Safety and efficacy of the ChAdOx1 nCoV-19 vaccine (AZD1222) against SARS-CoV-2: an interim analysis of four randomised controlled trials in Brazil, South Africa, and the UK
Merryn Voysey(University of Oxford), Sue Ann Costa Clemens(University of Siena), Shabir A. Madhi(South African Medical Research Council), Lily Yin Weckx(Universidade Federal de São Paulo), Pedro M. Folegatti(University of Oxford), Parvinder K. Aley(University of Oxford), Brian Angus(University of Oxford), Vicky L. Baillie(University of the Witwatersrand), Shaun Barnabas(Stellenbosch University), Qasim Bhorat(Soweto CTC), Sagida Bibi(University of Oxford), Carmen Briner(University of the Witwatersrand), Paola Cicconi(University of Oxford), Andrea M. Collins(Liverpool School of Tropical Medicine), Rachel Colin-Jones(University of Oxford), Clare Cutland(University of the Witwatersrand), Thomas C. Darton(Sheffield Teaching Hospitals NHS Foundation Trust), Keertan Dheda(University of London), C.J. Duncan(Newcastle upon Tyne Hospitals NHS Foundation Trust), Katherine R. W. Emary(University of Oxford), Katie Ewer(University of Oxford), Lee Fairlie(University of the Witwatersrand), Saul N. Faust(University Hospital Southampton NHS Foundation Trust), Shuo Feng(University of Oxford), Daniela M. Ferreira(Liverpool School of Tropical Medicine), Adam Finn(University Hospitals Bristol NHS Foundation Trust), Anna L. Goodman(St Thomas' Hospital), Catherine Green(University Hospitals Birmingham NHS Foundation Trust), Christopher Green(University Hospitals Birmingham NHS Foundation Trust), Paul T. Heath(St George's, University of London), Catherine Hill(University of the Witwatersrand), Helen Hill(Liverpool School of Tropical Medicine), Ian Hirsch(AstraZeneca (United Kingdom)), Susanne H. Hodgson(University of Oxford), Alane Izu(Right to Care), Susan Jackson(University of Oxford), Daniel Jenkin(University of Oxford), Carina C. D. Joe(University of Oxford), Simon Kerridge(University of Oxford), Anthonet Koen(Right to Care), Gaurav Kwatra(University of the Witwatersrand), Rajeka Lazarus(North Bristol NHS Trust), Alison M. Lawrie(University of Oxford), Alice Lelliott(University of Oxford), Vincenzo Libri(UCL Biomedical Research Centre), Patrick Lillie(University of Hull), Raburn M. Mallory(AstraZeneca (United Kingdom)), Ana Verena Almeida Mendes(Escola Bahiana de Medicina e Saúde Pública), Eveline Pı́polo Milan(Universidade Federal do Rio Grande do Norte), Angela M. Minassian(University of Oxford), Alastair McGregor(London North West Healthcare NHS Trust), Hazel Morrison(University of Oxford), Yama F Mujadidi(University of Oxford), Anusha Nana(University of the Witwatersrand), Peter O’Reilly(University of Oxford), Sherman D. Padayachee(Setshaba Research Centre), Ana Maria Pittella(Universidade Unigranrio), Emma Plested(University of Oxford), Katrina M. Pollock(NIHR Imperial Biomedical Research Centre), Maheshi Ramasamy(University of Oxford), Sarah Rhead(University of Oxford), Alexandre Vargas Schwarzbold(Universidade Federal de Santa Maria), Nisha Singh(University of Oxford), Darren