane Dare, Qi Zheng, Kathryn Hollinshead, Robert Shorten, Alun Roebuck, Christopher Holmes, Martin Wiselka, Barzo Faris, Liane Marsh, Clare McAdam, Lisa Ditchfield, Zaman Qazzafi, G. Boyd, N. Wong, Sarah Brand, Jack Squires, John Ashcroft, Ismaelette Del Rosario, Joanne Howard, Emma Ward, Gemma Harrison, Joely Morgan, Claire Corless, Ruth Penn, Nick Wong, Manny Bagary, Nadezda Starkova, Mandy Beekes, Mandy Carnahan, Shivani Khan, Shekoo Mackay, Keneisha Lewis, Graham Pickard, Joy Dawson, Lauren Finlayson, Euan Cameron, Anne Todd, Sebastien Fagegaltier, Sally Mavin, Alexandra Cochrane, Andrew Gibson, Sam Donaldson, Kate Templeton, Martin Malcolm, Beth Smith, Devesh Dhasmana, Susan Fowler, Antonia Ho, Michael Murphy, Claire Beith, Manish Patel, Elizabeth Boyd, Val Irvine, Alison Grant, Rebecca Temple-Purcell, Clodagh Loughrey, Elinor Hanna, Frances Johnston, Angel Boulos, Fiona Thompson, Yuri Protaschik, Susan Regan, Tracy Donaghy, Maurice O'Kane, Omolola Akinbami, Paola Barbero, Tim Brooks, Meera Chand, Ferdinando Insalata, Palak Joshi, Anne-Marie O'Connell, Mary Ramsay, Ayoub Saei, Maria Zambon, Ezra Linley, Simon Tonge, Enemona Adaji, Omoyeni Adebiyi, Nick Andrews, Joanna Conneely, Paul Conneely, Angela Dunne, Simone Dyer, Hannah Emmett, Nipunadi Hettiarachchi, Nishanthan Kapirial, Jameel Khawam, Edward Monk, Sophie Russell, Andrew Taylor-Kerr, Jean Timeyin, Silvia D'Arcangelo, Cathy Rowe, Amanda Semper, Eileen Gallagher, Robert Kyffin, Lisa Cromey, Desmond Areghan, Jennifer Bishop, Melanie Dembinsky, Laura Dobbie, Josie Evans, David Goldberg, Lynne Haahr, Annelysse Jorgenson, Ayodeji Matuluko, Laura Naismith, Desy Nuryunarsih, Alexander Olaoye, Caitlin Plank, Lesley Price, Nicole Sergenson, Sally Stewart, Andrew Telfer, Jennifer Weir, Ellen De Lacy, Yvette Ellis, Susannah Froude, Guy Stevens, Linda Tyson, Susanna Dunachie, Paul Klenerman, Chris Duncan, Rebecca Payne, Lance Turtle, Alex Richter, Thushan De Silva, Eleanor Barnes, Daniel Wootton, Oliver Galgut, Jonathan Heeney, Helen Baxendale, Javier Castillo-Olivares, Rupert Beale, Edward Carr, Wendy Barclay, Maya Moshe, Massimo Palmarini, Brian Willett, John Kenneth Baillie, Jennie Evans, and Erika Aquino

Subjects
SARS-CoV-2, Vaccine effectiveness, Asymptomatic, Symptomatic, Healthcare worker, Cohort study, Public aspects of medicine, RA1-1270
Abstract

Summary: Background: The protection of fourth dose mRNA vaccination against SARS-CoV-2 is relevant to current global policy decisions regarding ongoing booster roll-out. We aimed to estimate the effect of fourth dose vaccination, prior infection, and duration of PCR positivity in a highly-vaccinated and largely prior-COVID-19 infected cohort of UK healthcare workers. Methods: Participants underwent fortnightly PCR and regular antibody testing for SARS-CoV-2 and completed symptoms questionnaires. A multi-state model was used to estimate vaccine effectiveness (VE) against infection from a fourth dose compared to a waned third dose, with protection from prior infection and duration of PCR positivity jointly estimated. Findings: 1298 infections were detected among 9560 individuals under active follow-up between September 2022 and March 2023. Compared to a waned third dose, fourth dose VE was 13.1% (95% CI 0.9 to 23.8) overall; 24.0% (95% CI 8.5 to 36.8) in the first 2 months post-vaccination, reducing to 10.3% (95% CI −11.4 to 27.8) and 1.7% (95% CI −17.0 to 17.4) at 2–4 and 4–6 months, respectively. Relative to an infection >2 years ago and controlling for vaccination, 63.6% (95% CI 46.9 to 75.0) and 29.1% (95% CI 3.8 to 43.1) greater protection against infection was estimated for an infection within the past 0–6, and 6–12 months, respectively. A fourth dose was associated with greater protection against asymptomatic infection than symptomatic infection, whilst prior infection independently provided more protection against symptomatic infection, particularly if the infection had occurred within the previous 6 months. Duration of PCR positivity was significantly lower for asymptomatic compared to symptomatic infection. Interpretation: Despite rapid waning of protection, vaccine boosters remain an important tool in responding to the dynamic COVID-19 landscape; boosting population immunity in advance of periods of anticipated pressure, such as surging infection rates or emerging variants of concern. Funding: UK Health Security Agency, Medical Research Council, NIHR HPRU Oxford, Bristol, and others.

Published
2024
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2. Persistence of clinically relevant levels of SARS-CoV2 envelope gene subgenomic RNAs in non-immunocompromised individuals

Author

Merlin Davies, Laura R Bramwell, Nicola Jeffery, Ben Bunce, Ben P Lee, Bridget Knight, Cressida Auckland, Jane AH Masoli, and Lorna W Harries

Subjects
SARS-COV-2, sgRNA, transmission, persistence, Infectious and parasitic diseases, RC109-216
Abstract

Objectives: This study aimed to evaluate the associations between COVID-19 severity and active viral load, and to characterize the dynamics of active SARS-CoV-2 clearance in a series of archival samples taken from patients in the first wave of COVID-19 infection in the South West of the UK. Methods: Subgenomic RNA (sgRNA) and E-gene genomic sequences were measured in a retrospective collection of PCR-confirmed SARS-CoV-2-positive samples from 176 individuals, and related to disease severity. Viral clearance dynamics were then assessed in relation to symptom onset and last positive test. Results: Whilst E-gene sgRNAs declined before E-gene genomic sequences, some individuals retained sgRNA positivity for up to 68 days. 13% of sgRNA-positive cases still exhibited clinically relevant levels of virus after 10 days, with no clinical features previously associated with prolonged viral clearance times. Conclusions: Our results suggest that potentially active virus can sometimes persist beyond a 10-day period, and could pose a potential risk of onward transmission. Where this would pose a serious public health threat, additional mitigation strategies may be necessary to reduce the risk of secondary cases in vulnerable settings.

Published
2022
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3. The impact of viral mutations on recognition by SARS-CoV-2 specific T cells

