Cardiff University | Prifysgol Caerdydd ORCA
Online Research @ Cardiff 
WelshClear Cookie - decide language by browser settings

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

Voysey, Merryn, Clemens, Sue Ann Costa, Madhi, Shabir A., Weckx, Lily Y., Folegatti, Pedro M., Aley, Parvinder K., Angus, Brian, Baillie, Vicky L., Barnabas, Shaun L., Bhorat, Qasim E., Bibi, Sagida, Briner, Carmen, Cicconi, Paola, Collins, Andrea M., Colin-Jones, Rachel, Cutland, Clare L., Darton, Thomas C., Dheda, Keertan, Duncan, Christopher J. A., Emary, Katherine R. W., Ewer, Katie J., Fairlie, Lee, Faust, Saul N., Feng, Shuo, Ferreira, Daniela M., Finn, Adam, Goodman, Anna L., Green, Catherine M., Green, Christopher A., Heath, Paul T., Hill, Catherine, Hill, Helen, Hirsch, Ian, Hodgson, Susanne H. C., Izu, Alane, Jackson, Susan, Jenkin, Daniel, Joe, Carina C. D., Kerridge, Simon, Koen, Anthonet, Kwatra, Gaurav, Lazarus, Rajeka, Lawrie, Alison M., Lelliott, Alice, Libri, Vincenzo, Lillie, Patrick J., Mallory, Raburn, Mendes, Ana V .A., Milan, Eveline P., Minassian, Angela M., McGregor, Alastair, Morrison, Hazel, Mujadidi, Yama F., Nana, Anusha, O'Reilly, Peter J., Padayachee, Sherman D., Pittella, Ana, Plested, Emma, Pollock, Katrina M., Ramasamy, Maheshi N., Rhead, Sarah, Schwarzbold, Alexandre V., Singh, Nisha, Smith, Andrew, Song, Rinn, Snape, Matthew D., Sprinz, Eduardo, Sutherland, Rebecca K., Tarrant, Richard, Thomson, Emma C., Török, M Estée, Toshner, Mark, Turner, David P. J., Vekemans, Johan, Villafana, Tonya L., Watson, Marion E. E., Williams, Christopher J., Douglas, Alexander D., Hill, Adrian V. S., Lambe, Teresa, Gilbert, Sarah C, Pollard, Andrew J, Aban, Marites, Abayomi, Fatola, Abeyskera, Kushala, Aboagye, Jeremy, Adam, Matthew, Adams, Kirsty, Adamson, James, Adelaja, Yemi A., Adlou, Syed, Ahmed, Khatija, Akhalwaya, Yasmeen, Akhalwaya, Saajida, Alcock, Andrew, Ali, Aabidah, Allen, Elizabeth R., Allen, Lauren, Almeida, Thamires C. D. S. C, Alves, Mariana P.S., Amorim, Fabio, Andritsou, Foteini, Anslow, Rachel, Appleby, Matthew, Arbe-Barnes, Edward H., Ariaans, Mark P., Arns, Beatriz, Arruda, Laiana, Awedetan, Gbadebo, Azi, Paula, Azi, Lorena, Babbage, Gavin, Bailey, Catherine, Baker, Kenneth F., Baker, Megan, Baker, Natalie, Baker, Philip, Baldwin, Lisa, Baleanu, Ioana, Bandeira, Danieli, Bara, Anna, Barbosa, Marcella A.S., Barker, Debbie, Barlow, Gavin D., Barnes, Eleanor, Barr, Andrew S., Barrett, Jordan R., Barrett, Jessica, Bates, Louise, Batten, Alexander, Beadon, Kirsten, Beales, Emily, Beckley, Rebecca, Belij-Rammerstorfer, Sandra, Bell, Jonathan, Bellamy, Duncan, Bellei, Nancy, Belton, Sue, Berg, Adam, Bermejo, Laura, Berrie, Eleanor, Berry, Lisa, Berzenyi, Daniella, Beveridge, Amy, Bewley, Kevin R., Bexhell, Helen, Bhikha, Sutika, Bhorat, Asad E., Bhorat, Zaheda E., Bijker, Else, Birch, Geeta, Birch, Sarah, Bird, Adam, Bird, Olivia, Bisnauthsing, Karen, Bittaye, Mustapha, Blackstone, Katherine, Blackwell, Luke, Bletchly, Heather, Blundell, Caitlin L., Blundell, Susannah R., Bodalia, Pritesh, Boettger, Bruno C., Bolam, Emma, Boland, Elena, Bormans, Daan, Borthwick, Nicola, Bowring, Francesca, Boyd, Amy, Bradley, Penny, Brenner, Tanja, Brown, Phillip, Brown, Claire, Brown-O'Sullivan, Charlie, Bruce, Scott, Brunt, Emily, Buchan, Ruaridh, Budd, William, Bulbulia, Yusuf A., Bull, Melanie, Burbage, Jamie, Burhan, Hassan, Burn, Aileen, Buttigieg, Karen R., Byard, Nicholas, Cabera