Smith(University of Glasgow), Rinn Song(Boston Children's Hospital), Matthew D. Snape(University of Oxford), Eduardo Sprinz(Universidade Federal do Rio Grande do Sul), Rebecca Sutherland(Western General Hospital), Richard Tarrant(University of Oxford), Emma C. Thomson(MRC University of Glasgow Centre for Virus Research), M. Estée Török(University of Cambridge), Mark Toshner(Papworth Hospital NHS Foundation Trust), David P. J. Turner(Nottingham University Hospitals NHS Trust), Johan Vekemans(AstraZeneca (United Kingdom)), Tonya Villafana(AstraZeneca (United Kingdom)), Marion Watson(University of Oxford), Christopher J. Williams(Aneurin Bevan University Health Board), Alexander D. Douglas(University of Oxford), Adrian V. S. Hill(University of Oxford), Teresa Lambe(University of Oxford), Sarah C. Gilbert(University of Oxford), Andrew J. Pollard(University of Oxford), Marites Aban, Fatola Abayomi, Kushala W.M. Abeyskera, Jeremy Aboagye, Matthew Adam, Kirsty Adams, James P. Adamson, Yemi Adelaja, Gbadebo Adewetan, Syed Adlou, Khatija Ahmed, Yasmeen Akhalwaya, Saajida Akhalwaya, Andrew Alcock(University of London), Aabidah Ali(University of London), Elizabeth Allen, Lauren Allen, Thamires C. D. S. C Almeida, Mariana Alves, Fábio Ferreira Amorim, Foteini Andritsou, Rachel Anslow, Matthew Appleby, Edward H. Arbe-Barnes, Mark P. Ariaans, Beatriz Arns, Laiana Arruda, Paula De Almeida Azi, Lorena Azi, Gavin Babbage, Catherine Bailey, Kenneth F. Baker, Megan Baker, Natalie Baker, Philip Baker, Lisa Baldwin, Ioana Baleanu, Danieli Bandeira, Anna Bara, Marcella A.S. Barbosa, Debbie Barker, Gavin Barlow, Eleanor Barnes, Andrew Barr, Jordan R. Barrett, Jessica Barrett, Louise Bates, Alexander Batten, Kirsten Beadon, Emily Beales, Rebecca Beckley, Sandra Belij‐Rammerstorfer, Jonathan Bell, Duncan Bellamy(University of London), Nancy Bellei, Sue Belton, Adam Berg, Laura M. Bermejo, Eleanor Berrie, Lisa Berry, Daniella Berzenyi, Amy Beveridge, Kevin R. Bewley, Helen Bexhell, Sutika Bhikha, As’ad E. Bhorat, Zaheda E. Bhorat, Else M. Bijker, Geeta Birch, Sarah Birch, Adam Bird, Olivia Bird, Karen Bisnauthsing, Mustapha Bittaye, K. Blackstone(University of London), Luke Blackwell, Heather Bletchly, Caitlin L. Blundell, Susannah R. Blundell, Pritesh Bodalia, Bruno Cruz Boettger, Emma Bolam, Elena Boland, Daan Bormans, Nicola Borthwick, Francesca Bowring, Amy Boyd, Penny Bradley, Tanja Brenner, Phillip J. Brown, Claire Brown, Charlie Brown-O’Sullivan, S Bruce, Emily Brunt, Ruaridh Buchan, William Budd, Yusuf A. Bulbulia, Melanie Bull, Jamie Burbage, Hassan Burhan, Aileen Burn, Karen R. Buttigieg, Nicholas Byard, Ingrid Cabera Puig, Gloria Calderón, Anna Calvert, Susana Camara, Michelangelo Cao, Federica Cappuccini, João C. R. Cardoso, Melanie Carr, Miles W. Carroll, Andrew Carson‐Stevens(University of London), Yasmin de M. Carvalho, José Antônio Mainardi de Carvalho, Helen R. Casey, Paul Cashen(University of London), Thaís Castro Ribeiro, Lucía Carratalá-Castro, Katrina Cathie, Ana Cavey, José Cerbino-Neto, Jim Chadwick, David Chapman, Sue Charlton, Irina