36473651 2022 12 15 2024 06 05
1469-493X 12 12 2022 Dec 07 The Cochrane database of systematic reviews Cochrane Database Syst Rev Efficacy and safety of COVID-19 vaccines. CD015477 CD015477 CD015477 10.1002/14651858.CD015477 Different forms of vaccines have been developed to prevent the SARS-CoV-2 virus and subsequent COVID-19 disease. Several are in widespread use globally.  OBJECTIVES: To assess the efficacy and safety of COVID-19 vaccines (as a full primary vaccination series or a booster dose) against SARS-CoV-2. We searched the Cochrane COVID-19 Study Register and the COVID-19 L·OVE platform (last search date 5 November 2021). We also searched the WHO International Clinical Trials Registry Platform, regulatory agency websites, and Retraction Watch. We included randomized controlled trials (RCTs) comparing COVID-19 vaccines to placebo, no vaccine, other active vaccines, or other vaccine schedules. We used standard Cochrane methods. We used GRADE to assess the certainty of evidence for all except immunogenicity outcomes.  We synthesized data for each vaccine separately and presented summary effect estimates with 95% confidence intervals (CIs).  MAIN RESULTS: We included and analyzed 41 RCTs assessing 12 different vaccines, including homologous and heterologous vaccine schedules and the effect of booster doses. Thirty-two RCTs were multicentre and five were multinational. The sample sizes of RCTs were 60 to 44,325 participants. Participants were aged: 18 years or older in 36 RCTs; 12 years or older in one RCT; 12 to 17 years in two RCTs; and three to 17 years in two RCTs. Twenty-nine RCTs provided results for individuals aged over 60 years, and three RCTs included immunocompromized patients. No trials included pregnant women. Sixteen RCTs had two-month follow-up or less, 20 RCTs had two to six months, and five RCTs had greater than six to 12 months or less. Eighteen reports were based on preplanned interim analyses. Overall risk of bias was low for all outcomes in eight RCTs, while 33 had concerns for at least one outcome. We identified 343 registered RCTs with results not yet available.  This abstract reports results for the critical outcomes of confirmed symptomatic COVID-19, severe and critical COVID-19, and serious adverse events only for the 10 WHO-approved vaccines. For remaining outcomes and vaccines, see main text. The evidence for mortality was generally sparse and of low or very low certainty for all WHO-approved vaccines, except AD26.COV2.S (Janssen), which probably reduces the risk of all-cause mortality (risk ratio (RR) 0.25, 95% CI 0.09 to 0.67; 1 RCT, 43,783 participants; high-certainty evidence). Confirmed symptomatic COVID-19 High-certainty evidence found that BNT162b2 (BioNtech/Fosun Pharma/Pfizer), mRNA-1273 (ModernaTx), ChAdOx1 (Oxford/AstraZeneca), Ad26.COV2.S, BBIBP-CorV (Sinopharm-Beijing), and BBV152 (Bharat Biotect) reduce the incidence of symptomatic COVID-19 compared to placebo (vaccine efficacy (VE): BNT162b2: 97.84%, 95% CI 44.25% to 99.92%; 2 RCTs, 44,077 participants; mRNA-1273: 93.20%, 95% CI 91.06% to 94.83%; 2 RCTs, 31,632 participants; ChAdOx1: 70.23%, 95% CI 62.10% to 76.62%; 2 RCTs, 43,390 participants; Ad26.COV2.S: 66.90%, 95% CI 59.10% to 73.40%; 1 RCT, 39,058 participants; BBIBP-CorV: 78.10%, 95% CI 64.80% to 86.30%; 1 RCT, 25,463 participants; BBV152: 77.80%, 95% CI 65.20% to 86.40%; 1 RCT, 16,973 participants). Moderate-certainty evidence found that NVX-CoV2373 (Novavax) probably reduces the incidence of symptomatic COVID-19 compared to placebo (VE 82.91%, 95% CI 50.49% to 94.10%; 3 RCTs, 42,175 participants). There is low-certainty evidence for CoronaVac (Sinovac) for this outcome (VE 69.81%, 95% CI 12.27% to 89.61%; 2 RCTs, 19,852 participants). Severe or critical COVID-19 High-certainty evidence found that BNT162b2, mRNA-1273, Ad26.COV2.S, and BBV152 result in a large reduction in incidence of severe or critical disease due to COVID-19 compared to placebo (VE: BNT162b2: 95.70%, 95% CI 73.90% to 99.90%; 1 RCT, 46,077 participants; mRNA-1273: 98.20%, 95% CI 92.80% to 99.60%; 1 RCT, 28,451 participants; AD26.COV2.S: 76.30%, 95% CI 57.90% to 87.50%; 1 RCT, 39,058 participants; BBV152: 93.40%, 95% CI 57.10% to 99.80%; 1 RCT, 16,976 participants). Moderate-certainty evidence found that NVX-CoV2373 probably reduces the incidence of severe or critical COVID-19 (VE 100.00%, 95% CI 86.99% to 100.00%; 1 RCT, 25,452 participants). Two trials reported high efficacy of CoronaVac for severe or critical disease with wide CIs, but these results could not be pooled. Serious adverse events (SAEs) mRNA-1273, ChAdOx1 (Oxford-AstraZeneca)/SII-ChAdOx1 (Serum Institute of India), Ad26.COV2.S, and BBV152 probably result in little or no difference in SAEs compared to placebo (RR: mRNA-1273: 0.92, 95% CI 0.78 to 1.08; 2 RCTs, 34,072 participants; ChAdOx1/SII-ChAdOx1: 0.88, 95% CI 0.72 to 1.07; 7 RCTs, 58,182 participants; Ad26.COV2.S: 0.92, 95% CI 0.69 to 1.22; 1 RCT, 43,783 participants); BBV152: 0.65, 95% CI 0.43 to 0.97; 1 RCT, 25,928 participants). In each of these, the likely absolute difference in effects was fewer than 5/1000 participants. Evidence for SAEs is uncertain for BNT162b2, CoronaVac, BBIBP-CorV, and NVX-CoV2373 compared to placebo (RR: BNT162b2: 1.30, 95% CI 0.55 to 3.07; 2 RCTs, 46,107 participants; CoronaVac: 0.97, 95% CI 0.62 to 1.51; 4 RCTs, 23,139 participants; BBIBP-CorV: 0.76, 95% CI 0.54 to 1.06; 1 RCT, 26,924 participants; NVX-CoV2373: 0.92, 95% CI 0.74 to 1.14; 4 RCTs, 38,802 participants). For the evaluation of heterologous schedules, booster doses, and efficacy against variants of concern, see main text of review. Compared to placebo, most vaccines reduce, or likely reduce, the proportion of participants with confirmed symptomatic COVID-19, and for some, there is high-certainty evidence that they reduce severe or critical disease. There is probably little or no difference between most vaccines and placebo for serious adverse events. Over 300 registered RCTs are evaluating the efficacy of COVID-19 vaccines, and this review is updated regularly on the COVID-NMA platform (covid-nma.com). Implications for practice Due to the trial exclusions, these results cannot be generalized to pregnant women, individuals with a history of SARS-CoV-2 infection, or immunocompromized people. Most trials had a short follow-up and were conducted before the emergence of variants of concern. Implications for research Future research should evaluate the long-term effect of vaccines, compare different vaccines and vaccine schedules, assess vaccine efficacy and safety in specific populations, and include outcomes such as preventing long COVID-19. Ongoing evaluation of vaccine efficacy and effectiveness against emerging variants of concern is also vital. Copyright © 2022 The Authors. Cochrane Database of Systematic Reviews published by John Wiley & Sons, Ltd. on behalf of The Cochrane Collaboration. Graña Carolina C Cochrane France, Paris, France. Centre of Research in Epidemiology and Statistics (CRESS), INSERM, INRAE, Université de Paris, Paris, France. Ghosn Lina L Cochrane France, Paris, France. Centre of Research in Epidemiology and Statistics (CRESS), INSERM, INRAE, Université de Paris, Paris, France. Evrenoglou Theodoros T Centre of Research in Epidemiology and Statistics (CRESS), INSERM, INRAE, Université de Paris, Paris, France. Jarde Alexander A Cochrane France, Paris, France. Centre of Research in Epidemiology and Statistics (CRESS), INSERM, INRAE, Université de Paris, Paris, France. Minozzi Silvia S Cochrane Review Group on Drugs and Alcohol, Rome, Italy. Bergman Hanna H Cochrane Response, Cochrane, London, UK. Buckley Brian S BS Cochrane Response, Cochrane, London, UK. Probyn Katrin K Cochrane Response, Cochrane, London, UK. Villanueva Gemma G Cochrane Response, Cochrane, London, UK. Henschke Nicholas N Cochrane Response, Cochrane, London, UK. Bonnet Hillary H Cochrane France, Paris, France. Centre of Research in Epidemiology and Statistics (CRESS), INSERM, INRAE, Université de Paris, Paris, France. Assi Rouba R Cochrane France, Paris, France. Centre of Research in Epidemiology and Statistics (CRESS), INSERM, INRAE, Université de Paris, Paris, France. Menon Sonia S Cochrane France, Paris, France. Marti Melanie M Department of Immunization, Vaccines and Biologicals, World Health Organization, Geneva, Switzerland. Devane Declan D Evidence Synthesis Ireland, Cochrane Ireland and HRB-Trials Methodology Research Network, National University of Ireland, Galway, Ireland. Mallon Patrick P UCD Centre for Experimental Pathogen Host Research and UCD School of Medicine, University College Dublin, Dublin, Ireland. Lelievre Jean-Daniel JD Department of Clinical Immunology