Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Randomized Controlled Trial
. 2021 Jan 9;397(10269):99-111.
doi: 10.1016/S0140-6736(20)32661-1. Epub 2020 Dec 8.

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  1 , Sue Ann Costa Clemens  2 , Shabir A Madhi  3 , Lily Y Weckx  4 , Pedro M Folegatti  5 , Parvinder K Aley  1 , Brian Angus  5 , Vicky L Baillie  6 , Shaun L Barnabas  7 , Qasim E Bhorat  8 , Sagida Bibi  1 , Carmen Briner  9 , Paola Cicconi  5 , Andrea M Collins  10 , Rachel Colin-Jones  1 , Clare L Cutland  6 , Thomas C Darton  11 , Keertan Dheda  12 , Christopher J A Duncan  13 , Katherine R W Emary  1 , Katie J Ewer  5 , Lee Fairlie  14 , Saul N Faust  15 , Shuo Feng  1 , Daniela M Ferreira  10 , Adam Finn  16 , Anna L Goodman  17 , Catherine M Green  18 , Christopher A Green  19 , Paul T Heath  20 , Catherine Hill  14 , Helen Hill  10 , Ian Hirsch  21 , Susanne H C Hodgson  5 , Alane Izu  22 , Susan Jackson  5 , Daniel Jenkin  5 , Carina C D Joe  5 , Simon Kerridge  1 , Anthonet Koen  22 , Gaurav Kwatra  14 , Rajeka Lazarus  23 , Alison M Lawrie  5 , Alice Lelliott  1 , Vincenzo Libri  24 , Patrick J Lillie  25 , Raburn Mallory  21 , Ana V A Mendes  26 , Eveline P Milan  27 , Angela M Minassian  5 , Alastair McGregor  28 , Hazel Morrison  5 , Yama F Mujadidi  1 , Anusha Nana  9 , Peter J O'Reilly  1 , Sherman D Padayachee  29 , Ana Pittella  30 , Emma Plested  1 , Katrina M Pollock  31 , Maheshi N Ramasamy  1 , Sarah Rhead  1 , Alexandre V Schwarzbold  32 , Nisha Singh  1 , Andrew Smith  33 , Rinn Song  34 , Matthew D Snape  1 , Eduardo Sprinz  35 , Rebecca K Sutherland  36 , Richard Tarrant  18 , Emma C Thomson  37 , M Estée Török  38 , Mark Toshner  39 , David P J Turner  40 , Johan Vekemans  21 , Tonya L Villafana  21 , Marion E E Watson  5 , Christopher J Williams  41 , Alexander D Douglas  5 , Adrian V S Hill  5 , Teresa Lambe  5 , Sarah C Gilbert  5 , Andrew J Pollard  42 ; Oxford COVID Vaccine Trial Group
Collaborators, Affiliations
Randomized Controlled Trial

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 et al. Lancet. .

Erratum in

  • Department of Error.
    [No authors listed] [No authors listed] Lancet. 2021 Jan 9;397(10269):98. doi: 10.1016/S0140-6736(20)32720-3. Lancet. 2021. PMID: 33422262 Free PMC article. No abstract available.

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.

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.

PubMed Disclaimer

Figures

Figure
Figure
Kaplan-Meier cumulative incidence of primary symptomatic, NAAT-positive COVID-19 Cumulative incidence of symptomatic COVID-19 after two doses (left) or after first standard dose in participants receiving only standard-dose vaccines (right). Grey shaded areas show the exclusion period after each dose in which cases were excluded from the analysis. Blue and red shaded areas show 95% CIs. LD/SD=low-dose prime plus standard-dose boost. MenACWY=meningococcal group A, C, W, and Y conjugate vaccine. NAAT=nucleic acid amplification test. SD/SD=two standard-dose vaccines given.
See this image and copyright information in PMC