Chelysheva, Oliver Chester, Sunder Chita, Jee-Sun Cho, Liliana Cifuentes, Elizabeth Clark, Matthew Clark, Andrea Clarke, Elizabeth Clutterbuck, Sarah L.K. Collins, Christopher P. Conlon, Sean Connarty, Naomi S. Coombes, Cushla Cooper, Rachel Cooper, Lynne Cornelissen, Tumena Corrah, Catherine Cosgrove, Tony Cox, Wendy E.M. Crocker, Sarah Crosbie, Lorraine Cullen, Dan Cullen, Debora R.M.F. Cunha, Christina J. Cunningham, Fiona C. Cuthbertson, Suzete Nascimento Farias da Guarda, Larissa P. da Silva, Brad E. Damratoski, Zsofia Danos, Maria T.D.C. Dantas, Paula Darroch, Mehreen S. Datoo, Chandrabali Datta, Malika Davids, Sarah L. Davies, H. Dele Davies, Elizabeth J. Davis, Judith A. Davis, John D. Davis, Maristela Miyamoto de Nobrega, Lis Moreno De Oliveira Kalid, David Dearlove, Tesfaye Demissie, Amisha Desai, Stefania Di Marco, Claudio Di Maso, Maria Isabel Saraiva Dinelli, Tanya Dinesh, Claire Docksey, Christina Dold, Tao Dong, Francesca R. Donnellan, Tannyth Dos Santos, Thainá G. dos Santos, Erika Pachecho Dos Santos, Naomi Douglas(University of London), Charlotte Downing, Jonathan Drake, Rachael Drake-Brockman, Kimberley Driver, Ruth Drury, Susanna Dunachie, Benjamin Durham, Lidiana Dutra, Nicholas Easom, Samual van Eck, Mandy Edwards, Nick J. Edwards, Omar M. El Muhanna, Sean C. Elias, Mike Elmore, Marcus Rex English, Alisgair Esmail, Yakub Moosa Essack, Eoghan C. W. Farmer, Mutjaba Farooq, Madi Farrar, Leonard Farrugia, Beverley Faulkner, Sofiya Fedosyuk, Sally Felle, Shuo Feng(University of Oxford), Carla Ferreira Da Silva, Samantha Field, Richard Fisher, Amy Flaxman, James L. K. Fletcher, Hazel Fofie, Henry Fok, Karen Ford, Jamie Fowler, Pedro Henrique Almeida Fraiman, Emma Francis, Marília Miranda Franco, John Frater, M Freire, Samantha H. Fry, Sabrina Fudge, Julie Furze, Michelle Fuskova, Pablo Galian-Rubio, Eva Galiza, Harriet Garlant, Madita Gavrila, A Geddes, Karyna A. Gibbons, Ciarán Gilbride, Hardeep Singh Gill, Sharon A. Glynn, Kerry Godwin, Karishma Gokani, Ursula Carvalho Goldoni, Maria Goncalves, Isabela G. S. Gonzalez, Jayne Goodwin, Amina Goondiwala, Katherine Gordon-Quayle(University of London), Giacomo Gorini, Janet Grab, Lara Gracie, Melanie Greenland, Nicola M. Greenwood, Johann Greffrath, Marisa Groenewald, Leonardo Grossi, Gaurav Gupta, Mark J. Hackett, Bassam Hallis, Mainga Hamaluba, Elizabeth Hamilton, Joseph Hamlyn, Daniel Hammersley, Aidan T. Hanrath, Brama Hanumunthadu, Stephanie A. Harris, Clair Harris, Tara Harris, T. D. Harrison, Daisy Harrison, Thomas C. Hart, Birgit Hartnell, Shadin Hassan, John Haughney, Sophia Hawkins, Jodie Hay, Ian M. Head, John A. Henry, Macarena Hermosin Herrera, David Hettle, Jennifer Hill, Gina Hodges, Elizea Horne, Mimi M. Hou, Catherine Houlihan, Elizabeth Howe, Nicola Howell, Jonathan Humphreys, Holly E. Humphries, Katrina Hurley, Claire Huson, Angela Hyder-Wright, Catherine Hyams, Sabina Ikram, Alka Ishwarbhai, Monica Ivan, Poppy Iveson, Vidyashankara Iyer, Frederic Jackson, Jeanne De Jager, Shameem Z. Jaumdally, Helen Jeffers, Natasha Jesudason, Bryony A. Jones(UCL