Author

Thushan I. de Silva, Guihai Liu, Benjamin B. Lindsey, Danning Dong, Shona C. Moore, Nienyun Sharon Hsu, Dhruv Shah, Dannielle Wellington, Alexander J. Mentzer, Adrienn Angyal, Rebecca Brown, Matthew D. Parker, Zixi Ying, Xuan Yao, Lance Turtle, Susanna Dunachie, Mala K. Maini, Graham Ogg, Julian C. Knight, Yanchun Peng, Sarah L. Rowland-Jones, Tao Dong, David M. Aanensen, Khalil Abudahab, Helen Adams, Alexander Adams, Safiah Afifi, Dinesh Aggarwal, Shazaad S.Y. Ahmad, Louise Aigrain, Adela Alcolea-Medina, Nabil-Fareed Alikhan, Elias Allara, Roberto Amato, Tara Annett, Stephen Aplin, Cristina V. Ariani, Hibo Asad, Amy Ash, Paula Ashfield, Fiona Ashford, Laura Atkinson, Stephen W. Attwood, Cressida Auckland, Alp Aydin, David J. Baker, Paul Baker, Carlos E. Balcazar, Jonathan Ball, Jeffrey C. Barrett, Magdalena Barrow, Edward Barton, Matthew Bashton, Andrew R. Bassett, Rahul Batra, Chris Baxter, Nadua Bayzid, Charlotte Beaver, Angela H. Beckett, Shaun M. Beckwith, Luke Bedford, Robert Beer, Andrew Beggs, Katherine L. Bellis, Louise Berry, Beatrice Bertolusso, Angus Best, Emma Betteridge, David Bibby, Kelly Bicknell, Debbie Binns, Alec Birchley, Paul W. Bird, Chloe Bishop, Rachel Blacow, Victoria Blakey, Beth Blane, Frances Bolt, James Bonfield, Stephen Bonner, David Bonsall, Tim Boswell, Andrew Bosworth, Yann Bourgeois, Olivia Boyd, Declan T. Bradley, Cassie Breen, Catherine Bresner, Judith Breuer, Stephen Bridgett, Iraad F. Bronner, Ellena Brooks, Alice Broos, Julianne R. Brown, Giselda Bucca, Sarah L. Buchan, David Buck, Matthew Bull, Phillipa J. Burns, Shirelle Burton-Fanning, Timothy Byaruhanga, Matthew Byott, Sharon Campbell, Alessandro M. Carabelli, James S. Cargill, Matthew Carlile, Silvia F. Carvalho, Anna Casey, Anibolina Castigador, Jana Catalan, Vicki Chalker, Nicola J. Chaloner, Meera Chand, Joseph G. Chappell, Themoula Charalampous, Wendy Chatterton, Yasmin Chaudhry, Carol M. Churcher, Gemma Clark, Phillip Clarke, Benjamin J. Cogger, Kevin Cole, Jennifer Collins, Rachel Colquhoun, Thomas R. Connor, Kate F. Cook, Jason Coombes, Sally Corden, Claire Cormie, Nicholas Cortes, Marius Cotic, Seb Cotton, Simon Cottrell, Lindsay Coupland, MacGregor Cox, Alison Cox, Noel Craine, Liam Crawford, Aidan Cross, Matthew R. Crown, Dorian Crudgington, Nicola Cumley, Tanya Curran, Martin D. Curran, Ana da Silva Filipe, Gavin Dabrera, Alistair C. Darby, Rose K. Davidson, Alisha Davies, Robert M. Davies, Thomas Davis, Daniela de Angelis, Elen De Lacy, Leonardo de Oliveira Martins, Johnny Debebe, Rebecca Denton-Smith, Samir Dervisevic, Rebecca Dewar, Jayasree Dey, Joana Dias, Donald Dobie, Matthew J. Dorman, Fatima Downing, Megan Driscoll, Louis du Plessis, Nichola Duckworth, Jillian Durham, Kirstine Eastick, Lisa J. Easton, Richard Eccles, Jonathan Edgeworth, Sue Edwards, Kate El Bouzidi, Sahar Eldirdiri, Nicholas Ellaby, Scott Elliott, Gary Eltringham, Leah Ensell, Michelle J. Erkiert, Marina Escalera Zamudio, Sarah Essex, Johnathan M. Evans, Cariad Evans, William Everson, Derek J. Fairley, Karlie Fallon, Arezou Fanaie, Ben W. Farr, Christopher Fearn, Theresa Feltwell, Lynne Ferguson, Laia Fina, Flavia Flaviani, Vicki M. Fleming, Sally Forrest, Ebenezer Foster-Nyarko, Benjamin H. Foulkes, Luke Foulser, Mireille Fragakis, Dan Frampton, Sarah Francois, Christophe Fraser, Timothy M. Freeman, Helen Fryer, Marc Fuchs, William Fuller, Kavitha Gajee, Katerina Galai, Abbie Gallagher, Eileen Gallagher, Michael D. Gallagher, Marta Gallis, Amy Gaskin, Bree Gatica-Wilcox, Lily Geidelberg, Matthew Gemmell, Iliana Georgana, Ryan P. George, Laura Gifford, Lauren Gilbert, Sophia T. Girgis, Sharon Glaysher, Emily J. Goldstein, Tanya Golubchik, Andrea N. Gomes, Sónia Gonçalves, Ian G. Goodfellow, Scott Goodwin, Salman Goudarzi, Marina Gourtovaia, Clive Graham, Lee Graham, Paul R. Grant, Luke R. Green, Angie Green, Jane Greenaway, Richard Gregory, Martyn Guest, Rory N. Gunson, Ravi K. Gupta, Bernardo Gutierrez, Sam T. Haldenby, William L. Hamilton, Samantha E. Hansford, Tanzina Haque, Kathryn A. Harris, Ian Harrison, Ewan M. Harrison, Jennifer Hart, John A. Hartley, William T. Harvey, Matthew Harvey, Mohammed O. Hassan-Ibrahim, Judith Heaney, Thomas Helmer, John H. Henderson, Andrew R. Hesketh, Jessica Hey, David Heyburn, Ellen E. Higginson, Verity Hill, Jack D. Hill, Rachel A. Hilson, Ember Hilvers, Matthew T.G. Holden, Amy Hollis, Christopher W. Holmes, Nadine Holmes, Alison H. Holmes, Richard Hopes, Hailey R. Hornsby, Myra Hosmillo, Catherine Houlihan, Hannah C. Howson-Wells, Jonathan Hubb, Hannah Huckson, Warwick Hughes, Joseph Hughes, Margaret Hughes, Stephanie Hutchings, Giles Idle, Chris J. Illingworth, Robert Impey, Dianne Irish-Tavares, Miren Iturriza-Gomara, Rhys Izuagbe, Chris Jackson, Ben Jackson, Leigh M. Jackson, Kathryn A. Jackson, David K. Jackson, Aminu S. Jahun, Victoria James, Keith James, Christopher Jeanes, Aaron R. Jeffries, Sarah Jeremiah, Andrew Jermy, Michaela John, Rob Johnson, Kate Johnson, Ian Johnston, Owen Jones, Sophie Jones, Hannah Jones, Christopher R. Jones, Neil Jones, Amelia Joseph, Sarah Judges, Gemma L. Kay, Sally Kay, Jon-Paul Keatley, Alexander J. Keeley, Anita Kenyon, Leanne M. Kermack, Manjinder Khakh, Stephen P. Kidd, Maimuna Kimuli, Stuart Kirk, Christine Kitchen, Katie Kitchman, Bridget A. Knight, Cherian Koshy, Moritz U.G. Kraemer, Sara Kumziene-Summerhayes, Dominic Kwiatkowski, Angie Lackenby, Kenneth G. Laing, Temi Lampejo, Cordelia F. Langford, Deborah Lavin, Andrew I. Lawton, Jack Lee, David Lee, Stefanie V. Lensing, Steven Leonard, Lisa J. Levett, Thanh Le-Viet, Jonathan Lewis, Kevin Lewis, Jennifier Liddle, Steven Liggett, Patrick J. Lillie, Michelle M. Lister, Rich Livett, Stephanie Lo, Nicholas J. Loman, Matthew W. Loose, Stavroula F. Louka, Katie F. Loveson, Sarah Lowdon, Hannah Lowe, Helen L. Lowe, Anita O. Lucaci, Catherine Ludden, Jessica Lynch, Ronan A. Lyons, Katrina Lythgoe, Nicholas W. Machin, George MacIntyre-Cockett, Andrew Mack, Ben Macklin, Alasdair Maclean, Emily Macnaughton, Pinglawathee Madona, Mailis Maes, Laurentiu Maftei, Adhyana I.K. Mahanama, Tabitha W. Mahungu, Daniel Mair, Joshua Maksimovic, Cassandra S. Malone, Daniel Maloney, Nikos Manesis, Robin Manley, Anna Mantzouratou, Angela Marchbank, Arun Mariappan, Inigo Martincorena, Rocio T. Martinez Nunez, Alison E. Mather, Patrick Maxwell, Megan Mayhew, Tamyo Mbisa, Clare M. McCann, Shane A. McCarthy, Kathryn McCluggage, Patrick C. McClure, J.T. McCrone, Martin P. McHugh, James P. McKenna, Caoimhe McKerr, Georgina M. McManus, Claire L. McMurray, Claire McMurray, Alan McNally, Lizzie Meadows, Nathan Medd, Oliver Megram, Mirko Menegazzo, Ian Merrick, Stephen L. Michell, Michelle L. Michelsen, Mariyam Mirfenderesky, Jeremy Mirza, Julia Miskelly, Emma Moles-Garcia, Robin J. Moll, Zoltan Molnar, Irene M. Monahan, Matteo Mondani, Siddharth Mookerjee, Christopher Moore, Jonathan Moore, Nathan Moore, Catherine Moore, Helen Morcrette, Sian Morgan, Mari Morgan, Matilde Mori, Arthur Morriss, Samuel Moses, Craig Mower, Peter Muir, Afrida Mukaddas, Florence Munemo, Robert Munn, Abigail Murray, Leanne J. Murray, Darren R. Murray, Manasa Mutingwende, Richard Myers, Eleni Nastouli, Gaia Nebbia, Andrew Nelson, Charlotte Nelson, Sam Nicholls, Jenna Nichols, Roberto Nicodemi, Kyriaki Nomikou, Justin O’Grady, Sarah O'Brien, Mina Odedra, Natasha Ohemeng-Kumi, Karen Oliver, Richard J. Orton, Husam Osman, xeine O'Toole, Nicole Pacchiarini, Debra Padgett, Andrew J. Page, Emily J. Park, Naomi R. Park, Surendra Parmar, David G. Partridge, David Pascall, Amita Patel, Bindi Patel, Steve Paterson, Brendan A.I. Payne, Sharon J. Peacock, Clare Pearson, Emanuela Pelosi, Benita Percival, Jon Perkins, Malorie Perry, Malte L. Pinckert, Steven Platt, Olga Podplomyk, Manoj Pohare, Marcus Pond, Cassie F. Pope, Radoslaw Poplawski, Jessica Powell, Jennifer Poyner, Liam Prestwood, Anna Price, James R. Price, Jacqui A. Prieto, David T. Pritchard, Sophie J. Prosolek, Georgia Pugh, Monika Pusok, Oliver G. Pybus, Hannah M. Pymont, Michael A. Quail, Joshua Quick, Clara Radulescu, Jayna Raghwani, Manon Ragonnet-Cronin, Lucille Rainbow, Diana Rajan, Shavanthi Rajatileka, Newara