and Infectious Diseases, Henri Mondor Hospital, Vaccine Research Institute, Université Paris Est Créteil, Paris, France. Askie Lisa M LM Quality Assurance Norms and Standards Department, World Health Organization, Geneva, Switzerland. Kredo Tamara T Cochrane South Africa, South African Medical Research Council, Cape Town, South Africa. Ferrand Gabriel G Cochrane France, Paris, France. Davidson Mauricia M Cochrane France, Paris, France. Centre of Research in Epidemiology and Statistics (CRESS), INSERM, INRAE, Université de Paris, Paris, France. Riveros Carolina C Cochrane France, Paris, France. Centre of Research in Epidemiology and Statistics (CRESS), INSERM, INRAE, Université de Paris, Paris, France. Tovey David D Cochrane France, Paris, France. Meerpohl Joerg J JJ Institute for Evidence in Medicine, Medical Center & Faculty of Medicine, University of Freiburg, Freiburg, Germany. Cochrane Germany, Cochrane Germany Foundation, Freiburg, Germany. Grasselli Giacomo G Department of Anesthesia, Intensive Care and Emergency, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Department of Pathophysiology and Transplantation, University of Milan, Milan, Italy. Rada Gabriel G Epistemonikos Foundation, Santiago, Chile. UC Evidence Center, Cochrane Chile Associated Center, Pontificia Universidad Católica de Chile, Santiago, Chile. Hróbjartsson Asbjørn A Centre for Evidence Based Medicine Odense (CEBMO) and Cochrane Denmark, University of Southern Denmark, Odense, Denmark. Open Patient data Explorative Network (OPEN), Odense University Hospital, Odense, Denmark. Ravaud Philippe P Cochrane France, Paris, France. Centre of Research in Epidemiology and Statistics (CRESS), INSERM, INRAE, Université de Paris, Paris, France. Chaimani Anna A Cochrane France, Paris, France. Centre of Research in Epidemiology and Statistics (CRESS), INSERM, INRAE, Université de Paris, Paris, France. Boutron Isabelle I Cochrane France, Paris, France. Centre of Research in Epidemiology and Statistics (CRESS), INSERM, INRAE, Université de Paris, Paris, France. eng 001 WHO_ World Health Organization International Journal Article Review Systematic Review 2022 12 07
England Cochrane Database Syst Rev 100909747 1361-6137 0 sinovac COVID-19 vaccine 0 BIBP COVID-19 vaccine 76JZE5DSN6 BBV152 COVID-19 vaccine EPK39PL4R4 2019-nCoV Vaccine mRNA-1273 IM Humans Middle Aged Aged Adolescent 2019-nCoV Vaccine mRNA-1273 COVID-19 prevention & control SARS-CoV-2 Carolina Graña: none known. Lina Ghosn: none known. Theodoros Evrenoglou: none known. Alexander Jarde: none known. Silvia Minozzi: no relevant interests; Joint Co‐ordinating Editor and Method editor of the Drugs and Alcohol Group. Hanna Bergman: Cochrane Response – consultant; WHO – grant/contract (Cochrane Response was commissioned by the WHO to perform review tasks that contribute to this publication). . Brian Buckley: none known. . Katrin Probyn: Cochrane Response – consultant; WHO – consultant (Cochrane Response was commissioned to perform review tasks that contribute to this publication). . Gemma Villanueva: Cochrane Response – employment (Cochrane Response has been commissioned by WHO to perform parts of this systematic review). . Nicholas Henschke: Cochrane Response – consultant; WHO – consultant (Cochrane Response was commissioned by the WHO to perform review tasks that contributed to this publication). . Hillary Bonnet: none known. Rouba Assi: none known. Sonia Menon: P95 – consultant. Melanie Marti: no relevant interests; Medical Officer at WHO. Declan Devane: Health Research Board (HRB) – grant/contract; registered nurse and registered midwife but no longer in clinical practice; Editor, Cochrane Pregnancy and Childbirth Group. Patrick Mallon: AstraZeneca – Advisory Board; spoken of vaccine effectiveness to media (print, online, and live); works as a consultant in a hospital that provides vaccinations; employed by St Vincent's University Hospital. Jean‐Daniel Lelievre: no relevant interests; published numerous interviews in the national press on the subject of COVID vaccination; Head of the Department of Infectious Diseases and Clinical Immunology CHU Henri Mondor APHP, Créteil; WHO (IVRI‐AC): expert Vaccelarate (European project on COVID19 Vaccine): head of WP; involved with COVICOMPARE P et M Studies (APHP, INSERM) (public fundings). . Lisa Askie: no relevant interests; Co‐convenor, Cochrane