Puig, Ingrid, Calderon, Gloria, Calvert, Anna, Camara, Susana, Cao, Michelangelo, Cappuccini, Federica, Cardoso, João R., Carr, Melanie, Carroll, Miles W., Carson-Stevens, Andrew, Carvalho, Yasmin de M., Carvalho, José A.M., Casey, Helen R., Cashen, Paul, Castro, Thais, Castro, Lucia Carratala, Cathie, Katrina, Cavey, Ana, Cerbino-Neto, José, Chadwick, Jim, Chapman, David, Charlton, Sue, Chelysheva, Irina, Chester, Oliver, Chita, Sunder, Cho, Jee-Sun, Cifuentes, Liliana, Clark, Elizabeth, Clark, Matthew, Clarke, Andrea, Clutterbuck, Elizabeth A., Collins, Sarah L.K., Conlon, Christopher P., Connarty, Sean, Coombes, Naomi, Cooper, Cushla, Cooper, Rachel, Cornelissen, Lynne, Corrah, Tumena, Cosgrove, Catherine, Cox, Tony, Crocker, Wendy E.M., Crosbie, Sarah, Cullen, Lorraine, Cullen, Dan, Cunha, Debora R.M.F., Cunningham, Christina, Cuthbertson, Fiona C., Da Guarda, Suzete N. Farias, da Silva, Larissa P., Damratoski, Brad E., Danos, Zsofia, Dantas, Maria T.D.C., Darroch, Paula, Datoo, Mehreen S., Datta, Chandrabali, Davids, Malika, Davies, Sarah L., Davies, Hannah, Davis, Elizabeth, Davis, Judith, Davis, John, De Nobrega, Maristela M.D., De Oliveira Kalid, Lis Moreno, Dearlove, David, Demissie, Tesfaye, Desai, Amisha, Di Marco, Stefania, Di Maso, Claudio, Dinelli, Maria I.S., Dinesh, Tanya, Docksey, Claire, Dold, Christina, Dong, Tao, Donnellan, Francesca R., Dos Santos, Tannyth, dos Santos, Thainá G., Dos Santos, Erika Pachecho, Douglas, Naomi, Downing, Charlotte, Drake, Jonathan, Drake-Brockman, Rachael, Driver, Kimberley, Drury, Ruth, Dunachie, Susanna J., Durham, Benjamin S., Dutra, Lidiana, Easom, Nicholas J.W., van Eck, Samual, Edwards, Mandy, Edwards, Nick J., El Muhanna, Omar M., Elias, Sean C., Elmore, Mike, English, Marcus, Esmail, Alisgair, Essack, Yakub Moosa, Farmer, Eoghan, Farooq, Mutjaba, Farrar, Madi, Farrugia, Leonard, Faulkner, Beverley, Fedosyuk, Sofiya, Felle, Sally, Feng, Shuo, Ferreira Da Silva, Carla, Field, Samantha, Fisher, Richard, Flaxman, Amy, Fletcher, James, Fofie, Hazel, Fok, Henry, Ford, Karen J., Fowler, Jamie, Fraiman, Pedro H.A., Francis, Emma, Franco, Marilia M., Frater, John, Freire, Marilúcia S.M., Fry, Samantha H., Fudge, Sabrina, Furze, Julie, Fuskova, Michelle, Galian-Rubio, Pablo, Galiza, Eva, Garlant, Harriet, Gavrila, Madita, Geddes, Ailsa, Gibbons, Karyna A., Gilbride, Ciaran, Gill, Hardeep, Glynn, Sharon, Godwin, Kerry, Gokani, Karishma, Goldoni, Ursula Carvalho, Goncalves, Maria, Gonzalez, Isabela G.S., Goodwin, Jayne, Goondiwala, Amina, Gordon-Quayle, Katherine, Gorini, Giacomo, Grab, Janet, Gracie, Lara, Greenland, Melanie, Greenwood, Nicola, Greffrath, Johann, Groenewald, Marisa M., Grossi, Leonardo, Gupta, Gaurav, Hackett, Mark, Hallis, Bassam, Hamaluba, Mainga, Hamilton, Elizabeth, Hammersley, Daniel, Hanrath, Aidan T., Hanumunthadu, Brama, Harris, Stephanie A., Harris, Clair, Harris, Tara, Harrison, Thomas D., Harrison, Daisy, Hart, Thomas C., Hartnell, Birgit, Hassan, Shadin, Haughney, John, Hawkins, Sophia, Hay, Jodie, Head, Ian, Henry, John, Hermosin Herrera, Macarena, Hettle, David B., Hill, Jennifer, Hodges, Gina, Horne, Elizea, Hou, Mimi M., Houlihan, Catherine, Howe, Elizabeth, Howell, Nicola, Humphreys, Jonathan, Humphries, Holly E., Hurley, Katrina, Huson, Claire, Hyder-Wright, Angela, Hyamns, Catherine, Ikram, Sabina, Ishwarbhai, Alka, Ivan, Monica, Iveson, Poppy, Iyer, Vidyashankara, Jackson, Frederic, De