A. Ramadan, Andrew Rambaut, John Ramble, Paul A. Randell, Paul Randell, Liz Ratcliffe, Veena Raviprakash, Mohammad Raza, Nicholas M. Redshaw, Sara Rey, Nicola Reynolds, Alex Richter, David L. Robertson, Esther Robinson, Samuel C. Robson, Fiona Rogan, Stefan Rooke, Will Rowe, Sunando Roy, Steven Rudder, Chris Ruis, Steven Rushton, Felicity Ryan, Kordo Saeed, Buddhini Samaraweera, Christine M. Sambles, Roy Sanderson, Theo Sanderson, Fei Sang, Thea Sass, Emily Scher, Garren Scott, Carol Scott, Jasveen Sehmi, Sharif Shaaban, Divya Shah, Jessica Shaw, Ekaterina Shelest, James G. Shepherd, Liz A. Sheridan, Nicola Sheriff, Lesley Shirley, John Sillitoe, Siona Silviera, David A. Simpson, Aditi Singh, Dawn Singleton, Timofey Skvortsov, Tim J. Sloan, Graciela Sluga, Ken Smith, Kim S. Smith, Perminder Smith, Darren L. Smith, Louise Smith, Colin P. Smith, Nikki Smith, Katherine L. Smollett, Luke B. Snell, Thomas Somassa, Joel Southgate, Karla Spellman, Michael H. Spencer Chapman, Lewis G. Spurgin, Moira J. Spyer, Rachael Stanley, William Stanley, Thomas D. Stanton, Igor Starinskij, Joanne Stockton, Susanne Stonehouse, Nathaniel Storey, David J. Studholme, Malur Sudhanva, Emma Swindells, Yusri Taha, Ngee Keong Tan, Julian W. Tang, Miao Tang, Ben E.W. Taylor, Joshua F. Taylor, Sarah Taylor, Ben Temperton, Kate E. Templeton, Claire Thomas, Laura Thomson, Emma C. Thomson, Alicia Thornton, Scott A.J. Thurston, John A. Todd, Rachael Tomb, Lily Tong, Gerry Tonkin-Hill, M. Estee Torok, Jaime M. Tovar-Corona, Amy Trebes, Alexander J. Trotter, Ioulia Tsatsani, Robyn Turnbull, Katherine A. Twohig, Helen Umpleby, Anthony P. Underwood, Edith E. Vamos, Tetyana I. Vasylyeva, Sreenu Vattipally, Gabrielle Vernet, Barry B. Vipond, Erik M. Volz, Sarah Walsh, Dennis Wang, Ben Warne, Joanna Warwick-Dugdale, Elizabeth Wastnedge, Joanne Watkins, Louisa K. Watson, Sheila Waugh, Hermione J. Webster, Danni Weldon, Elaine Westwick, Thomas Whalley, Helen Wheeler, Mark Whitehead, Max Whiteley, Andrew Whitwham, Claudia Wierzbicki, Nicholas J. Willford, Lesley-Anne Williams, Rebecca Williams, Cheryl Williams, Chris Williams, Charlotte A. Williams, Rachel J. Williams, Thomas Williams, Catryn Williams, Kathleen A. Williamson, Eleri Wilson-Davies, Eric Witele, Karen T. Withell, Adam A. Witney, Paige Wolverson, Nick Wong, Trudy Workman, Victoria Wright, Derek W. Wright, Tim Wyatt, Sarah Wyllie, Li Xu-McCrae, Mehmet Yavus, Geraldine Yaze, Corin A. Yeats, Gonzalo Yebra, Wen C. Yew, Gregory R. Young, Jamie Young, Alex E. Zarebski, Peijun Zhang, J. Kenneth Baillie, Malcolm G. Semple, Peter J.M. Openshaw, Gail Carson, Beatrice Alex, Petros Andrikopoulos, Benjamin Bach, Wendy S. Barclay, Debby Bogaert, Kanta Chechi, Graham S. Cooke, Annemarie B. Docherty, Gonçalo dos Santos Correia, Marc-Emmanuel Dumas, Jake Dunning, Tom Fletcher, Christopher A. Green, William Greenhalf, Julian L. Griffin, Rishi K. Gupta, Ewen M. Harrison, Julian A. Hiscox, Antonia Ying Wai Ho, Peter W. Horby, Samreen Ijaz, Saye Khoo, Paul Klenerman, Andrew Law, Matthew R. Lewis, Sonia Liggi, Wei Shen Lim, Lynn Maslen, Laura Merson, Alison M. Meynert, Mahdad Noursadeghi, Michael Olanipekun, Anthonia Osagie, Massimo Palmarini, Carlo Palmieri, William A. Paxton, Georgios Pollakis, Nicholas Price, Clark D. Russell, Vanessa Sancho-Shimizu, Caroline J. Sands, Janet T. Scott, Louise Sigfrid, Tom Solomon, Shiranee Sriskandan, David Stuart, Charlotte Summers, Olivia V. Swann, Zoltan Takats, Panteleimon Takis, Richard S. Tedder, A.A. Roger Thompson, Ryan S. Thwaites, Maria Zambon, Hayley Hardwick, Chloe Donohue, Fiona Griffiths, Wilna Oosthuyzen, Cara Donegan, Rebecca G. Spencer, Jo Dalton, Michelle Girvan, Egle Saviciute, Stephanie Roberts, Janet Harrison, Laura Marsh, Marie Connor, Sophie Halpin, Clare Jackson, Carrol Gamble, Daniel Plotkin, James Lee, Gary Leeming, Murray Wham, Sara Clohisey, Ross Hendry, James Scott-Brown, Victoria Shaw, Sarah E. McDonald, Seán Keating, Katie A. Ahmed, Jane A. Armstrong, Milton Ashworth, Innocent G. Asiimwe, Siddharth Bakshi, Samantha L. Barlow, Laura Booth, Benjamin Brennan, Katie Bullock, Benjamin W.A. Catterall, Jordan J. Clark, Emily A. Clarke, Sarah Cole, Louise Cooper, Helen Cox, Christopher Davis, Oslem Dincarslan, Chris Dunn, Philip Dyer, Angela Elliott, Anthony Evans, Lorna Finch, Lewis W.S. Fisher, Terry Foster, Isabel Garcia-Dorival, Philip Gunning, Catherine Hartley, Rebecca L. Jensen, Christopher B. Jones, Trevor R. Jones, Shadia Khandaker, Katharine King, Robyn T. Kiy, Chrysa Koukorava, Annette Lake, Suzannah Lant, Diane Latawiec, Lara Lavelle-Langham, Daniella Lefteri, Lauren Lett, Lucia A. Livoti, Maria Mancini, Sarah McDonald, Laurence McEvoy, John McLauchlan, Soeren Metelmann, Nahida S. Miah, Joanna Middleton, Joyce Mitchell, Ellen G. Murphy, Rebekah Penrice-Randal, Jack Pilgrim, Tessa Prince, Will Reynolds, P. Matthew Ridley, Debby Sales, Victoria E. Shaw, Rebecca K. Shears, Benjamin Small, Krishanthi S. Subramaniam, Agnieska Szemiel, Aislynn Taggart, Jolanta Tanianis-Hughes, Jordan Thomas, Erwan Trochu, Libby van Tonder, Eve Wilcock, J. Eunice Zhang, Lisa Flaherty, Nicole Maziere, Emily Cass, Alejandra Doce Carracedo, Nicola Carlucci, Anthony Holmes, Hannah Massey, Lee Murphy, Nicola Wrobel, Sarah McCafferty, Kirstie Morrice, Alan MacLean, Kayode Adeniji, Daniel Agranoff, Ken Agwuh, Dhiraj Ail, Erin L. Aldera, Ana Alegria, Sam Allen, Brian Angus, Abdul Ashish, Dougal Atkinson, Shahedal Bari, Gavin Barlow, Stella Barnass, Nicholas Barrett, Christopher Bassford, Sneha Basude, David Baxter, Michael Beadsworth, Jolanta Bernatoniene, John Berridge, Colin Berry, Nicola Best, Pieter Bothma, David Chadwick, Robin Brittain-Long, Naomi Bulteel, Tom Burden, Andrew Burtenshaw, Vikki Caruth, Duncan Chambler, Nigel Chee, Jenny Child, Srikanth Chukkambotla, Tom Clark, Paul Collini, Catherine Cosgrove, Jason Cupitt, Maria-Teresa Cutino-Moguel, Paul Dark, Chris Dawson, Phil Donnison, Sam Douthwaite, Andrew Drummond, Ingrid DuRand, Ahilanadan Dushianthan, Tristan Dyer, Chi Eziefula, Chrisopher Fegan, Adam Finn, Duncan Fullerton, Sanjeev Garg, Atul Garg, Effrossyni Gkrania-Klotsas, Jo Godden, Arthur Goldsmith, Elaine Hardy, Stuart Hartshorn, Daniel Harvey, Peter Havalda, Daniel B. Hawcutt, Maria Hobrok, Luke Hodgson, Anil Hormis, Michael Jacobs, Susan Jain, Paul Jennings, Agilan Kaliappan, Vidya Kasipandian, Stephen Kegg, Michael Kelsey, Jason Kendall, Caroline Kerrison, Ian Kerslake, Oliver Koch, Gouri Koduri, George Koshy, Shondipon Laha, Steven Laird, Susan Larkin, Tamas Leiner, Patrick Lillie, James Limb, Vanessa Linnett, Jeff Little, Mark Lyttle, Michael MacMahon, Emily MacNaughton, Ravish Mankregod, Huw Masson, Elijah Matovu, Katherine McCullough, Ruth McEwen, Manjula Meda, Gary Mills, Jane Minton, Kavya Mohandas, Quen Mok, James Moon, Elinoor Moore, Patrick Morgan, Craig Morris, Katherine Mortimore, Mbiye Mpenge, Rohinton Mulla, Michael Murphy, Megan Nagel, Thapas Nagarajan, Mark Nelson, Lillian Norris, Matthew K. O'Shea, Igor Otahal, Marlies Ostermann, Mark Pais, Selva Panchatsharam, Danai Papakonstantinou, Hassan Paraiso, Brij Patel, Natalie Pattison, Justin Pepperell, Mark Peters, Mandeep Phull, Stefania Pintus, Jagtur Singh Pooni, Tim Planche, Frank Post, David Price, Rachel Prout, Nikolas Rae, Henrik Reschreiter, Tim Reynolds, Neil Richardson, Mark Roberts, Devender Roberts, Alistair Rose, Guy Rousseau, Bobby Ruge, Brendan Ryan, Taranprit Saluja, Matthias L. Schmid, Aarti Shah, Prad Shanmuga, Anil Sharma, Anna Shawcross, Jeremy Sizer, Manu Shankar-Hari, Richard Smith, Catherine Snelson, Nick Spittle, Nikki Staines, Tom Stambach, Richard Stewart, Pradeep Subudhi, Tamas Szakmany, Kate Tatham, Jo Thomas, Chris Thompson, Robert Thompson, Ascanio Tridente, Darell Tupper-Carey, Mary Twagira, Nick Vallotton, Rama Vancheeswaran, Lisa Vincent-Smith, Shico Visuvanathan, Alan Vuylsteke, Sam Waddy, Rachel Wake, Andrew Walden, Ingeborg Welters, Tony Whitehouse, Paul Whittaker, Ashley Whittington, Padmasayee Papineni, Meme Wijesinghe, Martin Williams, Lawrence Wilson, Stephen Winchester, Martin Wiselka, Adam Wolverson, Daniel G. Wootton, Andrew Workman, Bryan Yates, and Peter Young