Prospective Meta‐analysis Methods Group. Tamara Kredo: no relevant interests; Medical Officer in an Infectious Diseases Clinic at Tygerberg Hospital, Stellenbosch University. Gabriel Ferrand: none known. Mauricia Davidson: none known. Carolina Riveros: no relevant interests; works as an epidemiologist. David Tovey: no relevant interests; Emeritus Editor in Chief, Feedback Editors for 2 Cochrane review groups. Joerg J Meerpohl: no relevant interests; member of the German Standing Vaccination Committee (STIKO). Giacomo Grasselli: Pfizer – speaking engagement. Gabriel Rada: none known. Asbjørn Hróbjartsson: no relevant interests; Cochrane Methodology Review Group Editor. Philippe Ravaud: no relevant interests; involved with Mariette CORIMUNO‐19 Collaborative 2021, the Ministry of Health, Programme Hospitalier de Recherche Clinique, Foundation for Medical Research, and AP‐HP Foundation. Anna Chaimani: none known. Isabelle Boutron: no relevant interests; member of Cochrane Editorial Board. 2022 12 6 19 26 2022 12 7 6 0 2022 12 15 6 0 2022 12 7 epublish 36473651 PMC9726273 10.1002/14651858.CD015477 References to studies included in this review Ali 2021 {published data only} Ali K, Berman G, Zhou H, Deng W, Faughnan V, Coronado-Voges M, et al. Evaluation of mRNA-1273 SARS-CoV-2 vaccine in adolescents. New England Journal of Medicine 2021;385(24):2241-51. PMC8385554 34379915 Al Kaabi 2021 {published data only} Al Kaabi N, Zhang Y, Xia S, Yang Y, Al Qahtani MM, Abdulrazzaq N, et al. Effect of 2 inactivated SARS-CoV-2 vaccines on symptomatic COVID-19 infection in adults: a randomized clinical trial. JAMA 2021;326(1):35-45. PMC8156175 34037666 Asano 2022 {published data only} Asano M, Okada H, Itoh Y, Hirata H, Ishikawa K, Yoshida E, et al. Immunogenicity and safety of AZD1222 (ChAdOx1 nCoV-19) against SARS-CoV-2 in Japan: a double-blind, randomized controlled phase 1/2 trial. International Journal of Infectious Diseases 2022;114:165-74. PMC8531242 34688944 Bonelli 2021 {published data only} Bonelli M, Mrak D, Tobudic S, Sieghart D, Koblischke M, Mandl P, et al. Additional heterologous versus homologous booster vaccination in immunosuppressed patients without SARS-CoV-2 antibody seroconversion after primary mRNA vaccination: a randomized controlled trial. medRxiv 2021 [Preprint]. [DOI: 10.1101/2021.09.05.21263125] 10.1101/2021.09.05.21263125 35027397 Bueno 2021 {published data only} Bueno SM, Abarca K, González PA, Gálvez NM, Soto JA, Duarte LF, et al. Interim report: safety and immunogenicity of an inactivated vaccine against SARS-CoV-2 in healthy Chilean adults in a phase 3 clinical trial. medRxiv 2021 [Preprint]. [DOI: 10.1101/2021.03.31.21254494] 10.1101/2021.03.31.21254494 Bueno SM, Abarca K, González PA, Gálvez NM, Soto JA, Duarte LF, et al. Safety and immunogenicity of an inactivated SARS-CoV-2 vaccine in a subgroup of healthy adults in Chile. Clinical Infectious Diseases 2021 Sep 19 [Epub ahead of print]. [DOI: 10.1093/cid/ciab823] 10.1093/cid/ciab823 PMC9402626 34537835 Clemens 2021 {published data only} Clemens SA, Folegatti PM, Emary KR, Weckx LY, Ratcliff J, Bibi S, et al. Efficacy of ChAdOx1 nCoV-19 (AZD1222) vaccine against SARS-CoV-2 lineages circulating in Brazil. Nature Communications 2021;12(1):5861. PMC8494913 34615860 Dunkle 2021 {published data only} Dunkle LM, Kotloff KL, Gay CL, Áñez G, Adelglass JM, Barrat Hernández AQ, et al. Efficacy and safety of NVX-CoV2373 in adults in the United States and Mexico. medRxiv 2021 [Preprint]. [DOI: 10.1101/2021.10.05.21264567] 10.1101/2021.10.05.21264567 PMC8693692 34910859 Ella 2021a {published data only} Ella R, Vadrevu KM, Jogdand H, Prasad S, Reddy S, Sarangi V, et al. A Phase 1: safety and immunogenicity trial of an inactivated SARS-CoV-2 vaccine-BBV152. medRxiv 2020 [Preprint]. [DOI: 10.1101/2020.12.11.20210419] 10.1101/2020.12.11.20210419 PMC7825810 33485468 Ella R, Vadrevu KM, Jogdand H, Prasad S, Reddy S, Sarangi V, et al. Safety and immunogenicity of an inactivated SARS-CoV-2 vaccine, BBV152: a double-blind, randomized, phase 1 trial. Lancet Infectious Diseases 2021;21(5):637-46. PMC7825810 33485468 Ella 2021b {published data only} Ella R, Reddy S, Blackwelder W, Potdar V, Yadav P, Sarangi V, et al. Efficacy, safety, and lot to lot immunogenicity of an inactivated SARS-CoV-2 vaccine (BBV152): a double-blind, randomized, controlled