Jager, Jeanne, Jaumdally, Shameem, Jeffers, Helen, Jesudason, Natasha, Jones, Bryony, Jones, Kathryn, Jones, Elizabeth, Jones, Christopher, Jorge, Marianna Rocha, Jose, Aylin, Joshi, Amar, Júnior, Eduardo A.M.S., Kadziola, Joanne, Kailath, Reshma, Kana, Faeeza, Karampatsas, Konstantinos, Kasanyinga, Mwila, Keen, Jade, Kelly, Elizabeth J., Kelly, Dearbhla M., Kelly, Debbie, Kelly, Sarah, Kerr, David, Kfouri, Renato de Ávila, Khan, Liaquat, Khozoee, Baktash, Kidd, Sarah, Killen, Annabel, Kinch, Jasmin, Kinch, Patrick, King, Lloyd D.W., King, Thomas B., Kingham, Lucy, Klenerman, Paul, Knapper, Francesca, Knight, Julian C., Knott, Daniel, Koleva, Stanislava, Lang, Matilda, Lang, Gail, Larkworthy, Colin W., Larwood, Jessica P.J., Law, Rebecca, Lazarus, Erica M., Leach, Amanda, Lees, Emily A., Lemm, Nana-Marie, Lessa, Alvaro, Leung, Stephanie, Li, Yuanyuan, Lias, Amelia M., Liatsikos, Kostas, Linder, Aline, Lipworth, Samuel, Liu, Shuchang, Liu, Xinxue, Lloyd, Adam, Lloyd, Stephanie, Loew, Lisa, Lopez Ramon, Raquel, Lora, Leandro, Lowthorpe, Vicki, Luz, Kleber, MacDonald, Jonathan C., MacGregor, Gordon, Madhavan, Meera, Mainwaring, David O., Makambwa, Edson, Makinson, Rebecca, Malahleha, Mookho, Malamatsho, Ross, Mallett, Garry, Mansatta, Kushal, Maoko, Takalani, Mapetla, Katlego, Marchevsky, Natalie G., Marinou, Spyridoula, Marlow, Emma, Marques, Gabriela N., Marriott, Paula, Marshall, Richard P., Marshall, Julia L., Martins, Flávia J., Masenya, Masebole, Masilela, Mduduzi, Masters, Shauna K., Mathew, Moncy, Matlebjane, Hosea, Matshidiso, Kedidimetse, Mazur, Olga, Mazzella, Andrea, McCaughan, Hugh, McEwan, Joanne, McGlashan, Joanna, McInroy, Lorna, McIntyre, Zoe, McLenaghan, Daniela, McRobert, Nicky, McSwiggan, Steve, Megson, Clare, Mehdipour, Savviz, Meijs, Wilma, Mendonça, Renata N.Á., Mentzer, Alexander J., Mirtorabi, Neginsadat, Mitton, Celia, Mnyakeni, Sibusiso, Moghaddas, Fiona, Molapo, Kgaogelo, Moloi, Mapule, Moore, Maria, Moraes-Pinto, M. Isabel, Moran, Marni, Morey, Ella, Morgans, Róisín, Morris, Susan, Morris, Sheila, Morris, Helen C., Morselli, Franca, Morshead, Gertraud, Morter, Richard, Mottal, Lynelle, Moultrie, Andrew, Moya, Nathifa, Mpelembue, Mushiya, Msomi, Sibekezelo, Mugodi, Yvonne, Mukhopadhyay, Ekta, Muller, Jilly, Munro, Alasdair, Munro, Claire, Murphy, Sarah, Mweu, Philomena, Myasaki, Celia Hatsuko, Naik, Gurudutt, Naker, Kush, Nastouli, Eleni, Nazir, Abida, Ndlovu, Bongani, Neffa, Fabio, Njenga, Cecilia, Noal, Helena, Noé, Andrés, Novaes, Gabrielle, Nugent, Fay L., Nunes, Géssika, O'Brien, Katie, O'Connor, Daniel, Odam, Miranda, Oelofse, Suzette, Oguti, Blanche, Olchawski, Victoria, Oldfield, Neil J., Oliveira, Marianne G., Oliveira, Catarina, Oosthuizen, Angela, O'Reilly, Paula, Osborne, Piper, Owen, David R.J., Owen, Lydia, Owens, Daniel, Owino, Nelly, Pacurar, Mihaela, Paiva, Brenda V.B., Palhares, Edna M.F., Palmer, Susan, Parkinson, Sivapriyai, Parracho, Helena M.R.T., Parsons, Karen, Patel, Dipak, Patel, Bhumika, Patel, Faeezah, Patel, Kelly, Patrick-Smith, Maia, Payne, Ruth O., Peng, Yanchun, Penn, Elizabeth J., Pennington, Anna, Peralta Alvarez, Marco Polo, Perring, James, Perry, Nicola, Perumal, Rubeshan, Petkar, Sahir, Philip, Tricia, Phillips, Daniel J., Phillips, Jennifer, Phohu, Mary Kgomotso, Pickup, Lorinda, Pieterse, Sonja, Piper, Jo, Pipini, Dimitra, Plank, Mary, Du Plessis, Joan, Pollard, Samuel, Pooley, Jennifer, Pooran, Anil, Poulton, Ian, Powers, Claire, Presa, Fernando B., Price, David A., Price, Vivien, Primeira, Marcelo, Proud, Pamela