Subjects
Phylogenetics, Molecular biology, Immunology, Immune response, Virology, Science
Abstract

Summary: We identify amino acid variants within dominant SARS-CoV-2 T cell epitopes by interrogating global sequence data. Several variants within nucleocapsid and ORF3a epitopes have arisen independently in multiple lineages and result in loss of recognition by epitope-specific T cells assessed by IFN-γ and cytotoxic killing assays. Complete loss of T cell responsiveness was seen due to Q213K in the A∗01:01-restricted CD8+ ORF3a epitope FTSDYYQLY207-215; due to P13L, P13S, and P13T in the B∗27:05-restricted CD8+ nucleocapsid epitope QRNAPRITF9-17; and due to T362I and P365S in the A∗03:01/A∗11:01-restricted CD8+ nucleocapsid epitope KTFPPTEPK361-369. CD8+ T cell lines unable to recognize variant epitopes have diverse T cell receptor repertoires. These data demonstrate the potential for T cell evasion and highlight the need for ongoing surveillance for variants capable of escaping T cell as well as humoral immunity.

Published
2021
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4. Recurrent emergence of SARS-CoV-2 spike deletion H69/V70 and its role in the Alpha variant B.1.1.7

Author

Bo Meng, Steven A. Kemp, Guido Papa, Rawlings Datir, Isabella A.T.M. Ferreira, Sara Marelli, William T. Harvey, Spyros Lytras, Ahmed Mohamed, Giulia Gallo, Nazia Thakur, Dami A. Collier, Petra Mlcochova, Lidia M. Duncan, Alessandro M. Carabelli, Julia C. Kenyon, Andrew M. Lever, Anna De Marco, Christian Saliba, Katja Culap, Elisabetta Cameroni, Nicholas J. Matheson, Luca Piccoli, Davide Corti, Leo C. James, David L. Robertson, Dalan Bailey, Ravindra K. Gupta, Samuel C. Robson, Nicholas J. Loman, Thomas R. Connor, Tanya Golubchik, Rocio T. Martinez Nunez, Catherine Ludden, Sally Corden, Ian Johnston, David Bonsall, Colin P. Smith, Ali R. Awan, Giselda Bucca, M. Estee Torok, Kordo Saeed, Jacqui A. Prieto, David K. Jackson, William L. Hamilton, Luke B. Snell, Catherine Moore, Ewan M. Harrison, Sonia Goncalves, Derek J. Fairley, Matthew W. Loose, Joanne Watkins, Rich Livett, Samuel Moses, Roberto Amato, Sam Nicholls, Matthew Bull, Darren L. Smith, Jeff Barrett, David M. Aanensen, Martin D. Curran, Surendra Parmar, Dinesh Aggarwal, James G. Shepherd, Matthew D. Parker, Sharon Glaysher, Matthew Bashton, Anthony P. Underwood, Nicole Pacchiarini, Katie F. Loveson, Kate E. Templeton, Cordelia F. Langford, John Sillitoe, Thushan I. de Silva, Dennis Wang, Dominic Kwiatkowski, Andrew Rambaut, Justin O’Grady, Simon Cottrell, Matthew T.G. Holden, Emma C. Thomson, Husam Osman, Monique Andersson, Anoop J. Chauhan, Mohammed O. Hassan-Ibrahim, Mara Lawniczak, Alex Alderton, Meera Chand, Chrystala Constantinidou, Meera Unnikrishnan, Alistair C. Darby, Julian A. Hiscox, Steve Paterson, Inigo Martincorena, Erik M. Volz, Andrew J. Page, Oliver G. Pybus, Andrew R. Bassett, Cristina V. Ariani, Michael H. Spencer Chapman, Kathy K. Li, Rajiv N. Shah, Natasha G. Jesudason, Yusri Taha, Martin P. McHugh, Rebecca Dewar, Aminu S. Jahun, Claire McMurray, Sarojini Pandey, James P. McKenna, Andrew Nelson, Gregory R. Young, Clare M. McCann, Scott Elliott, Hannah Lowe, Ben Temperton, Sunando Roy, Anna Price, Sara Rey, Matthew Wyles, Stefan Rooke, Sharif Shaaban, Mariateresa de Cesare, Laura Letchford, Siona Silveira, Emanuela Pelosi, Eleri Wilson-Davies, Myra Hosmillo, Áine O’Toole, Andrew R. Hesketh, Richard Stark, Louis du Plessis, Chris Ruis, Helen Adams, Yann Bourgeois, Stephen L. Michell, Dimitris Gramatopoulos, Jonathan Edgeworth, Judith Breuer, John A. Todd, Christophe Fraser, David Buck, Michaela John, Gemma L. Kay, Steve Palmer, Sharon J. Peacock, David Heyburn, Danni Weldon, Esther Robinson, Alan McNally, Peter Muir, Ian B. Vipond, John Boyes, Venkat Sivaprakasam, Tranprit Salluja, Samir Dervisevic, Emma J. Meader, Naomi R. Park, Karen Oliver, Aaron R. Jeffries, Sascha Ott, Ana da Silva Filipe, David A. Simpson, Chris Williams, Jane A.H. Masoli, Bridget A. Knight, Christopher R. Jones, Cherian Koshy, Amy Ash, Anna Casey, Andrew Bosworth, Liz Ratcliffe, Li Xu-McCrae, Hannah M. Pymont, Stephanie Hutchings, Lisa Berry, Katie Jones, Fenella Halstead, Thomas Davis, Christopher Holmes, Miren Iturriza-Gomara, Anita O. Lucaci, Paul Anthony Randell, Alison Cox, Pinglawathee Madona, Kathryn Ann Harris, Julianne Rose Brown, Tabitha W. Mahungu, Dianne Irish-Tavares, Tanzina Haque, Jennifer Hart, Eric Witele, Melisa Louise Fenton, Steven Liggett, Clive Graham, Emma Swindells, Jennifer Collins, Gary Eltringham, Sharon Campbell, Patrick C. McClure, Gemma Clark, Tim J. Sloan, Carl Jones, Jessica Lynch, Ben Warne, Steven Leonard, Jillian Durham, Thomas Williams, Sam T. Haldenby, Nathaniel Storey, Nabil-Fareed Alikhan, Nadine Holmes, Christopher Moore, Matthew Carlile, Malorie Perry, Noel Craine, Ronan A. Lyons, Angela H. Beckett, Salman Goudarzi, Christopher Fearn, Kate Cook, Hannah Dent, Hannah Paul, Robert Davies, Beth Blane, Sophia T. Girgis, Mathew A. Beale, Katherine L. Bellis, Matthew J. Dorman, Eleanor Drury, Leanne Kane, Sally Kay, Samantha McGuigan, Rachel Nelson, Liam Prestwood, Shavanthi Rajatileka, Rahul Batra, Rachel J. Williams, Mark Kristiansen, Angie Green, Anita Justice, Adhyana I.K. Mahanama, Buddhini Samaraweera, Nazreen F. Hadjirin, Joshua Quick, Radoslaw Poplawski, Leanne M. Kermack, Nicola Reynolds, Grant Hall, Yasmin Chaudhry, Malte L. Pinckert, Iliana Georgana, Robin J. Moll, Alicia Thornton, Richard Myers, Joanne Stockton, Charlotte A. Williams, Wen C. Yew, Alexander J. Trotter, Amy Trebes, George MacIntyre-Cockett, Alec Birchley, Alexander Adams, Amy Plimmer, Bree Gatica-Wilcox, Caoimhe McKerr, Ember Hilvers, Hannah Jones, Hibo Asad, Jason Coombes, Johnathan M. Evans, Laia Fina, Lauren Gilbert, Lee Graham, Michelle Cronin, Sara Kumziene-Summerhayes, Sarah Taylor, Sophie Jones, Danielle C. Groves, Peijun Zhang, Marta Gallis, Stavroula F. Louka, Igor Starinskij, Chris Jackson, Marina Gourtovaia, Gerry Tonkin-Hill, Kevin Lewis, Jaime M. Tovar-Corona, Keith James, Laura Baxter, Mohammad T. Alam, Richard J. Orton, Joseph Hughes, Sreenu Vattipally, Manon Ragonnet-Cronin, Fabricia F. Nascimento, David Jorgensen, Olivia Boyd, Lily Geidelberg, Alex E. Zarebski, Jayna Raghwani, Moritz U.G. Kraemer, Joel Southgate, Benjamin B. Lindsey, Timothy M. Freeman, Jon-Paul Keatley, Joshua B. Singer, Leonardo de Oliveira Martins, Corin A. Yeats, Khalil Abudahab, Ben E.W. Taylor, Mirko Menegazzo, John Danesh, Wendy Hogsden, Sahar Eldirdiri, Anita Kenyon, Jenifer Mason, Trevor I. Robinson, Alison Holmes, James Price, John A. Hartley, Tanya Curran, Alison E. Mather, Giri Shankar, Rachel Jones, Robin Howe, Sian Morgan, Elizabeth Wastenge, Michael R. Chapman, Siddharth Mookerjee, Rachael Stanley, Wendy Smith, Timothy Peto, David Eyre, Derrick Crook, Gabrielle Vernet, Christine Kitchen, Huw Gulliver, Ian Merrick, Martyn Guest, Robert Munn, Declan T. Bradley, Tim Wyatt, Charlotte Beaver, Luke Foulser, Sophie Palmer, Carol M. Churcher, Ellena Brooks, Kim S. Smith, Katerina Galai, Georgina M. McManus, Frances Bolt, Francesc Coll, Lizzie Meadows, Stephen W. Attwood, Alisha Davies, Elen De Lacy, Fatima Downing, Sue Edwards, Garry P. Scarlett, Sarah Jeremiah, Nikki Smith, Danielle Leek, Sushmita Sridhar, Sally Forrest, Claire Cormie, Harmeet K. Gill, Joana Dias, Ellen E. Higginson, Mailis Maes, Jamie Young, Michelle Wantoch, Dorota Jamrozy, Stephanie Lo, Minal Patel, Verity Hill, Claire M. Bewshea, Sian Ellard, Cressida Auckland, Ian Harrison, Chloe Bishop, Vicki Chalker, Alex Richter, Andrew Beggs, Angus Best, Benita Percival, Jeremy Mirza, Oliver Megram, Megan Mayhew, Liam Crawford, Fiona Ashcroft, Emma Moles-Garcia, Nicola Cumley, Richard Hopes, Patawee Asamaphan, Marc O. Niebel, Rory N. Gunson, Amanda Bradley, Alasdair Maclean, Guy Mollett, Rachel Blacow, Paul Bird, Thomas Helmer, Karlie Fallon, Julian Tang, Antony D. Hale, Louissa R. Macfarlane-Smith, Katherine L. Harper, Holli Carden, Nicholas W. Machin, Kathryn A. Jackson, Shazaad S.Y. Ahmad, Ryan P. George, Lance Turtle, Elaine O’Toole, Joanne Watts, Cassie Breen, Angela Cowell, Adela Alcolea-Medina, Themoula Charalampous, Amita Patel, Lisa J. Levett, Judith Heaney, Aileen Rowan, Graham P. Taylor, Divya Shah, Laura Atkinson, Jack C.D. Lee, Adam P. Westhorpe, Riaz Jannoo, Helen L. Lowe, Angeliki Karamani, Leah Ensell, Wendy Chatterton, Monika Pusok, Ashok Dadrah, Amanda Symmonds, Graciela Sluga, Zoltan Molnar, Paul Baker, Stephen Bonner, Sarah Essex, Edward Barton, Debra Padgett, Garren Scott, Jane Greenaway, Brendan A.I. Payne, Shirelle Burton-Fanning, Sheila Waugh, Veena Raviprakash, Nicola Sheriff, Victoria Blakey, Lesley-Anne Williams, Jonathan Moore, Susanne Stonehouse, Louise Smith, Rose K. Davidson, Luke Bedford, Lindsay Coupland, Victoria Wright, Joseph G. Chappell, Theocharis Tsoleridis, Jonathan Ball, Manjinder Khakh, Vicki M. Fleming, Michelle M. Lister, Hannah C. Howson-Wells, Louise Berry, Tim Boswell, Amelia Joseph, Iona Willingham, Nichola Duckworth, Sarah Walsh, Emma Wise, Nathan Moore, Matilde Mori, Nick Cortes, Stephen Kidd, Rebecca Williams, Laura Gifford, Kelly Bicknell, Sarah Wyllie, Allyson Lloyd, Robert Impey, Cassandra S. Malone, Benjamin J. Cogger, Nick Levene, Lynn Monaghan, Alexander J. Keeley, David G. Partridge, Mohammad Raza, Cariad Evans, Kate Johnson, Emma Betteridge, Ben W. Farr, Scott Goodwin, Michael A. Quail, Carol Scott, Lesley Shirley, Scott A.J. Thurston, Diana Rajan, Iraad F. Bronner, Louise Aigrain, Nicholas M. Redshaw, Stefanie V. Lensing, Shane McCarthy, Alex Makunin, Carlos E. Balcazar, Michael D. Gallagher, Kathleen A. Williamson, Thomas D. Stanton, Michelle L. Michelsen, Joanna Warwick-Dugdale, Robin Manley, Audrey Farbos, James W. Harrison, Christine M. Sambles, David J. Studholme, Angie Lackenby, Tamyo Mbisa, Steven Platt, Shahjahan Miah, David Bibby, Carmen Manso, Jonathan Hubb, Gavin Dabrera, Mary Ramsay, Daniel Bradshaw, Ulf Schaefer, Natalie Groves, Eileen Gallagher, David Lee, David Williams, Nicholas Ellaby, Hassan Hartman, Nikos Manesis, Vineet Patel, Juan Ledesma, Katherine A. Twohig, Elias Allara, Clare Pearson, Jeffrey K.J. Cheng, Hannah E. Bridgewater, Lucy R. Frost, Grace Taylor-Joyce, Paul E. Brown, Lily Tong, Alice Broos, Daniel Mair, Jenna Nichols, Stephen N. Carmichael, Katherine L. Smollett, Kyriaki Nomikou, Elihu Aranday-Cortes, Natasha Johnson, Seema Nickbakhsh, Edith E. Vamos, Margaret Hughes, Lucille Rainbow, Richard Eccles, Charlotte Nelson, Mark Whitehead, Richard Gregory, Matthew Gemmell, Claudia Wierzbicki, Hermione J. Webster, Chloe L. Fisher, Adrian W. Signell, Gilberto Betancor, Harry D. Wilson, Gaia Nebbia, Flavia Flaviani, Alberto C. Cerda, Tammy V. Merrill, Rebekah E. Wilson, Marius Cotic, Nadua Bayzid, Thomas Thompson, Erwan Acheson, Steven Rushton, Sarah O’Brien, David J. Baker, Steven Rudder, Alp Aydin, Fei Sang, Johnny Debebe, Sarah Francois, Tetyana I. Vasylyeva, Marina Escalera Zamudio, Bernardo Gutierrez, Angela Marchbank, Joshua Maksimovic, Karla Spellman, Kathryn McCluggage, Mari Morgan, Robert Beer, Safiah Afifi, Trudy Workman, William Fuller, Catherine Bresner, Adrienn Angyal, Luke R. Green, Paul J. Parsons, Rachel M. Tucker, Rebecca Brown, Max Whiteley, James Bonfield, Christoph Puethe, Andrew Whitwham, Jennifier Liddle, Will Rowe, Igor Siveroni, Thanh Le-Viet, Amy Gaskin, Rob Johnson, Irina Abnizova, Mozam Ali, Laura Allen, Ralph Anderson, Cristina Ariani, Siobhan Austin-Guest, Sendu Bala, Jeffrey Barrett, Andrew Bassett, Kristina Battleday, James Beal, Mathew Beale, Sam Bellany, Tristram Bellerby, Katie Bellis, Duncan Berger, Matt Berriman, Paul Bevan, Simon Binley, Jason Bishop, Kirsty Blackburn, Nick Boughton, Sam Bowker, Timothy Brendler-Spaeth, Iraad Bronner, Tanya Brooklyn, Sarah Kay Buddenborg, Robert Bush, Catarina Caetano, Alex Cagan, Nicola Carter, Joanna Cartwright, Tiago Carvalho Monteiro, Liz Chapman, Tracey-Jane Chillingworth, Peter Clapham, Richard Clark, Adrian Clarke, Catriona Clarke, Daryl Cole, Elizabeth Cook, Maria Coppola, Linda Cornell, Clare Cornwell, Craig Corton, Abby Crackett, Alison Cranage, Harriet Craven, Sarah Craw, Mark Crawford, Tim Cutts, Monika Dabrowska, Matt Davies, Joseph Dawson, Callum Day, Aiden Densem, Thomas Dibling, Cat Dockree, David Dodd, Sunil Dogga, Matthew Dorman, Gordon Dougan, Martin Dougherty, Alexander Dove, Lucy Drummond, Monika Dudek, Laura Durrant, Elizabeth Easthope, Sabine Eckert, Pete Ellis, Ben Farr, Michael Fenton, Marcella Ferrero, Neil Flack, Howerd Fordham, Grace Forsythe, Matt Francis, Audrey Fraser, Adam Freeman, Anastasia Galvin, Maria Garcia-Casado, Alex Gedny, Sophia Girgis, James Glover, Oliver Gould, Andy Gray, Emma Gray, Coline Griffiths, Yong Gu, Florence Guerin, Will Hamilton, Hannah Hanks, Ewan Harrison, Alexandria Harrott, Edward Harry, Julia Harvison, Paul Heath, Anastasia Hernandez-Koutoucheva, Rhiannon Hobbs, Dave Holland, Sarah Holmes, Gary Hornett, Nicholas Hough, Liz Huckle, Lena Hughes-Hallet, Adam Hunter, Stephen Inglis, Sameena Iqbal, Adam Jackson, David Jackson, Carlos Jimenez Verdejo, Matthew Jones, Kalyan Kallepally, Keely Kay, Jon Keatley, Alan Keith, Alison King, Lucy Kitchin, Matt Kleanthous, Martina Klimekova, Petra Korlevic, Ksenia Krasheninnkova, Greg Lane, Cordelia Langford, Adam Laverack, Katharine Law, Stefanie Lensing, Amanah Lewis-Wade, Jennifer Liddle, Quan Lin, Sarah Lindsay, Sally Linsdell, Rhona Long, Jamie Lovell, Jon Lovell, James Mack, Mark Maddison, Aleksei Makunin, Irfan Mamun, Jenny Mansfield, Neil Marriott, Matt Martin, Matthew Mayho, Jo McClintock, Sandra McHugh, Liz MapcMinn, Carl Meadows, Emily Mobley, Robin Moll, Maria Morra, Leanne Morrow, Kathryn Murie, Sian Nash, Claire Nathwani, Plamena Naydenova, Alexandra Neaverson, Ed Nerou, Jon Nicholson, Tabea Nimz, Guillaume G. Noell, Sarah O’Meara, Valeriu Ohan, Charles Olney, Doug Ormond, Agnes Oszlanczi, Yoke Fei Pang, Barbora Pardubska, Naomi Park, Aaron Parmar, Gaurang Patel, Maggie Payne, Sharon Peacock, Arabella Petersen, Deborah Plowman, Tom Preston, Michael Quail, Richard Rance, Suzannah Rawlings, Nicholas Redshaw, Joe Reynolds, Mark Reynolds, Simon Rice, Matt Richardson, Connor Roberts, Katrina Robinson, Melanie Robinson, David Robinson, Hazel Rogers, Eduardo Martin Rojo, Daljit Roopra, Mark Rose, Luke Rudd, Ramin Sadri, Nicholas Salmon, David Saul, Frank Schwach, Phil Seekings, Alison Simms, Matt Sinnott, Shanthi Sivadasan, Bart Siwek, Dale Sizer, Kenneth Skeldon, Jason Skelton, Joanna Slater-Tunstill, Lisa Sloper, Nathalie Smerdon, Chris Smith, Christen Smith, James Smith, Katie Smith, Michelle Smith, Sean Smith, Tina Smith, Leighton Sneade, Carmen Diaz Soria, Catarina Sousa, Emily Souster, Andrew Sparkes, Michael Spencer-Chapman, Janet Squares, Robert Stanley, Claire Steed, Tim Stickland, Ian Still, Mike Stratton, Michelle Strickland, Allen Swann, Agnieszka Swiatkowska, Neil Sycamore, Emma Swift, Edward Symons, Suzanne Szluha, Emma Taluy, Nunu Tao, Katy Taylor, Sam Taylor, Stacey Thompson, Mark Thompson, Mark Thomson, Nicholas Thomson, Scott Thurston, Dee Toombs, Benjamin Topping, Jaime Tovar-Corona, Daniel Ungureanu, James Uphill, Jana Urbanova, Philip Jansen Van, Valerie Vancollie, Paul Voak, Danielle Walker, Matthew Walker, Matt Waller, Gary Ward, Charlie Weatherhogg, Niki Webb, Alan Wells, Eloise Wells, Luke Westwood, Theo Whipp, Thomas Whiteley, Georgia Whitton, Sara Widaa, Mia Williams, Mark Wilson, and Sean Wright