phase 3 trial. medRxiv 2021 [Preprint]. [DOI: 10.1101/2021.06.30.21259439] 10.1101/2021.06.30.21259439 PMC8584828 34774196 El Sahly 2021 {published data only} Baden LR, El Sahly HM, Essink B, Kotloff K, Frey S, Novak R, et al. Efficacy and safety of the mRNA-1273 SARS-CoV-2 vaccine. New England Journal of Medicine 2021;384(5):403-16. PMC7787219 33378609 El Sahly HM, Baden LR, Essink B, Doblecki-Lewis S, Martin JM, Anderson EJ, et al. Efficacy of the mRNA-1273 SARS-CoV-2 vaccine at completion of blinded phase. New England Journal of Medicine 2021;385(19):1774-85. PMC8482810 34551225 Food and Drug Administration. Vaccines and Related Biological Products Advisory Committee Meeting; December 17, 2020; FDA Briefing Document: Moderna COVID-19 vaccine. www.fda.gov/media/144434/download (accessed prior to 1 November 2022). Emary 2021 {published data only} Emary KR, Golubchik T, Aley PK, Ariani CV, Angus B, Bibi S, et al. 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 randomized controlled trial. Lancet 2021;397(10282):1351-62. PMC8009612 33798499 Fadlyana 2021 {published data only} Fadlyana E, Rusmil K, Tarigan R, Rahmadi AR, Prodjosoewojo S, Sofiatin Y, et al. A phase III, observer-blind, randomized, placebo-controlled study of the efficacy, safety, and immunogenicity of SARS-CoV-2 inactivated vaccine in healthy adults aged 18–59 years: an interim analysis in Indonesia. Vaccine 2021;39(44):6520-8. PMC8461222 34620531 Falsey 2021 {published data only} Falsey AR, Sobieszczyk ME, Hirsch I, Sproule S, Robb ML, Corey L, et al. Phase 3 safety and efficacy of AZD1222 (ChAdOx1 nCoV-19) Covid-19 vaccine. New England Journal of Medicine 2021;385(25):2348-60. PMC8522798 34587382 Formica 2021 {published data only} Formica N, Mallory R, Albert G, Robinson M, Plested JS, Cho I, et al. Different dose regimens of a SARS-CoV-2 recombinant spike protein vaccine (NVX-CoV2373) in younger and older adults: a phase 2 randomized placebo-controlled trial. PLOS Medicine 2021;18(10):e1003769. PMC8486115 34597298 Formica N, Mallory R, Albert G, Robinson M, Plested JS, Cho I, et al. Evaluation of a SARS-CoV-2 vaccine NVX-CoV2373 in younger and older adults. medRxiv 2021 [Preprint]. [DOI: 10.1101/2021.02.26.21252482] 10.1101/2021.02.26.21252482 PMC8486115 34597298 Frenck 2021 {published data only} Frenck RW Jr, Klein NP, Kitchin N, Gurtman A, Absalon J, Lockhart S, et al. Safety, immunogenicity, and efficacy of the BNT162b2 Covid-19 vaccine in adolescents. New England Journal of Medicine 2021;385(3):239-50. PMC8174030 34043894 Guo 2021 {published data only} Guo W, Duan K, Zhang Y, Yuan Z, Zhang YB, Wang Z, et al. Safety and immunogenicity of an inactivated SARS-CoV-2 vaccine in healthy adults aged 18 years or older: a randomized, double-blind, placebo-controlled, phase 1/2 trial. eClinicalMedicine 2021;38:101010. PMC8260504 34250456 Hall 2021 {published data only} Hall VG, Ferreira VH, Ku T, Ierullo M, Majchrzak-Kita B, Chaparro C, et al. Randomized trial of a third dose of mRNA-1273 vaccine in transplant recipients. New England Journal of Medicine 2021;385(13):1244-6. PMC8385563 34379917 Han 2021 {published data only} Han B, Song Y, Li C, Yang W, Ma Q, Jiang Z, et al. Safety, tolerability, and immunogenicity of an inactivated SARS-CoV-2 vaccine (CoronaVac) in healthy children and adolescents: a double-blind, randomized, controlled, phase 1/2 clinical trial. Lancet Infectious Diseases 2021;21(12):1645-53. PMC8238449 34197764 Heath 2021 {published data only} Heath PT, Galiza EP, Baxter DN, Boffito M, Browne D, Burns F, et al. Safety and efficacy of NVX-CoV2373 Covid-19 vaccine. New England Journal of Medicine 2021;385(13):1172-83. PMC8262625 34192426 Heath PT, Galiza EP, Baxter DN, Boffito M, Browne D, Burns F, et al . Efficacy of the NVX-CoV2373 Covid-19 vaccine against the B. 1.1.7 variant. medRxiv 2021 [Preprint]. Keech 2020 {published data only} Keech C, Albert G, Cho I, Robertson A, Reed P, Neal S, et al. Phase 1-2 trial of a SARS-CoV-2 recombinant spike protein nanoparticle vaccine. New England Journal of Medicine  2020;383:2320-32. PMC7494251 32877576 Kremsner 2021 {published data only} Kremsner PG, Ahuad Guerrero RA, Arana-Arri E, Aroca Martinez GJ, Bonten M, Chandler R, et al. Efficacy and safety of the CVnCoV SARS-CoV-2 mRNA vaccine candidate: results from Herald, a phase 2b/3, randomized, observer-blinded, placebo-controlled