C., Provstgaard-Morys, Samuel, Pueschel, Sophie, Pulido, David, Quaid, Sheena, Rabara, Ria, Radford, Alexandra, Radia, Kajal, Rajapaska, Durga, Rajeswaran, Thurkka, Ramos, Alberto San Francisco, Ramos Lopez, Fernando, Rampling, Tommy, Rand, Jade, Ratcliffe, Helen, Rawlinson, Tom, Rea, David, Rees, Byron, Reiné, Jesús, Resuello-Dauti, Mila, Reyes Pabon, Emilia, Ribiero, Carla M., Ricamara, Marivic, Richter, Alex, Ritchie, Neil, Ritchie, Adam J., Robbins, Alexander J., Roberts, Hannah, Robinson, Ryan E., Robinson, Hannah, Rocchetti, Talita T., Rocha, Beatriz Pinho, Roche, Sophie, Rollier, Christine, Rose, Louisa, Ross Russell, Amy L., Rossouw, Lindie, Royal, Simon, Rudiansyah, Indra, Ruiz, Sarah, Saich, Stephen, Sala, Claudia, Sale, Jessica, Salman, Ahmed M., Salvador, Natalia, Salvador, Stephannie, Sampaio, Milla, Samson, Annette D., Sanchez-Gonzalez, Amada, Sanders, Helen, Sanders, Katherine, Santos, Erika, Santos Guerra, Mayara F.S., Satti, Iman, Saunders, Jack E., Saunders, Caroline, Sayed, Aakifah, Schim van der Loeff, Ina, Schmid, Annina B., Schofield, Ella, Screaton, Gavin, Seddiqi, Samiullah, Segireddy, Rameswara R., Senger, Roberta, Serrano, Sonia, Shah, Rajiv, Shaik, Imam, Sharpe, Hannah E., Sharrocks, Katherine, Shaw, Robert, Shea, Adam, Shepherd, Amy, Shepherd, James G., Shiham, Farah, Sidhom, Emad, Silk, Sarah E., da Silva Moraes, Antonio Carlos, Silva-Junior, Gilberto, Silva-Reyes, Laura, Silveira, Anderson D., Silveira, Mariana B.V., Sinha, Jaisi, Skelly, Donal T., Smith, Daniel C., Smith, Nick, Smith, Holly E., Smith, David J., Smith, Catherine C., Soares, Airanuédida, Soares, Tiago, Solórzano, Carla, Sorio, Guilherme L., Sorley, Kim, Sosa-Rodriguez, Tiffany, Souza, Cinthia M.C.D.L., Souza, Bruno S.D.F., Souza, Alessandra R., Spencer, Alexandra J., Spina, Fernanda, Spoors, Louise, Stafford, Lizzie, Stamford, Imogen, Starinskij, Igor, Stein, Ricardo, Steven, Jill, Stockdale, Lisa, Stockwell, Lisa V., Strickland, Louise H., Stuart, Arabella C., Sturdy, Ann, Sutton, Natalina, Szigeti, Anna, Tahiri-Alaoui, Abdessamad, Tanner, Rachel, Taoushanis, Carol, Tarr, Alexander W., Taylor, Keja, Taylor, Ursula, Taylor, Iona Jennifer, Taylor, Justin, te Water Naude, Rebecca, Themistocleous, Yrene, Themistocleous, Andreas, Thomas, Merin, Thomas, Kelly, Thomas, Tonia M., Thombrayil, Asha, Thompson, Fawziyah, Thompson, Amber, Thompson, Kevin, Thompson, Ameeka, Thomson, Julia, Thornton-Jones, Viv, Tighe, Patrick J., Tinoco, Lygia Accioly, Tiongson, Gerlynn, Tladinyane, Bonolo, Tomasicchio, Michele, Tomic, Adriana, Tonks, Susan, Tran, Nguyen, Tree, Julia, Trillana, Gerry, Trinham, Charlotte, Trivett, Rose, Truby, Adam, Tsheko, Betty Lebogang, Turabi, Aadil, Turner, Richard, Turner, Cheryl, Ulaszewska, Marta, Underwood, Benjamin R., Varughese, Rachel, Verbart, Dennis, Verheul, Marije, Vichos, Iason, Vieira, Taiane, Waddington, Claire S., Walker, Laura, Wallis, Erica, Wand, Matthew, Warbick, Deborah, Wardell, Theresa, Warimwe, George, Warren, Sarah C., Watkins, Bridget, Watson, Ekaterina, Webb, Stewart, Webb-Bridges, Alice, Webster, Angela, Welch, Jessica, Wells, Jeanette, West, Alison, White, Caroline, White, Rachel, Williams, Paul, Williams, Rachel L., Winslow, Rebecca, Woodyer, Mark, Worth, Andrew T., Wright, Danny, Wroblewska, Marzena, Yao, Andy, Zimmer, Rafael, Zizi, Dalila and Zuidewind, Peter 2021. 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. Lancet 397 (10269) , pp. 99-111. 10.1016/S0140-6736(20)32661-1