Subjects
SARS-CoV-2, COVID-19, antibody escape, neutralizing antibodies, infectivity, spike mutation, Biology (General), QH301-705.5
Abstract

Summary: We report severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike ΔH69/V70 in multiple independent lineages, often occurring after acquisition of receptor binding motif replacements such as N439K and Y453F, known to increase binding affinity to the ACE2 receptor and confer antibody escape. In vitro, we show that, although ΔH69/V70 itself is not an antibody evasion mechanism, it increases infectivity associated with enhanced incorporation of cleaved spike into virions. ΔH69/V70 is able to partially rescue infectivity of spike proteins that have acquired N439K and Y453F escape mutations by increased spike incorporation. In addition, replacement of the H69 and V70 residues in the Alpha variant B.1.1.7 spike (where ΔH69/V70 occurs naturally) impairs spike incorporation and entry efficiency of the B.1.1.7 spike pseudotyped virus. Alpha variant B.1.1.7 spike mediates faster kinetics of cell-cell fusion than wild-type Wuhan-1 D614G, dependent on ΔH69/V70. Therefore, as ΔH69/V70 compensates for immune escape mutations that impair infectivity, continued surveillance for deletions with functional effects is warranted.

Published
2021
Full Text
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5. Changes in symptomatology, reinfection, and transmissibility associated with the SARS-CoV-2 variant B.1.1.7: an ecological study

Author

Mark S Graham, PhD, Carole H Sudre, PhD, Anna May, MA, Michela Antonelli, PhD, Benjamin Murray, MSc, Thomas Varsavsky, MSc, Kerstin Kläser, MSc, Liane S Canas, PhD, Erika Molteni, PhD, Marc Modat, PhD, David A Drew, PhD, Long H Nguyen, MD, Lorenzo Polidori, MSc, Somesh Selvachandran, MSc, Christina Hu, MA, Joan Capdevila, PhD, Alexander Hammers, ProfPhD, Andrew T Chan, ProfMD, Jonathan Wolf, MA, Tim D Spector, ProfPhD, Claire J Steves, PhD, Sebastien Ourselin, ProfPhD, Cherian Koshy, Amy Ash, Emma Wise, Nathan Moore, Matilde Mori, Nick Cortes, Jessica Lynch, Stephen Kidd, Derek J Fairley, Tanya Curran, James P McKenna, Helen Adams, Christophe Fraser, Tanya Golubchik, David Bonsall, Mohammed O Hassan-Ibrahim, Cassandra S Malone, Benjamin J Cogger, Michelle Wantoch, Nicola Reynolds, Ben Warne, Joshua Maksimovic, Karla Spellman, Kathryn McCluggage, Michaela John, Robert Beer, Safiah Afifi, Sian Morgan, Angela Marchbank, Anna Price, Christine Kitchen, Huw Gulliver, Ian Merrick, Joel Southgate, Martyn Guest, Robert Munn, Trudy Workman, Thomas R Connor, William Fuller, Catherine Bresner, Luke B Snell, Amita Patel, Themoula Charalampous, Gaia Nebbia, Rahul Batra, Jonathan Edgeworth, Samuel C Robson, Angela H Beckett, David M Aanensen, Anthony P Underwood, Corin A Yeats, Khalil Abudahab, Ben EW Taylor, Mirko Menegazzo, Gemma Clark, Wendy Smith, Manjinder Khakh, Vicki M Fleming, Michelle M Lister, Hannah C Howson-Wells, Louise Berry, Tim Boswell, Amelia Joseph, Iona Willingham, Carl Jones, Christopher Holmes, Paul Bird, Thomas Helmer, Karlie Fallon, Julian Tang, Veena Raviprakash, Sharon Campbell, Nicola Sheriff, Victoria Blakey, Lesley-Anne Williams, Matthew W Loose, Nadine Holmes, Christopher Moore, Matthew Carlile, Victoria Wright, Fei Sang, Johnny Debebe, Francesc Coll, Adrian W Signell, Gilberto Betancor, Harry D Wilson, Sahar Eldirdiri, Anita Kenyon, Thomas Davis, Oliver G Pybus, Louis du Plessis, Alex E Zarebski, Jayna Raghwani, Moritz UG Kraemer, Sarah Francois, Stephen W Attwood, Tetyana I Vasylyeva, Marina Escalera Zamudio, Bernardo Gutierrez, M. Estee Torok, William L Hamilton, Ian G Goodfellow, Grant Hall, Aminu S Jahun, Yasmin Chaudhry, Myra Hosmillo, Malte L Pinckert, Iliana Georgana, Samuel Moses, Hannah Lowe, Luke Bedford, Jonathan Moore, Susanne Stonehouse, Chloe L Fisher, Ali R Awan, John BoYes, Judith Breuer, Kathryn Ann Harris, Julianne Rose Brown, Divya Shah, Laura Atkinson, Jack CD Lee, Nathaniel Storey, Flavia Flaviani, Adela Alcolea-Medina, Rebecca Williams, Gabrielle Vernet, Michael R Chapman, Lisa J Levett, Judith Heaney, Wendy Chatterton, Monika Pusok, Li Xu-McCrae, Darren L Smith, Matthew Bashton, Gregory R Young, Alison Holmes, Paul Anthony Randell, Alison Cox, Pinglawathee Madona, Frances Bolt, James Price, Siddharth Mookerjee, Manon Ragonnet-Cronin, Fabricia F. Nascimento, David Jorgensen, Igor Siveroni, Rob Johnson, Olivia Boyd, Lily Geidelberg, Erik M Volz, Aileen Rowan, Graham P Taylor, Katherine L Smollett, Nicholas J Loman, Joshua Quick, Claire McMurray, Joanne Stockton, Sam Nicholls, Will Rowe, Radoslaw Poplawski, Alan McNally, Rocio T Martinez Nunez, Jenifer Mason, Trevor I Robinson, Elaine O'Toole, Joanne Watts, Cassie Breen, Angela Cowell, Graciela Sluga, Nicholas W Machin, Shazaad S Y Ahmad, Ryan P George, Fenella Halstead, Venkat Sivaprakasam, Wendy Hogsden, Chris J Illingworth, Chris Jackson, Emma C Thomson, James G Shepherd, Patawee Asamaphan, Marc O Niebel, Kathy K Li, Rajiv N Shah, Natasha G Jesudason, Lily Tong, Alice Broos, Daniel Mair, Jenna Nichols, Stephen N Carmichael, Kyriaki Nomikou, Elihu Aranday-Cortes, Natasha Johnson, Igor Starinskij, Ana da Silva Filipe, David L Robertson, Richard J Orton, Joseph Hughes, Sreenu Vattipally, Joshua B Singer, Seema Nickbakhsh, Antony D Hale, Louissa R Macfarlane-Smith, Katherine L Harper, Holli Carden, Yusri Taha, Brendan AI Payne, Shirelle Burton-Fanning, Sheila Waugh, Jennifer Collins, Gary Eltringham, Steven Rushton, Sarah O'Brien, Amanda Bradley, Alasdair Maclean, Guy Mollett, Rachel Blacow, Kate E Templeton, Martin P McHugh, Rebecca Dewar, Elizabeth Wastenge, Samir Dervisevic, Rachael Stanley, Emma J Meader, Lindsay Coupland, Louise Smith, Clive Graham, Edward Barton, Debra Padgett, Garren Scott, Emma Swindells, Jane Greenaway, Andrew Nelson, Clare M McCann, Wen C Yew, Monique Andersson, Timothy Peto, Anita Justice, David Eyre, Derrick Crook, Tim J Sloan, Nichola Duckworth, Sarah Walsh, Anoop J Chauhan, Sharon Glaysher, Kelly Bicknell, Sarah Wyllie, Scott Elliott, Allyson Lloyd, Robert Impey, Nick Levene, Lynn Monaghan, Declan T Bradley, Tim Wyatt, Elias Allara, Clare Pearson, Husam Osman, Andrew Bosworth, Esther Robinson, Peter Muir, Ian B Vipond, Richard Hopes, Hannah M Pymont, Stephanie Hutchings, Martin D Curran, Surendra Parmar, Angie Lackenby, Tamyo Mbisa, Steven Platt, Shahjahan Miah, David Bibby, Carmen Manso, Jonathan Hubb, Meera Chand, Gavin Dabrera, Mary Ramsay, Daniel Bradshaw, Alicia Thornton, Richard Myers, Ulf Schaefer, Natalie Groves, Eileen Gallagher, David Lee, David Williams, Nicholas Ellaby, Ian Harrison, Hassan Hartman, Nikos Manesis, Vineet Patel, Chloe Bishop, Vicki Chalker, Juan Ledesma, Katherine A Twohig, 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 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, Alison E Mather, David J Baker, Steven Rudder, Alp Aydin, Gemma L Kay, Alexander J Trotter, Nabil-Fareed Alikhan, Leonardo de Oliveira Martins, Thanh Le-Viet, Lizzie Meadows, Anna Casey, Liz Ratcliffe, David A Simpson, Zoltan Molnar, Thomas Thompson, Erwan Acheson, Jane AH Masoli, Bridget A Knight, Sian Ellard, Cressida Auckland, Christopher R Jones, Tabitha W Mahungu, Dianne Irish-Tavares, Tanzina Haque, Jennifer Hart, Eric Witele, Melisa Louise Fenton, Ashok Dadrah, Amanda Symmonds, Tranprit Saluja, Yann Bourgeois, Garry P Scarlett, Katie F Loveson, Salman Goudarzi, Christopher Fearn, Kate Cook, Hannah Dent, Hannah Paul, David G Partridge, Mohammad Raza, Cariad Evans, Kate Johnson, Steven Liggett, Paul Baker, Stephen Bonner, Sarah Essex, Ronan A Lyons, Kordo Saeed, Adhyana I.K Mahanama, Buddhini Samaraweera, Siona Silveira, Emanuela Pelosi, Eleri Wilson-Davies, Rachel J Williams, Mark Kristiansen, Sunando Roy, Charlotte A Williams, Marius Cotic, Nadua Bayzid, Adam P Westhorpe, John A Hartley, Riaz Jannoo, Helen L Lowe, Angeliki Karamani, Leah Ensell, Jacqui A Prieto, Sarah Jeremiah, Dimitris Grammatopoulos, Sarojini Pandey, Lisa Berry, Katie Jones, Alex Richter, Andrew Beggs, Angus Best, Benita Percival, Jeremy Mirza, Oliver Megram, Megan Mayhew, Liam Crawford, Fiona Ashcroft, Emma Moles-Garcia, Nicola Cumley, Colin P Smith, Giselda Bucca, Andrew R Hesketh, Beth Blane, Sophia T Girgis, Danielle Leek, Sushmita Sridhar, Sally Forrest, Claire Cormie, Harmeet K Gill, Joana Dias, Ellen E Higginson, Mailis Maes, Jamie Young, Leanne M Kermack, Ravi Kumar Gupta, Catherine Ludden, Sharon J Peacock, Sophie Palmer, Carol M Churcher, Nazreen F Hadjirin, Alessandro M Carabelli, Ellena Brooks, Kim S Smith, Katerina Galai, Georgina M McManus, Chris Ruis, Rose K Davidson, Andrew Rambaut, Thomas Williams, Carlos E Balcazar, Michael D Gallagher, Áine O'Toole, Stefan Rooke, Verity Hill, Kathleen A Williamson, Thomas D Stanton, Stephen L Michell, Claire M Bewshea, Ben Temperton, Michelle L Michelsen, Joanna Warwick-Dugdale, Robin Manley, Audrey Farbos, James W Harrison, Christine M Sambles, David J Studholme, Aaron R Jeffries, Alistair C Darby, Julian A Hiscox, Steve Paterson, Miren Iturriza-Gomara, Kathryn A Jackson, Anita O Lucaci, Edith E Vamos, Margaret Hughes, Lucille Rainbow, Richard Eccles, Charlotte Nelson, Mark Whitehead, Lance Turtle, Sam T Haldenby, Richard Gregory, Matthew Gemmell, Claudia Wierzbicki, Hermione J Webster, Thushan I de Silva, Nikki 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 M Tucker, Rebecca Brown, Matthew Wyles, Max Whiteley, Peijun Zhang, Marta Gallis, Stavroula F Louka, Chrystala Constantinidou, Meera Unnikrishnan, Sascha Ott, Jeffrey K.J. Cheng, Hannah E. Bridgewater, Lucy R. Frost, Grace Taylor-Joyce, Richard Stark, Laura Baxter, Mohammad T. Alam, Paul E Brown, Dinesh Aggarwal, Alberto C Cerda, Tammy V Merrill, Rebekah E Wilson, Patrick C McClure, Joseph G Chappell, Theocharis Tsoleridis, Jonathan Ball, David Buck, John A Todd, Angie Green, Amy Trebes, George MacIntyre-Cockett, Mariateresa de Cesare, Alex Alderton, Roberto Amato, Cristina V Ariani, Mathew A Beale, Charlotte Beaver, Katherine L Bellis, Emma Betteridge, James Bonfield, John Danesh, Matthew J Dorman, Eleanor Drury, Ben W Farr, Luke Foulser, Sonia Goncalves, Scott Goodwin, Marina Gourtovaia, Ewan M Harrison, David K Jackson, Dorota Jamrozy, Ian Johnston, Leanne Kane, Sally Kay, Jon-Paul Keatley, Dominic Kwiatkowski, Cordelia F Langford, Mara Lawniczak, Laura Letchford, Rich Livett, Stephanie Lo, Inigo Martincorena, Samantha McGuigan, Rachel Nelson, Steve Palmer, Naomi R Park, Minal Patel, Liam Prestwood, Christoph Puethe, Michael A Quail, Shavanthi Rajatileka, Carol Scott, Lesley Shirley, John Sillitoe, Michael H Spencer Chapman, Scott AJ Thurston, Gerry Tonkin-Hill, Danni Weldon, Diana Rajan, Iraad F Bronner, Louise Aigrain, Nicholas M Redshaw, Stefanie V Lensing, Robert Davies, Andrew Whitwham, Jennifier Liddle, Kevin Lewis, Jaime M Tovar-Corona, Steven Leonard, Jillian Durham, Andrew R Bassett, Shane McCarthy, Robin J Moll, Keith James, Karen Oliver, Alex Makunin, Jeff Barrett, and Rory N Gunson