Biomedical Research Centre), Kathryn Jones(UCL Biomedical Research Centre), Elizabeth Jones(UCL Biomedical Research Centre), Christopher Jones(UCL Biomedical Research Centre), Marianna Rocha Jorge, Aylin Jose, Amar Joshi, Eduardo A.M.S. Júnior, Joanne Kadziola, Reshma Kailath, Faeeza Kana, Konstantinos Karampatsas, Mwila Kasanyinga, Jade Keen, Elizabeth J. Kelly, Dearbhla Kelly, Debbie M. Kelly, Sarah Kelly, David Kerr, Renato de Ávila Kfouri, Liaquat Khan, Baktash Khozoee, Sarah Kidd, Annabel Killen, Jasmin Kinch, Patrick Kinch, Lloyd D. W. King, Thomas B. King, Lucy Kingham, Paul Klenerman(University of London), Francesca Knapper, Julian C. Knight, Daniel Knott, Stanislava Koleva, Matilda Lang, Gail Lang, Colin W. Larkworthy, Jessica P. J. Larwood, Rebecca‐Jane Law(University of London), Erica Lazarus, Amanda Leach, Emily A. Lees, Nana‐Marie Lemm, Alvaro Edson Ramos Lessa, Stephanie Leung, Yuanyuan Li(University of London), Amelia M. Lias, Kostas Liatsikos, Aline Linder, Samuel Lipworth, Shuchang Liu, Xinxue Liu, Adam Lloyd, Stephanie Lloyd, Lisa Loew, Raquel Lopez Ramon, Leandro Bonecker Lora, Vicki Lowthorpe, Kléber Giovanni Luz, Jonathan Macdonald, Gordon MacGregor, Meera Madhavan, David O. Mainwaring, Edson Makambwa, Rebecca Makinson, Mookho Malahleha, Ross Malamatsho, Garry Mallett, Kushal Mansatta, Takalani Maoko, Katlego Mapetla, Natalie G. Marchevsky, Spyridoula Marinou, Emma Marlow, Gabriela N. Marques, Paula Marriott, Richard P. Marshall, Julia L. Marshall, Flávia J. Martins, Masebole Masenya, Mduduzi Masilela, Shauna K. Masters, Moncy Mathew, Hosea Matlebjane, Kedidimetse Matshidiso, Olga Mazur, Andrea Mazzella, Hugh McCaughan, Joanne McEwan, Joanna McGlashan, Lorna McInroy, Zoe McIntyre, Daniela McLenaghan, Nicky McRobert, Steve McSwiggan, Clare Megson, Savviz Mehdipour, Wilma Meijs, Renata Mendonça, Alexander J. Mentzer, Neginsadat Mirtorabi, Celia Mitton, Sibusiso Mnyakeni, Fiona Moghaddas, Kgaogelo Molapo, Mapule Moloi, Maria Moore, M. Isabel Moraes-Pinto, Marni Moran, Ella Morey, Róisín Morgans, Susan Morris, Sheila Morris, Helen Morris, Franca Morselli, Gertraud Morshead, Richard Morter, Lynelle Mottal, Andrew Moultrie(University of London), Nathifa Moya, Mushiya Mpelembue, Sibekezelo Msomi, Yvonne Mugodi, Ekta Mukhopadhyay, Jilly Muller, Alasdair Munro, Claire Munro, Sarah Murphy, Philomena Mweu, Celia Hatsuko Myasaki, Gurudutt Naik, Kush Naker, Eleni Nastouli, Abida Nazir, Bongani Ndlovu, F Neffa, Cecilia Njenga, Helena Carolina Noal, Andrés Noé, Gabrielle Gonçalves de Novaes, Fay L. Nugent, Géssika Lanzillo A. Nunes, Katie M. O’Brien(UCL Biomedical Research Centre), Daniel O’Connor, Miranda Odam, Suzette Oelofse, Blanché Oguti, Victoria Olchawski, Neil J. Oldfield, Marianne Garcia de Oliveira, Catarina Oliveira, A Oosthuizen, Paula O'Reilly(University of Oxford), Piper Osborne, David R. Owen, Lydia Owen, DR Owens, Nelly Owino, Mihaela Pacurar, Brenda Lopes Paiva, Edna M.F. Palhares, Susan Palmer, S. N. PARKINSON, Helena Parracho, Karen Parsons, Dipak Patel, Bhumika Patel, Faeezah Patel, Kelly Patel, Maia