clinical trial in ten countries in Europe and Latin America. SSRN 2021 [Preprint]. [DOI: 10.2139/ssrn.3911826] 10.2139/ssrn.3911826 PMC8610426 34826381 Kulkarni 2021 {published data only} Kulkarni PS, Padmapriyadarsini C, Vekemans J, Bavdekar A, Gupta M, Kulkarni P, et al. A phase 2/3, observer-blind, randomized, controlled study to assess the safety and immunogenicity of SII-ChAdOx1 nCOV-19 (COVID-19 vaccine) in adults in India. eClinicalMedicine 2021;42:101218. PMC8629682 34870133 Li 2021a {published data only} Li J, Hou L, Guo X, Jin P, Wu S, Zhu J, et al. Heterologous prime-boost immunization with CoronaVac and Convidecia. medRxiv 2021 [Preprint]. [DOI: 10.1101/2021.09.03.21263062] 10.1101/2021.09.03.21263062 Liu 2021 {published data only} Liu X, Shaw RH, Stuart AS, Greenland M, Aley PK, Andrews NJ, et al. Safety and immunogenicity of heterologous versus homologous prime-boost schedules with an adenoviral vectored and mRNA COVID-19 vaccine (Com-COV): a single-blind, randomized, non-inferiority trial. Lancet 2021;398(10303):856-69. PMC8346248 34370971 Liu X, Shaw RH, Stuart AS, Greenland M, Aley PK, Andrews NJ, et al. Safety and immunogenicity report from the Com-COV Study – a single-blind randomized non-inferiority trial comparing heterologous and homologous prime-boost schedules with an adenoviral vectored and mRNA COVID-19 vaccine. SSRN 2021 [Preprint]. [DOI: 10.2139/ssrn.3874014] 10.2139/ssrn.3874014 PMC8346248 34370971 Logunov 2021 {published data only} Logunov DY, Dolzhikova IV, Shcheblyakov DV, Tukhvatulin AI, Zubkova OV, Dzharullaeva AS, et al. Safety and efficacy of an rAd26 and rAd5 vector-based heterologous prime-boost COVID-19 vaccine: an interim analysis of a randomized controlled phase 3 trial in Russia. Lancet 2021;397(10275):671-81. PMC7852454 33545094 Madhi 2021a {published data only} Madhi SA, Koen AL, Izu A, Fairlie L, Cutland CL, Baillie V, et al. Safety and immunogenicity of the ChAdOx1 nCoV-19 (AZD1222) vaccine against SARS-CoV-2 in people living with and without HIV in South Africa: an interim analysis of a randomized, double-blind, placebo-controlled, phase 1B/2A trial. Lancet HIV 2021;8(9):e568-80. PMC8372504 34416193 Madhi 2021b {published data only} Madhi SA, Baillie V, Cutland CL, Voysey M, Koen AL, Fairlie L, et al. Efficacy of the ChAdOx1 nCoV-19 Covid-19 vaccine against the B.1.351 variant. New England Journal of Medicine 2021;384(20):1885-98. PMC7993410 33725432 Mok 2021 {published data only} Mok C, Cheng S, Chen C, Yiu K, Chan TO, Lai KC, et al. A RCT of a third dose CoronaVac or BNT162b2 vaccine in adults with two doses of CoronaVac. medRxiv 2021 [Preprint]. [DOI: 10.1101/2021.11.02.21265843] 10.1101/2021.11.02.21265843 Palacios 2020 {published data only} Palacios R, Patiño EG, Oliveira Piorelli R, Conde MT, Batista AP, Zeng G, et al. Double-blind, randomized, placebo-controlled phase III clinical trial to evaluate the efficacy and safety of treating healthcare professionals with the adsorbed COVID-19 (inactivated) vaccine manufactured by Sinovac – PROFISCOV: a structured summary of a study protocol for a randomized controlled trial. Trials 2020;21(1):853. PMC7558252 33059771 Sablerolles 2021 {published data only} Sablerolles RS, Rietdijk WJ, Goorhuis A, Postma DF, Visser LG, Geers D, et al. Immunogenicity and reactogenicity of booster vaccinations after Ad26.COV2.S priming. medRxiv 2021 [Preprint]. [DOI: 10.1101/2021.10.18.21264979] 10.1101/2021.10.18.21264979 Sadoff 2021a {published data only} Food and Drug Administration. Vaccines and related biological products Advisory Committee Meeting; February 26, 2021; FDA briefing document: Janssen Ad26.COV2.S vaccine for the prevention of COVID-19. www.fda.gov/media/146217/download (accessed prior to 1 November 2022). Sadoff J, Le Gars M, Shukarev G, Heerwegh D, Truyers C, Groot AM, et al. Interim results of a Phase 1-2a trial of Ad26.COV2.S Covid-19 vaccine. New England Journal of Medicine 2021;384(19):1824-35. PMC7821985 33440088 Sadoff J, Le Gars M, Shukarev G, Heerwegh D, Truyers C, Groot AM, et al. Safety and immunogenicity of the Ad26.COV2.S COVID-19 vaccine candidate: interim results of a phase 1/2a, double-blind, randomized, placebo-controlled trial. medRxiv 2020 [Preprint]. [DOI: 10.1101/2020.09.23.20199604] 10.1101/2020.09.23.20199604 Sadoff 2021b {published data only} Sadoff J, Gray