Subjects
Public aspects of medicine, RA1-1270
Abstract

Summary: Background: The SARS-CoV-2 variant B.1.1.7 was first identified in December, 2020, in England. We aimed to investigate whether increases in the proportion of infections with this variant are associated with differences in symptoms or disease course, reinfection rates, or transmissibility. Methods: We did an ecological study to examine the association between the regional proportion of infections with the SARS-CoV-2 B.1.1.7 variant and reported symptoms, disease course, rates of reinfection, and transmissibility. Data on types and duration of symptoms were obtained from longitudinal reports from users of the COVID Symptom Study app who reported a positive test for COVID-19 between Sept 28 and Dec 27, 2020 (during which the prevalence of B.1.1.7 increased most notably in parts of the UK). From this dataset, we also estimated the frequency of possible reinfection, defined as the presence of two reported positive tests separated by more than 90 days with a period of reporting no symptoms for more than 7 days before the second positive test. The proportion of SARS-CoV-2 infections with the B.1.1.7 variant across the UK was estimated with use of genomic data from the COVID-19 Genomics UK Consortium and data from Public Health England on spike-gene target failure (a non-specific indicator of the B.1.1.7 variant) in community cases in England. We used linear regression to examine the association between reported symptoms and proportion of B.1.1.7. We assessed the Spearman correlation between the proportion of B.1.1.7 cases and number of reinfections over time, and between the number of positive tests and reinfections. We estimated incidence for B.1.1.7 and previous variants, and compared the effective reproduction number, Rt, for the two incidence estimates. Findings: From Sept 28 to Dec 27, 2020, positive COVID-19 tests were reported by 36 920 COVID Symptom Study app users whose region was known and who reported as healthy on app sign-up. We found no changes in reported symptoms or disease duration associated with B.1.1.7. For the same period, possible reinfections were identified in 249 (0·7% [95% CI 0·6–0·8]) of 36 509 app users who reported a positive swab test before Oct 1, 2020, but there was no evidence that the frequency of reinfections was higher for the B.1.1.7 variant than for pre-existing variants. Reinfection occurrences were more positively correlated with the overall regional rise in cases (Spearman correlation 0·56–0·69 for South East, London, and East of England) than with the regional increase in the proportion of infections with the B.1.1.7 variant (Spearman correlation 0·38–0·56 in the same regions), suggesting B.1.1.7 does not substantially alter the risk of reinfection. We found a multiplicative increase in the Rt of B.1.1.7 by a factor of 1·35 (95% CI 1·02–1·69) relative to pre-existing variants. However, Rt fell below 1 during regional and national lockdowns, even in regions with high proportions of infections with the B.1.1.7 variant. Interpretation: The lack of change in symptoms identified in this study indicates that existing testing and surveillance infrastructure do not need to change specifically for the B.1.1.7 variant. In addition, given that there was no apparent increase in the reinfection rate, vaccines are likely to remain effective against the B.1.1.7 variant. Funding: Zoe Global, Department of Health (UK), Wellcome Trust, Engineering and Physical Sciences Research Council (UK), National Institute for Health Research (UK), Medical Research Council (UK), Alzheimer's Society.

Published
2021
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6. Hospital admission and emergency care attendance risk for SARS-CoV-2 delta (B.1.617.2) compared with alpha (B.1.1.7) variants of concern: a cohort study