Patrick-Smith, Ruth Payne, Yanchun Peng, Elizabeth J. Penn, Anna Pennington, Marco Polo Peralta Álvarez, James Perring, Nicola Perry, Rubeshan Perumal, Sahir Yusuf Petkar, Tricia Philip, Daniel J. Phillips, Jennifer Phillips, Mary Kgomotso Phohu, Lorinda Pickup, Sonja Pieterse, Jo Piper(University of London), Dimitra Pipini, Mary Plank, Joan Du Plessis, S. Pollard(University of London), Jennifer Pooley, Anil Pooran, Ian Poulton, Claire Powers, Fernando B. Presa, David Price, Vivien Price, Marcelo Ribeiro Primeira, Pamela C. Proud, Samuel Provstgaard-Morys, Sophie Pueschel, David Pulido, Sheena Quaid, Ria Rabara, Alexandra Radford, Kajal Radia, Durga Rajapaska, Thurkka Rajeswaran, Alberto San Francisco Ramos, Fernando Ramos Lopez, Tommy Rampling, Jade Rand, Helen Ratcliffe, Tom Rawlinson, David Rea, Byron Rees, Jesús Reiné, Mila Resuello-Dauti, Emilia Reyes Pabon, Carla M. Ribiero, Marivic Ricamara, Alex Richter, Neil Ritchie, Adam Ritchie, Alexander J. Robbins, Hannah Roberts, Ryan Robinson, Hannah Robinson, Talita Trevizani Rocchetti, Beatriz Pinho Rocha, Sophie Roche, Christine S. Rollier, Louisa Rose, Amy Russell, Lindie Rossouw, Simon Royal, Indra Rudiansyah, Sarah Ruiz, Stephen Saich, Claudia Sala, Jessica Sale, Ahmed M. Salman, Natalia Salvador, Stephannie Salvador, Milla Dias Sampaio, Annette D. Samson, Amada Sanchez-Gonzalez, Helen Sanders, Katherine Sanders(University of London), Erika Santos, Mayara F.S. Santos Guerra, Iman Satti, Jack E. Saunders, Caroline Saunders, Aakifah Bibi Arif Sayed, Ina Schim van der Loeff, Annina B. Schmid, Ella Schofield, Gavin Screaton, Samiullah Seddiqi, Rameswara R. Segireddy, Roberta Senger, Sonia Serrano, Rajiv Shah, Imam H. Shaik, Hannah Sharpe, Katherine Sharrocks(University of London), R. H. Shaw, Adam Shea, Amy Shepherd, James G. Shepherd, Farah Shiham, Emad Sidhom, Sarah E. Silk, Antonio Carlos da Silva Moraes, Gilberto Silva‐Junior, Laura Silva-Reyes, Anderson Donelli da Silveira, Mariana B.V. Silveira, J. Sinha, Donal Skelly, Daniel C. Smith, N Smith, H. SMITH, David J. Smith, Catherine C. Smith, Airanuedida Silva Soares, Tiago Soares, Carla Solórzano, Guilherme Geraldo Lovato Sorio, Kim Sorley, Tiffany Sosa-Rodriguez, Cinthia M.C.D.L. Souza, Bruno Solano de Freitas Souza, Alessandra R. Souza, Alexandra J. Spencer, Fernanda Spina, Louise Spoors, Lizzie Stafford, Imogen Stamford, Igor Starinskij, Ricardo Stein, Jill Steven, Lisa Stockdale, Lisa V. Stockwell, Louise Strickland, Arabella C. Stuart, Ann Sturdy, Natalina Sutton, Anna Szigeti, Abdessamad Tahiri‐Alaoui, Rachel Tanner, Carol Taoushanis, Alexander W. Tarr, Keja Taylor, Ursula Taylor, Iona J. Taylor, Justin Taylor, Rebecca te Water Naudé, Yrene Themistocleous, Andreas C. Themistocleous, Merin Thomas, Kelly Thomas, Tonia M. Thomas, Asha Thombrayil, Fawziyah Thompson, Amber Thompson, Kevin Thompson, Ameeka Thompson, Julia Thomson, V Thornton-Jones, Patrick J. Tighe, Lygia Accioly Tinoco, Gerlynn Tiongson, Bonolo Tladinyane, Michele Tomasicchio, Adriana Tomić, Susan Tonks, James Towner, Nguyen Tran, Julia A. Tree, Gerry Trillana, Charlotte