[img]
Preview
PDF - Published Version
Available under License Creative Commons Attribution.

Download (340kB) | Preview

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 This analysis includes data from four ongoing blinded, randomised, controlled trials done across the UK, Brazil, and South Africa. Participants aged 18 years and older were randomly assigned (1:1) to ChAdOx1 nCoV-19 vaccine or control (meningococcal group A, C, W, and Y conjugate vaccine or saline). Participants in the ChAdOx1 nCoV-19 group received two doses containing 5 × 1010 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 Between April 23 and Nov 4, 2020, 23 848 participants were enrolled and 11 636 participants (7548 in the UK, 4088 in Brazil) were included in the interim primary efficacy analysis. In participants who received two standard doses, vaccine efficacy was 62·1% (95% CI 41·0–75·7; 27 [0·6%] of 4440 in the ChAdOx1 nCoV-19 group vs71 [1·6%] of 4455 in the control group) and in participants who received a low dose followed by a standard dose, efficacy was 90·0% (67·4–97·0; three [0·2%] of 1367 vs 30 [2·2%] of 1374; pinteraction=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.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Medicine
Additional Information: Open Access article under the CC BY 4.0 license
Publisher: Elsevier
ISSN: 0140-6736
Date of First Compliant Deposit: 11 December 2020
Date of Acceptance: 1 December 2020
Last Modified: 09 Mar 2021 13:04
URI: http://orca.cf.ac.uk/id/eprint/136956

Actions (repository staff only)

Edit Item Edit Item

Downloads

Downloads per month over past year

View more statistics