Author

Harry D Wilson, Elaine O'Toole, Andrew Bassett, Moritz U. G. Kraemer, Beth Blane, Scott Goodwin, Giri Shankar, Joseph Hughes, Lucy R. Frost, Alicia Thornton, Scott Elliott, Tammy V Merrill, Sheila Waugh, Alexander Adams, Peter Muir, Graciela Sluga, Rebecca Williams, Hannah Dent, Christophe Fraser, Shavanthi Rajatileka, John C. Hartley, Luke B Snell, Benjamin J Cogger, Lance Turtle, Alex Makunin, John A. Todd, Victoria Wright, Daniela De Angelis, James McKenna, Dinesh Aggarwal, Jonathan K. Ball, Jillian Durham, Garren Scott, Thushan I de Silva, Veena Raviprakash, Hannah M Pymont, Jason Coombes, Anita Lucaci, Luke R. Green, Leigh M Jackson, Hermione J. Webster, Louis du Plessis, David A. Jackson, Minal Patel, Áine O'Toole, Ravi Gupta, Marc Niebel, Garry Scarlett, Rajiv Shah, Guy Mollett, Kathy Li, Rory Gunson, Matthew Bashton, Carl Jones, Sara Kumziene-Summerhayes, Zoltan Molnar, Siona Silveira, Malte L Pinckert, Catherine Ludden, Angeliki Karamani, Leanne Kane, Brendan A I Payne, Alan McNally, Clare M. McCann, Holli Carden, Mohammad Raza, Alison E. Mather, Kate B. Cook, Amy Gaskin, David J. Williams, Shaun R. Seaman, Christopher I. Jones, Gilberto Betancor, Matthew T. G. Holden, Jennifier Liddle, Meera Unnikrishnan, Angie Green, Ben Taylor, Kelly Bicknell, Alexander J. Trotter, Emma Meader, Leanne M Kermack, Nathaniel Storey, Michelle Cronin, Sally Forrest, Sarah Jeremiah, Asad Zaidi, M Morgan, Alasdair MacLean, Thomas R. Connor, Johnathan M Evans, Rachael Stanley, Ryan P George, Nadine Holmes, Richard H. Myers, Christine Sambles, Bernardo Gutierrez, Jeffrey K. J. Cheng, Tim Wyatt, Natasha Jesudason, Lindsay Coupland, Monika Pusok, Manon Ragonnet-Cronin, Jenifer Mason, Joshua Maksimovic, Russell Hope, Alison Holmes, David Simpson, Radoslaw Poplawski, Amelia Joseph, Erwan Acheson, James Bonfield, Mara K. N. Lawniczak, Sascha Ott, Lesley-Anne Williams, Jessica Lynch, Graham P. Taylor, Anita Kenyon, Elizabeth Wastenge, Megan Mayhew, Adhyana I K Mahanama, Stavroula F Louka, Chloe Bishop, Esther Robinson, Darren Smith, Anne M. Presanis, Matthew Carlile, Thomas D Stanton, Dennis Wang, Katerina Galai, Adam P Westhorpe, Flavia Flaviani, Michelle Wantoch, Max Whiteley, Yann Bourgeois, Matthew Gemmell, Mary Ramsay, A Lloyd, Simon Thelwall, Hannah C. Howson-Wells, Joseph G. Chappell, Steve Paterson, Gary Eltringham, Robert Impey, Siddharth Mookerjee, Steven Platt, Emma Swindells, Laura Letchford, Alex Alderton, Lee Graham, Safiah Afifi, David C. Lee, Cassie Breen, Melisa Louise Fenton, Benita Percival, Adrian W Signell, Tanya Golubchik, Ian B Vipond, Eleri Wilson-Davies, Angie Lackenby, Laura Atkinson, Sarojini Pandey, Nazreen F. Hadjirin, Michael A Chapman, Huw Gulliver, Joana Dias, Grant Hall, Antony D Hale, Hassan Hartman, Alp Aydin, Louise Smith, Ashok Dadrah, Johnny Debebe, Sarah Walsh, Stephanie W. Lo, Andrew Bosworth, Bridget Knight, Hannah E Bridgewater, Nadua Bayzid, Gemma L. Kay, Richard Gregory, Sally Kay, Ellena Brooks, Andre Charlett, Georgina M McManus, Riaz Jannoo, Victoria Blakey, Carol Scott, Rachel Nelson, Liz Ratcliffe, Gerry Tonkin-Hill, Verity Hill, Joanne D. Stockton, Danielle Leek, Steven Leonard, Stephanie Hutchings, Jonathan D. Moore, Kathryn Ann Harris, Sophie Jones, Venkat Sivaprakasam, Amy Plimmer, Tanzina Haque, Katherine L. Bellis, Khalil Abudahab, Dianne Irish-Tavares, Gaia Nebbia, Kathryn A Jackson, Stephen W Attwood, Daniel Mair, Sreenu Vattipally, Susanne Stonehouse, Ian Merrick, Lucille Rainbow, Mathew A. Beale, Angela Helen Beckett, Ember Hilvers, Thomas Helmer, Jenna Nichols, Giselda Bucca, Salman Goudarzi, Christopher Ruis, Surendra Parmar, Angela Cowell, Alberto C Cerda, Divya K. Shah, Judith Heaney, E. Thomson, Kyriaki Nomikou, Nicole Pacchiarini, Katherine L Harper, Fatima Downing, M. Estée Török, Michelle L Michelsen, Aaron R. Jeffries, Jennifer Collins, Christopher Williams, Katie F. Loveson, Steven Rudder, Theocharis Tsoleridis, Robert Davies, David Robertson, Katherine Smollett, Kathryn McCluggage, Liam Crawford, Inigo Martincorena, Charlotte Beaver, Oliver Megram, Karla Spellman, Sam Haldenby, Emma Betteridge, William D. Fuller, Will P. M. Rowe, Cherian Koshy, Tim E. A. Peto, Alison Cox, Natasha Johnson, Tanya Curran, Sharif Shaaban, Tamyo Mbisa, Cordelia Langford, Eric Witele, Andrew J. Page, Christoph Puethe, Nicola Reynolds, Paul W Bird, Louise Aigrain, Ronan Lyons, Amy Trebes, Sally Corden, Steven Rushton, Jack Cd Lee, Jane Greenaway, Hibo Asad, Amanda Bradley, Mohammed O Hassan-Ibrahim, Shane McCarthy, Fei Sang, Matthew Loose, Hannah Jones, Keith D. James, Chloe L Fisher, Chrystala Constantinidou, Alex G. Richter, Jane A. H. Masoli, Michael Gallagher, Vicki M. Fleming, Anna Price, Amy Ash, Michaela John, Alex Zarebski, Fenella D. Halstead, John Danesh, Christine Kitchen, Aminu S Jahun, Mark Whitehead, Julianne R Brown, Catherine Bresner, Marius Cotic, Stefanie V Lensing, Nick Levene, Louissa R Macfarlane-Smith, Wendy Hogsden, Cressida Auckland, Eleanor Drury, Richard Eccles, Jennifer Hart, Seema Nickbakhsh, Alisha Davies, David M. Aanensen, Shirelle Burton-Fanning, Ben Farr, Buddhini Samaraweera, Sarah Wyllie, Hannah Lowe, Richard J. Orton, Martin D. Curran, Carol Churcher, Karen Oliver, Elihu Aranday-Cortes, Wen Yew, Thanh Le-Viet, Matthew Parker, Katherine A Twohig, Shahjahan Miah, Samuel M. Nicholls, G MacIntyre-Cockett, Tranprit Saluja, Charlotte Nelson, Vicki Chalker, Roberto Amato, Ellen Higginson, Timothy M. Freeman, Christopher W Holmes, Yasmin Chaudhry, Elias Allara, Alec Birchley, Iraad Bronner, Emma Moles-Garcia, Angus I. Best, Anna L. Casey, Audrey Farbos, Nicholas W Machin, David W Eyre, Tim Boswell, Charlotte A Williams, Elen De Lacy, Matthew J. Bull, Matilde Mori, Carmen F. Manso, Peijun Zhang, Sahar Eldirdiri, Dimitris Grammatopoulos, Corin Yeats, Claudia Wierzbicki, David G Partridge, Kordo Saeed, Nichola Duckworth, David J. Studholme, Harmeet K Gill, Juan Ledesma, Thomas R. A. Davis, Sushmita Sridhar, Clive Graham, Husam Osman, Julian A. Hiscox, Helen Adams, Christopher Fearn, Fabrícia F. Nascimento, Ulf Schaefer, James W. Harrison, Andrew J. Nelson, Joshua Quick, Mohammad Tauqeer Alam, Liam Prestwood, Nikos Manesis, Julian Tang, Justin O'Grady, Sophia T Girgis, Louise Berry, Gemma Clark, Marina Escalera Zamudio, Karlie Fallon, Tim J Sloan, Joanne Watkins, Clare Pearson, Andrew D Beggs, Rachel Williams, Luke Bedford, Trevor Robinson, Nicholas M Redshaw, Richard Hopes, Mirko Menegazzo, Katherine Twohig, Gabrielle Vernet, Steven Liggett, Mariateresa de Cesare, Derrick W. Crook, Dominic P. Kwiatkowski, Mark Kristiansen, Miren Iturriza-Gomara, Christopher I. Moore, Claire Cormie, Olivia Boyd, Nikki Smith, Noel Craine, Kathleen A. Williamson, John Boyes, Sian Ellard, Cristina V. Ariani, Wendy Chatterton, David Bonsall, Kevin Lewis, David Jorgensen, Ian Harrison, Christopher Jackson, Martin P McHugh, Danni Weldon, Michael A. Quail, Amita Patel, Lily Geidelberg, Myra Hosmillo, Judith Breuer, Cariad Evans, Edward Barton, Trudy Workman, Derek Fairley, Vineet Patel, Daniel Bradshaw, Robin Manley, Scott Aj Thurston, John Sillitoe, Monique Andersson, Sharon J. Peacock, Jamie Lopez-Bernal, Thomas Thompson, Nabil-Fareed Alikhan, Ben Temperton, Paul Baker, Robin J Moll, Laura Gifford, Nicholas J. Loman, Jayna Raghwani, Jacqui Prieto, Andrew Hesketh, Oliver G. Pybus, Adela Alcolea-Medina, David Buck, Gregory R Young, Alistair C. Darby, Sónia Gonçalves, Aileen G. Rowan, Tabitha Mahungu, Nicholas Ellaby, Jon-Paul Keatley, Lily Tong, Robert Beer, Martyn Guest, Lisa J Levett, Ali R Awan, Iliana Georgana, Paul E Brown, Li Xu-McCrae, Stephen P. Kidd, Sara Rey, Shazaad Ahmad, Danielle C. Groves, Tetyana I. Vasylyeva, David F. Bibby, Nathan Moore, Fiona Ashcroft, Igor Starinskij, Hannah Paul, Claire McMurray, Michael Spencer Chapman, Carlos Balcazar, Joanna Warwick-Dugdale, Pinglawathee Madona, Edith Vamos, Lesley Shirley, Kate Templeton, Luke Foulser, Igor Siveroni, Ewan M. Harrison, Sian Morgan, Diana Rajan, S Taylor, Laia Fina, Naomi Park, Sarah J. O'Brien, Alessandro M Carabelli, Angela Marchbank, Sunando Roy, Leonardo de Oliveira Martins, Steve Palmer, Jonathan Hubb, Alexander J Keeley, Francesc Coll, Malorie Perry, Paul J. Parsons, Anthony Underwood, Patawee Asamaphan, William L Hamilton, Tommy Nyberg, Sophie Palmer, Amanda Symmonds, Anoop Chauhan, Robert Johnson, Christopher J. R. Illingworth, James Shepherd, Wendy Smith, Rich Livett, Rachel Blacow, Margaret Hughes, Jeremy Mirza, Joanne Watts, Jonathan D. Edgeworth, Sarah François, Sue Edwards, Adrienn Angyal, Thomas N. Williams, Marta Gallis, Lauren Gilbert, Paul Randell, Kate Johnson, Eileen Gallagher, Nick Cortes, Yusri Taha, Leah Ensell, Emanuela Pelosi, Stefan Rooke, Michelle Lister, Ana da Silva Filipe, Cassandra S Malone, Themoula Charalampous, Benjamin B Lindsey, Natalie Groves, Colin Smith, Ross J Harris, Rebekah E Wilson, Stephen Bonner, Richard Stark, Sharon Campbell, Nicola Sheriff, Helen L Lowe, Rachel Jones, Ben Warne, Rose K Davidson, Declan Bradley, Ian Johnston, Jeffrey C. Barrett, Joshua B Singer, Shirin Aliabadi, Andrew Whitwham, Patrick McClure, Samuel Robson, Sharon Glaysher, Robert J. Munn, Emma L. Wise, Laura Baxter, Kim S Smith, Catherine Moore, Bree Gatica-Wilcox, Alice Broos, Sarah Essex, David Baker, Manjinder Khakh, Dorota Jamrozy, Rachel Tucker, Ian Goodfellow, S.E. Moses, Nicola Cumley, Robin Howe, Meera Chand, James I. Price, Marina Gourtovaia, Debra Padgett, Jaime Tovar-Corona, Stephen L. Michell, Matthew J. Dorman, Lizzie Meadows, David Heyburn, Iona Willingham, Rocio Martinez Nunez, Grace Taylor-Joyce, Claire M Bewshea, Anita Justice, Simon Cottrell, Rebecca C H Brown, Jamie Young, Gavin Dabrera, Matthew Wyles, Stephen Carmichael, Lisa Berry, Frances Bolt, Andrew Rambaut, Samir Dervisevic, Erik M. Volz, Rahul Batra, Caoimhe McKerr, Samantha McGuigan, Katie Jones, Mailis Maes, Rebecca Dewar, Mary Sinnathamby, Joel Southgate, and Lynn Monaghan

Subjects
medicine.medical_specialty, business.industry, Proportional hazards model, Public health, Hazard ratio, Attendance, C500, Vaccination, Infectious Diseases, Relative risk, Internal medicine, Cohort, medicine, business, Cohort study
Abstract

Background: \ud The SARS-CoV-2 delta (B.1.617.2) variant was first detected in England in March, 2021. It has since rapidly become the predominant lineage, owing to high transmissibility. It is suspected that the delta variant is associated with more severe disease than the previously dominant alpha (B.1.1.7) variant. We aimed to characterise the severity of the delta variant compared with the alpha variant by determining the relative risk of hospital attendance outcomes.\ud \ud Methods: \ud This cohort study was done among all patients with COVID-19 in England between March 29 and May 23, 2021, who were identified as being infected with either the alpha or delta SARS-CoV-2 variant through whole-genome sequencing. Individual-level data on these patients were linked to routine health-care datasets on vaccination, emergency care attendance, hospital admission, and mortality (data from Public Health England's Second Generation Surveillance System and COVID-19-associated deaths dataset; the National Immunisation Management System; and NHS Digital Secondary Uses Services and Emergency Care Data Set). The risk for hospital admission and emergency care attendance were compared between patients with sequencing-confirmed delta and alpha variants for the whole cohort and by vaccination status subgroups. Stratified Cox regression was used to adjust for age, sex, ethnicity, deprivation, recent international travel, area of residence, calendar week, and vaccination status.\ud \ud Findings: \ud Individual-level data on 43 338 COVID-19-positive patients (8682 with the delta variant, 34 656 with the alpha variant; median age 31 years [IQR 17–43]) were included in our analysis. 196 (2·3%) patients with the delta variant versus 764 (2·2%) patients with the alpha variant were admitted to hospital within 14 days after the specimen was taken (adjusted hazard ratio [HR] 2·26 [95% CI 1·32–3·89]). 498 (5·7%) patients with the delta variant versus 1448 (4·2%) patients with the alpha variant were admitted to hospital or attended emergency care within 14 days (adjusted HR 1·45 [1·08–1·95]). Most patients were unvaccinated (32 078 [74·0%] across both groups). The HRs for vaccinated patients with the delta variant versus the alpha variant (adjusted HR for hospital admission 1·94 [95% CI 0·47–8·05] and for hospital admission or emergency care attendance 1·58 [0·69–3·61]) were similar to the HRs for unvaccinated patients (2·32 [1·29–4·16] and 1·43 [1·04–1·97]; p=0·82 for both) but the precision for the vaccinated subgroup was low.\ud \ud Interpretation: \ud This large national study found a higher hospital admission or emergency care attendance risk for patients with COVID-19 infected with the delta variant compared with the alpha variant. Results suggest that outbreaks of the delta variant in unvaccinated populations might lead to a greater burden on health-care services than the alpha variant.\ud \ud Funding: \ud Medical Research Council; UK Research and Innovation; Department of Health and Social Care; and National Institute for Health Research.