Trinham, Rose Trivett, Adam Truby, Betty Lebogang Tsheko, Aadil Turabi, Richard Turner, Cheryl Turner, Marta Ulaszewska, Benjamin R. Underwood, Rachel Varughese, Dennis Verbart, Marije K. Verheul, Iason Vichos, Taiane Alves Vieira, Claire S. Waddington, Laura M. Walker, Erica J. Wallis, Matthew E. Wand, Deborah Warbick, T. M. Wardell, George M. Warimwe, Sarah Warren, Bridget Watkins, Ekaterina Watson(University of London), Stewart Webb, Alice Webb-Bridges(University of London), Angela C Webster, Jessica Welch, Jeanette Wells, Alison C. West, Caroline White, Rachel White, Paul Williams, Rachel Williams, Rebecca Winslow, Mark Woodyer, Andrew Worth, Danny Wright, Marzena Wroblewska, Andy Yao, Rafael Leal Zimmer, Dalila Zizi, Peter Zuidewind
Cited by 5,001Open Access
Abstract
BACKGROUND: A safe and efficacious vaccine against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), if deployed with high coverage, could contribute to the control of the COVID-19 pandemic. We evaluated the safety and efficacy of the ChAdOx1 nCoV-19 vaccine in a pooled interim analysis of four trials. METHODS: viral particles (standard dose; SD/SD cohort); a subset in the UK trial received a half dose as their first dose (low dose) and a standard dose as their second dose (LD/SD cohort). The primary efficacy analysis included symptomatic COVID-19 in seronegative participants with a nucleic acid amplification test-positive swab more than 14 days after a second dose of vaccine. Participants were analysed according to treatment received, with data cutoff on Nov 4, 2020. Vaccine efficacy was calculated as 1 - relative risk derived from a robust Poisson regression model adjusted for age. Studies are registered at ISRCTN89951424 and ClinicalTrials.gov, NCT04324606, NCT04400838, and NCT04444674. FINDINGS: =0·010). Overall vaccine efficacy across both groups was 70·4% (95·8% CI 54·8-80·6; 30 [0·5%] of 5807 vs 101 [1·7%] of 5829). From 21 days after the first dose, there were ten cases hospitalised for COVID-19, all in the control arm; two were classified as severe COVID-19, including one death. There were 74 341 person-months of safety follow-up (median 3·4 months, IQR 1·3-4·8): 175 severe adverse events occurred in 168 participants, 84 events in the ChAdOx1 nCoV-19 group and 91 in the control group. Three events were classified as possibly related to a vaccine: one in the ChAdOx1 nCoV-19 group, one in the control group, and one in a participant who remains masked to group allocation. INTERPRETATION: ChAdOx1 nCoV-19 has an acceptable safety profile and has been found to be efficacious against symptomatic COVID-19 in this interim analysis of ongoing clinical trials. FUNDING: UK Research and Innovation, National Institutes for Health Research (NIHR), Coalition for Epidemic Preparedness Innovations, Bill & Melinda Gates Foundation, Lemann Foundation, Rede D'Or, Brava and Telles Foundation, NIHR Oxford Biomedical Research Centre, Thames Valley and South Midland's NIHR Clinical Research Network, and AstraZeneca.
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