G, Vandebosch A, Cárdenas V, Shukarev G, Grinsztejn B, et al. Safety and efficacy of single-dose Ad26.COV2.S vaccine against Covid-19. New England Journal of Medicine 2021;384(23):2187-201. PMC8220996 33882225 Shinde 2021 {published data only} Shinde V, Bhikha S, Hoosain Z, Archary M, Bhorat Q, Fairlie L, et al. Efficacy of NVX-CoV2373 Covid-19 vaccine against the B.1.351 variant. New England Journal of Medicine 2021;384(20):1899-909. PMC8091623 33951374 Shinde V, Bhikha S, Hoosain Z, Archary M, Bhorat Q, Fairlie L, et al. Preliminary efficacy of the NVX-CoV2373 Covid-19 vaccine against the B.1.351 variant. medRxiv 2021 [Preprint]. [DOI: 10.1101/2021.02.25.21252477] 10.1101/2021.02.25.21252477 PMC8091623 33951374 Tanriover 2021 {published data only} Tanriover MD, Doğanay HL, Akova M, Güner HR, Azap A, Akhan S, et al. Efficacy and safety of an inactivated whole-virion SARS-CoV-2 vaccine (CoronaVac): interim results of a double-blind, randomized, placebo-controlled, phase 3 trial in Turkey. Lancet 2021;398(10296):213-22. PMC8266301 34246358 Thomas 2021 {published data only} Food and Drug Administration. Vaccines and related biological products Advisory Committee Meeting; December 10, 2020; FDA briefing document: Pfizer-BioNTech COVID-19 vaccine. www.fda.gov/media/144245/download (accessed prior to 1 November 2022). Polack FP, Thomas SJ, Kitchin N, Absalon J, Gurtman A, Lockhart S, et al. Safety and efficacy of the BNT162b2 mRNA Covid-19 vaccine. New England Journal of Medicine 2020;383(27):2603-15. PMC7745181 33301246 Thomas SJ, Moreira ED Jr, Kitchin N, Absalon J, Gurtman A, Lockhart S, et al. Safety and efficacy of the BNT162b2 mRNA Covid-19 vaccine through 6 months. New England Journal of Medicine 2021;385(19):1761-773. PMC8461570 34525277 Thomas SJ, Moreira ED Jr, Kitchin N, Absalon J, Gurtman A, Lockhart S, et al. Six month safety and efficacy of the BNT162b2 mRNA COVID-19 vaccine. medRxiv 2021 [Preprint]. [DOI: 10.1101/2021.07.28.21261159] 10.1101/2021.07.28.21261159 PMC8461570 34525277 Toledo‐Romani 2021 {published data only} Toledo-Romani ME, Garcia-Carmenate M, Silva-Valenzuela C, Baldoquin-Rodriguez W, Martínez-Pérez M, Rodríguez-González M, et al. Safety and efficacy of the two doses conjugated protein-based SOBERANA-02 COVID-19 vaccine and of a heterologous three-dose combination with SOBERANA-PLUS: double-blind, randomized, placebo-controlled phase 3 clinical trial. medRxiv 2021 [Preprint]. [DOI: 10.1101/2021.10.31.21265703] 10.1101/2021.10.31.21265703 PMC9803910 36618081 Voysey 2021a {published data only} Folegatti PM, Ewer KJ, Aley PK, Angus B, Becker S, Belij-Rammerstorfer S, et al. Safety and immunogenicity of the ChAdOx1 nCoV-19 vaccine against SARS-CoV-2: a preliminary report of a phase 1/2, single-blind, randomized controlled trial. Lancet 2020;396(10249):467-78. [PMID: ] PMC7445431 32702298 Voysey M, Clemens SA, Madhi SA, Weckx LY, Folegatti PM, Aley PK, et al. Safety and efficacy of the ChAdOx1 nCoV-19 vaccine (AZD1222) against SARS-CoV-2: an interim analysis of four randomized controlled trials in Brazil, South Africa, and the UK. Lancet 2021;397(10269):99-111. [PMID: ] PMC7723445 33306989 Walsh 2020 {published data only} Walsh EE, Frenck R, Falsey AR, Kitchin N, Absalon J, Gurtman A, et al. RNA-based COVID-19 vaccine BNT162b2 selected for a pivotal efficacy study. medRxiv 2020 [Preprint]. [DOI: 10.1101/2020.08.17.20176651] 10.1101/2020.08.17.20176651 Walsh EE, Frenck RW Jr, Falsey AR, Kitchin N, Absalon J, Gurtman A, et al. Safety and immunogenicity of two RNA-based Covid-19 vaccine candidates. New England Journal of Medicine 2020;383(25):2439-50. PMC7583697 33053279 Wu 2021a {published data only} Wu Z, Hu Y, Xu M, Chen Z, Yang W, Jiang Z, et al. Safety, tolerability, and immunogenicity of an inactivated SARS-CoV-2 vaccine (CoronaVac) in healthy adults aged 60 years and older: a randomized, double-blind, placebo-controlled, phase 1/2 clinical trial. Lancet Infectious Diseases 2021;21(6):803-12. PMC7906628 33548194 Xia 2020 {published data only} Xia S, Duan K, Zhang Y, Zhao D, Zhang H, Xie Z, et al. Effect of an inactivated vaccine against SARS-CoV-2 on safety and immunogenicity outcomes: interim analysis of 2 randomized clinical trials. JAMA 2020;324(10):951-60. PMC7426884 32789505 Xia S, Zhang Y, Wang Y, Wang H, Yang Y, Gao GF, et al. Safety and immunogenicity of an inactivated