Comment in

Similar articles

  • MOG encephalomyelitis after vaccination against severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2): case report and comprehensive review of the literature.
    Jarius S, Bieber N, Haas J, Wildemann B. Jarius S, et al. J Neurol. 2022 Oct;269(10):5198-5212. doi: 10.1007/s00415-022-11194-9. Epub 2022 Jun 23. J Neurol. 2022. PMID: 35737110 Free PMC article. Review.
  • Evaluation of the safety profile of COVID-19 vaccines: a rapid review.
    Wu Q, Dudley MZ, Chen X, Bai X, Dong K, Zhuang T, Salmon D, Yu H. Wu Q, et al. BMC Med. 2021 Jul 28;19(1):173. doi: 10.1186/s12916-021-02059-5. BMC Med. 2021. PMID: 34315454 Free PMC article. Review.
  • Efficacy of ChAdOx1 nCoV-19 (AZD1222) vaccine against SARS-CoV-2 variant of concern 202012/01 (B.1.1.7): an exploratory analysis of a randomised controlled trial.
    Emary KRW, Golubchik T, Aley PK, Ariani CV, Angus B, Bibi S, Blane B, Bonsall D, Cicconi P, Charlton S, Clutterbuck EA, Collins AM, Cox T, Darton TC, Dold C, Douglas AD, Duncan CJA, Ewer KJ, Flaxman AL, Faust SN, Ferreira DM, Feng S, Finn A, Folegatti PM, Fuskova M, Galiza E, Goodman AL, Green CM, Green CA, Greenland M, Hallis B, Heath PT, Hay J, Hill HC, Jenkin D, Kerridge S, Lazarus R, Libri V, Lillie PJ, Ludden C, Marchevsky NG, Minassian AM, McGregor AC, Mujadidi YF, Phillips DJ, Plested E, Pollock KM, Robinson H, Smith A, Song R, Snape MD, Sutherland RK, Thomson EC, Toshner M, Turner DPJ, Vekemans J, Villafana TL, Williams CJ, Hill AVS, Lambe T, Gilbert SC, Voysey M, Ramasamy MN, Pollard AJ; COVID-19 Genomics UK consortium; AMPHEUS Project; Oxford COVID-19 Vaccine Trial Group. Emary KRW, et al. Lancet. 2021 Apr 10;397(10282):1351-1362. doi: 10.1016/S0140-6736(21)00628-0. Epub 2021 Mar 30. Lancet. 2021. PMID: 33798499 Free PMC article. Clinical Trial.
  • Single-dose administration and the influence of the timing of the booster dose on immunogenicity and efficacy of ChAdOx1 nCoV-19 (AZD1222) vaccine: a pooled analysis of four randomised trials.
    Voysey M, Costa Clemens SA, Madhi SA, Weckx LY, Folegatti PM, Aley PK, Angus B, Baillie VL, Barnabas SL, Bhorat QE, Bibi S, Briner C, Cicconi P, Clutterbuck EA, Collins AM, Cutland CL, Darton TC, Dheda K, Dold C, Duncan CJA, Emary KRW, Ewer KJ, Flaxman A, Fairlie L, Faust SN, Feng S, Ferreira DM, Finn A, Galiza E, Goodman AL, Green CM, Green CA, Greenland M, Hill C, Hill HC, Hirsch I, Izu A, Jenkin D, Joe CCD, Kerridge S, Koen A, Kwatra G, Lazarus R, Libri V, Lillie PJ, Marchevsky NG, Marshall RP, Mendes AVA, Milan EP, Minassian AM, McGregor A, Mujadidi YF, Nana A, Padayachee SD, Phillips DJ, Pittella A, Plested E, Pollock KM, Ramasamy MN, Ritchie AJ, Robinson H, Schwarzbold AV, Smith A, Song R, Snape MD, Sprinz E, Sutherland RK, Thomson EC, Török ME, Toshner M, Turner DPJ, Vekemans J, Villafana TL, White T, Williams CJ, Douglas AD, Hill AVS, Lambe T, Gilbert SC, Pollard AJ; Oxford COVID Vaccine Trial Group. Voysey M, et al. Lancet. 2021 Mar 6;397(10277):881-891. doi: 10.1016/S0140-6736(21)00432-3. Epub 2021 Feb 19. Lancet. 2021. PMID: 33617777 Free PMC article.
  • Safety and immunogenicity of ChAdOx1 nCoV-19 vaccine administered in a prime-boost regimen in young and old adults (COV002): a single-blind, randomised, controlled, phase 2/3 trial.
    Ramasamy MN, Minassian AM, Ewer KJ, Flaxman AL, Folegatti PM, Owens DR, Voysey M, Aley PK, Angus B, Babbage G, Belij-Rammerstorfer S, Berry L, Bibi S, Bittaye M, Cathie K, Chappell H, Charlton S, Cicconi P, Clutterbuck EA, Colin-Jones R, Dold C, Emary KRW, Fedosyuk S, Fuskova M, Gbesemete D, Green C, Hallis B, Hou MM, Jenkin D, Joe CCD, Kelly EJ, Kerridge S, Lawrie AM, Lelliott A, Lwin MN, Makinson R, Marchevsky NG, Mujadidi Y, Munro APS, Pacurar M, Plested E, Rand J, Rawlinson T, Rhead S, Robinson H, Ritchie AJ, Ross-Russell AL, Saich S, Singh N, Smith CC, Snape MD, Song R, Tarrant R, Themistocleous Y, Thomas KM, Villafana TL, Warren SC, Watson MEE, Douglas AD, Hill AVS, Lambe T, Gilbert SC, Faust SN, Pollard AJ; Oxford COVID Vaccine Trial Group. Ramasamy MN, et al. Lancet. 2021 Dec 19;396(10267):1979-1993. doi: 10.1016/S0140-6736(20)32466-1. Epub 2020 Nov 19. Lancet. 2021. PMID: 33220855 Free PMC article. Clinical Trial.
See all similar articles

Cited by

See all "Cited by" articles

References

    1. WHO WHO coronavirus disease (COVID-19) dashboard. 2020. https://covid19.who.int
    1. Zhou F, Yu T, Du R. Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study. Lancet. 2020;395:1054–1062. - PMC - PubMed
    1. Stringhini S, Wisniak A, Piumatti G. Seroprevalence of anti-SARS-CoV-2 IgG antibodies in Geneva, Switzerland (SEROCoV-POP): a population-based study. Lancet. 2020;396:313–319. - PMC - PubMed
    1. WHO DRAFT landscape of COVID-19 candidate vaccines—20 March 2020. 2020. https://www.who.int/blueprint/priority-diseases/key-action/novel-coronav...
    1. Folegatti PM, Ewer KJ, Aley PK. Safety and immunogenicity of the ChAdOx1 nCoV-19 vaccine against SARS-CoV-2: a preliminary report of a phase 1/2, single-blind, randomised controlled trial. Lancet. 2020;396:467–478. - PMC - PubMed

Publication types

Associated data

-