Published
2022

7. COVID-19 vaccine coverage in health-care workers in England and effectiveness of BNT162b2 mRNA vaccine against infection (SIREN): a prospective, multicentre, cohort study

Author

Amanda Semper, P Burns, K Gajee, Amoolya Vusirikala, L Moore, S Joyce, Paul Klenerman, R Longfellow, R Matthews, Jacqueline Hewson, L Prentice, Alastair Grant, Edgar Wellington, A Tengbe, S Ambalkar, Alex Soriano, I Karagiannis, A Ashby, C Carr, O Kay, B Larru, Manjula Meda, T Lewis, H Aziz, R Chaudhuri, Ioannis Karagiannis, Martin S. Williams, J Conneely, Tim Planche, A M Moody, A Ho, Ashley Otter, K McLelland-Brooks, N Todd, J Alderton, Matthew T. G. Holden, A Boulos, T DeSilva, A Rajgopal, R Pritchard Jones, J Khawam, SC Bain, V J Hall, S Birch, Sarah Foulkes, MA Chand, CS Brown, P Cowling, K Hollinshead, M Halkes, M Ramsay, Cathy Rowe, Colin S Brown, Mark Joseph, N Slawson, Blanche Oguti, L Hall, J Russell, Ayoub Saei, Linda Partridge, Shahjahan Miah, L Coke, Steven Platt, Angie Lackenby, Victoria Hall, M Sartaj, L Keen, A Saei, T Chin, C Thomas, Louise Robinson, Christopher W Holmes, C Subudhi, M Beekes, R Laugharne, Diane Wycherley, R.J. Shorten, R Temple-Purcell, H Chenoweth, V Maxwell, A Atti, Padmasayee Papineni, J Giles, K. Black, M Booth, Jane Democratis, D McCracken, L Cromey, Peter Kirwan, D Delgado, D Hilton, R Crosby-Nwaobi, Susanna Dunachie, A Roebuck, G Sebbage, S Foulkes, K Tempeton, Edward M. Smith, J Murira, Ajay Chawla, Joanna Ellis, J Lopez-Bernal, S Jose, Nick Andrews, A Charlett, Bjl Burton, I Sinanovic, N Aldridge, Katie Jeffery, Gretchen A Stevens, Y Ellis, J Powell, Shân Davies, Alan Jackson, Jonathan L. Heeney, A Dave, B Oguti, A Swan, EA Sheridan, Sara Bennett, Susan Hopkins, T Donaghy, Sakib Rokadiya, Jasmin Islam, S Akhtar, J Mouland, P Domingos, J Harwood, Christian Gabriel, Christopher J A Duncan, Stephen R. Williams, S Hams, E Cameron, F Westwell, Keith D. James, Meaghan Kall, K Pagget, Justin Pepperell, Robert Tilley, A O'Kelly, S Horne, K Potts, S Gormley, F Sanderson, Sharen Painter, S. Stone, Mariyam Mirfenderesky, Tabitha Mahungu, S Baillon, R Kyffin, S Organ, S Brake, Andre Charlett, S Brand, D Browne, J Ledger, Meera Chand, Madhumita Shrotri, Michael J. Cole, Debra Padgett, M Lee, Martin Wiselka, A M O'Connell, Minal Patel, Katie Munro, L Haahr, T M Byrne, J Gunn, Naomi F. Walker, P Bakker, P Cieciwa, Stephen Winchester, N Chitalia, B Wadams, Michael P. Murphy, P Staves, Ken Agwuh, Cressida Auckland, Sarah Meisner, Ejm Monk, J Howard, C Duff, Susan R. Hopkins, N Andrews, J Elliott, K Braithwaite, AJ Plant, M Howard, Sharon Campbell, A Nissr, Stuart K. Roberts, D Pople, G Maloney, L Mabey, T Bailey, Simon Warren, S Orr, Alex Horsley, J Radmore, Lance Turtle, Helen V. Smith, Badrinathan Chandrasekaran, C Forsyth, R Lear, A Roynon, Claire Price, Ana Atti, Maria Zambon, Stephen R Knight, Jeremy N. Day, Katja Hoschler, Aarti Shah, Chetan Parmar, Rajeka Lazarus, M Lattimore, Julia Stowe, J Aeron-Thomas, J Tomlinson, L Allsop, A Abdelrazik, C Laven, Silvia D'Arcangelo, Z Naheed, A Cochrane, L Price, Emily MacNaughton, K Munro, E King, Chris Jones, S Mcwilliam, G Boyd, Caroline Kerrison, S Hamer, David W Eyre, T Trinick, J Marrs, F Adair, H Coles, Jameel Khawam, S Board, Gordon B. Mills, Mary Ramsay, Nada Ahmed, D Brooking, J Northfield, Jamie Lopez-Bernal, N Kalakonda, D Ironmonger, Shazaad Ahmad, S Taylor, A Watt, J Graves, D Flanagan, Helen Baxendale, R Penn, Louise Berry, D Corrigan, C Favager, M E Green, V Bateman, N Mahabir, J Osbourne, K Gray, Eleri Wilson-Davies, S Pai, I Knox, S Tonge, G Pottinger, M Brazil, Hayley Crawford, K Court, Daniel Harvey, Brendan A I Payne, A Arenas-Pinto, E Hanna, Robin Gopal, Henrietta U. Okafor, Frances L. Game, A Cross, Benjamin J. Stewart, Kevin K. Brown, Timothy M Reynolds, ED Lacey, V Irvine, Julie V. Robotham, A Lloyd, M Aga, D Brennan, C Loughrey, K Shipman, I Del Rosario, Stephen J. Fowler, H Hodgson, K Nimako, Ruth Simmons, Aditi Pai, S Stewart, R Druyeh, Nicholas J. White, A Bexley, E Defever, G Harrison, Trevor J. Barnes, N Wong, Natalie Gillson, S Khanduri, Sarah Wallace, M O'Kane, A Whileman, Arthur Taylor, A Houston, R Sierra, N Elumogo, Ezra Linley, A Higham, J Islam, J Ashcroft, E Underhill, D Camero, Stacey Donaldson, N Gillson, N Osuji, M Z Qazzafi, J Birch, C Sinclair, E Wellington, D Dhasmana, C Pegg, Reuben McGregor, C Norman, Alison Rodger, D Adeboyeku, L E Hughes, H Johnstone, L Gallego, Tim Brooks, Adrian Hawkins, A Selassi, P Swift, P Mercer, A Cowley, A Gibson, P Harrington, A Broadley, P Ridley, S Evans, Ywj Huang, Dunachie, SJ, and Group, SIREN Study

Subjects
medicine.medical_specialty, business.industry, Incidence (epidemiology), Hazard ratio, General Medicine, 030204 cardiovascular system & hematology, Asymptomatic, Vaccination, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, Cohort, Medicine, Population study, 030212 general & internal medicine, medicine.symptom, business, Prospective cohort study, Cohort study
Abstract

Summary Background BNT162b2 mRNA and ChAdOx1 nCOV-19 adenoviral vector vaccines have been rapidly rolled out in the UK from December, 2020. We aimed to determine the factors associated with vaccine coverage for both vaccines and documented the vaccine effectiveness of the BNT162b2 mRNA vaccine in a cohort of health-care workers undergoing regular asymptomatic testing. Methods The SIREN study is a prospective cohort study among staff (aged ≥18 years) working in publicly-funded hospitals in the UK. Participants were assigned into either the positive cohort (antibody positive or history of infection [indicated by previous positivity of antibody or PCR tests]) or the negative cohort (antibody negative with no previous positive test) at the beginning of the follow-up period. Baseline risk factors were collected at enrolment, symptom status was collected every 2 weeks, and vaccination status was collected through linkage to the National Immunisations Management System and questionnaires. Participants had fortnightly asymptomatic SARS-CoV-2 PCR testing and monthly antibody testing, and all tests (including symptomatic testing) outside SIREN were captured. Data cutoff for this analysis was Feb 5, 2021. The follow-up period was Dec 7, 2020, to Feb 5, 2021. The primary outcomes were vaccinated participants (binary ever vacinated variable; indicated by at least one vaccine dose recorded by at least one of the two vaccination data sources) for the vaccine coverage analysis and SARS-CoV-2 infection confirmed by a PCR test for the vaccine effectiveness analysis. We did a mixed-effect logistic regression analysis to identify factors associated with vaccine coverage. We used a piecewise exponential hazard mixed-effects model (shared frailty-type model) using a Poisson distribution to calculate hazard ratios to compare time-to-infection in unvaccinated and vaccinated participants and estimate the impact of the BNT162b2 vaccine on all PCR-positive infections (asymptomatic and symptomatic). This study is registered with ISRCTN, number ISRCTN11041050, and is ongoing. Findings 23 324 participants from 104 sites (all in England) met the inclusion criteria for this analysis and were enrolled. Included participants had a median age of 46·1 years (IQR 36·0–54·1) and 19 692 (84%) were female; 8203 (35%) were assigned to the positive cohort at the start of the analysis period, and 15 121 (65%) assigned to the negative cohort. Total follow-up time was 2 calendar months and 1 106 905 person-days (396 318 vaccinated and 710 587 unvaccinated). Vaccine coverage was 89% on Feb 5, 2021, 94% of whom had BNT162b2 vaccine. Significantly lower coverage was associated with previous infection, gender, age, ethnicity, job role, and Index of Multiple Deprivation score. During follow-up, there were 977 new infections in the unvaccinated cohort, an incidence density of 14 infections per 10 000 person-days; the vaccinated cohort had 71 new infections 21 days or more after their first dose (incidence density of eight infections per 10 000 person-days) and nine infections 7 days after the second dose (incidence density four infections per 10 000 person-days). In the unvaccinated cohort, 543 (56%) participants had typical COVID-19 symptoms and 140 (14%) were asymptomatic on or 14 days before their PCR positive test date, compared with 29 (36%) with typical COVID-19 symptoms and 15 (19%) asymptomatic in the vaccinated cohort. A single dose of BNT162b2 vaccine showed vaccine effectiveness of 70% (95% CI 55–85) 21 days after first dose and 85% (74–96) 7 days after two doses in the study population. Interpretation Our findings show that the BNT162b2 vaccine can prevent both symptomatic and asymptomatic infection in working-age adults. This cohort was vaccinated when the dominant variant in circulation was B1.1.7 and shows effectiveness against this variant. Funding Public Health England, UK Department of Health and Social Care, and the National Institute for Health Research.

Published
2021

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