SARS-CoV-2 vaccine, BBIBP-CorV: a randomized, double-blind, placebo-controlled, phase 1/2 trial. Lancet Infectious Diseases 2020;21(1):39-51. PMC7561304 33069281 Xia 2021 {published data only} Xia S, Zhang Y, Wang Y, Wang H, Yang Y, Gao GF, et al. Safety and immunogenicity of an inactivated COVID-19 vaccine, BBIBP-CorV, in people younger than 18 years: a randomized, double-blind, controlled, phase 1/2 trial. Lancet Infectious Diseases 2021;22(2):196-208. PMC8443232 34536349 Zhang 2021 {published data only} Zhang Y, Zeng G, Pan H, Li C, Hu Y, Chu K, et al. Safety, tolerability, and immunogenicity of an inactivated SARS-CoV-2 vaccine in healthy adults aged 18–59 years: a randomized, double-blind, placebo-controlled, phase 1/2 clinical trial. Lancet Infectious Diseases 2021;21(2):181-92. PMC7832443 33217362 References to studies excluded from this review Baden 2021 {published data only} Baden LR, El Sahly HM, Essink B, Follmann D, Neuzil KM, August A, et al. Covid-19 in the phase 3 trial of mRNA-1273 during the Delta-variant surge. medRxiv 2021 [Preprint]. [DOI: 10.1101/2021.09.17.21263624] 10.1101/2021.09.17.21263624 PMC8609569 34731553 Barrett 2021 {published data only} Barrett JR, Belij-Rammerstorfer S, Dold C, Ewer KJ, Folegatti PM, Gilbride C, et al. Phase 1/2 trial of SARS-CoV-2 vaccine ChAdOx1 nCoV-19 with a booster dose induces multifunctional antibody responses. Nature Medicine 2021;27(2):279-88. 33335322 Ewer 2021 {published data only} Ewer KJ, Barrett JR, Belij-Rammerstorfer S, Sharpe H, Makinson R, Morter R, et al. T cell and antibody responses induced by a single dose of ChAdOx1 nCoV-19 (AZD1222) vaccine in a phase 1/2 clinical trial. Nature Medicine 2021;27(2):270-8. 33335323 Flaxman 2021 {published data only} Flaxman A, Marchevsky NG, Jenkin D, Aboagye J, Aley PK, Angus B, et al. Reactogenicity and immunogenicity after a late second dose or a third dose of ChAdOx1 nCoV-19 in the UK: a substudy of two randomized controlled trials (COV001 and COV002). Lancet 2021;398(10304):981-90. PMC8409975 34480858 Hsieh 2021 {published data only} Hsieh SM, Liu WD, Huang YS, Lin YJ, Hsieh EF, Lian WC, et al. Safety and immunogenicity of a recombinant stabilized prefusion SARS-CoV-2 spike protein vaccine (MVC-COV1901) adjuvanted with CpG 1018 and aluminum hydroxide in healthy adults: a phase 1, dose-escalation study. eClinicalMedicine 2021;38:100989. PMC8233066 34222848 Irfan 2021 {published data only} Irfan N, Chagla Z. In South Africa, a 2-dose Oxford/AZ vaccine did not prevent mild to moderate COVID-19 (cases mainly B.1.351 variant). Annals of Internal Medicine 2021;174(5):JC50. 33939483 Lazarus 2021 {published data only} Lazarus R, Baos S, Cappel-Porter H, Carson-Stevens A, Clout M, Culliford L, et al. The safety and immunogenicity of concomitant administration of COVID-19 vaccines (ChAdOx1 or BNT162b2) with seasonal influenza vaccines in adults: a phase IV, multicentre randomized controlled trial with blinding (ComFluCOV). SSRN 2021 [Preprint]. [DOI: 10.2139/ssrn.3931758] 10.2139/ssrn.3931758 PMC8585490 34774197 Patamatamkul 2021 {published data only} Patamatamkul S, Thammawat S, Buranrat B. Induction of robust neutralizing antibodies against the COVID-19 Delta variant with ChAdOx1 nCoV-19 or BNT162b2 as a booster following a primary vaccination series with CoronaVac. medRxiv 2021 [Preprint]. [DOI: 10.1101/2021.09.25.21264099] 10.1101/2021.09.25.21264099 Ward 2021a {published data only} Ward BJ, Séguin A, Couillard J, Trépanier S, Landry N. Phase III: randomized observer-blind trial to evaluate lot-to-lot consistency of a new plant-derived quadrivalent virus like particle influenza vaccine in adults 18-49 years of age. Vaccine 2021;39(10):1528-33. 33581920 Wu 2021b {published data only} Wu K, Choi A, Koch M, Ma LZ, Hill A, Nunna N, et al. Preliminary analysis of safety and immunogenicity of a SARS-CoV-2 variant vaccine booster. medRxiv 2021 [Preprint]. [DOI: 10.1101/2021.05.05.21256716] 10.1101/2021.05.05.21256716 PMC8604720 34526698 Zdanowski 2021 {published data only} Zdanowski W, Waśniewski T. Evaluation of SARS-CoV-2 spike protein antibody titers in cord blood after COVID-19 vaccination during pregnancy in Polish healthcare workers: preliminary results. Vaccines 2021;9(6):675. PMC8234119 34205434 Additional references Abbasi 2020 Abbasi J. 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