Cochrane Database of Systematic Reviews Review - Intervention Collapse all Expand all Résumé scientifique available in Contexte Différentes formes de vaccins ont été développées pour prévenir le virus SARS‐CoV‐2 et la COVID‐19 qui en découle. Plusieurs d'entre elles sont largement utilisées dans le monde. Objectifs Évaluer l'efficacité et la tolérance des vaccins contre la COVID‐19 (en tant que série complète de primovaccination ou dose de rappel) contre le SARS‐CoV‐2. Stratégie de recherche documentaire Nous avons effectué des recherches dans le registre Cochrane des études sur la COVID‐19 et dans la plateforme COVID‐19 L·OVE (dernière date de recherche le 5 novembre 2021). Nous avons également effectué des recherches sur le Système d'enregistrement international des essais cliniques (ICTRP) de l’OMS, sur les sites Web des organismes de réglementation et sur Retraction Watch. Critères de sélection Nous avons inclus des essais contrôlés randomisés (ECR) comparant les vaccins contre la COVID‐19 à un placebo, à l'absence de vaccin, à d'autres vaccins actifs ou à d'autres schémas vaccinaux. Recueil et analyse des données Nous avons utilisé les méthodes standard de Cochrane. Nous avons utilisé le système GRADE pour évaluer le niveau de confiance des données probantes pour tous les critères de jugement, à l'exception de l'immunogénicité. Nous avons synthétisé les données pour chaque vaccin séparément et présenté des estimations globales de l'effet avec des intervalles de confiance (IC) à 95 %. Résultats principaux Nous avons inclus et analysé 41 ECR évaluant 12 vaccins différents, y compris les schémas vaccinaux homologues et hétérologues et l'effet des doses de rappel. Trente‐deux ECR étaient multicentriques et cinq étaient multinationaux. La taille des échantillons des ECR était de 60 à 44 325 participants. Les participants étaient âgés: 18 ans ou plus dans 36 ECR ; 12 ans ou plus dans un ECR ; 12 à 17 ans dans deux ECR ; et 3 à 17 ans dans deux ECR. Vingt‐neuf ECR ont fourni des résultats pour des personnes âgées de plus de 60 ans, et trois ECR ont inclus des patients immunodéprimés. Aucun essai n'a inclus des femmes enceintes. Seize ECR avaient un suivi de deux mois ou moins, 20 ECR avaient un suivi de deux à six mois et cinq ECR avaient un suivi de plus de six à douze mois ou moins. Dix‐huit rapports étaient basés sur des analyses intérimaires planifiées à l'avance. Le risque global de biais était faible pour tous les critères de jugement dans huit ECR, tandis que 33 présentaient des problèmes pour au moins un critère de jugement. Nous avons identifié 343 ECR enregistrés dont les résultats ne sont pas encore disponibles. Ce résumé rapporte les résultats pour les critères de jugement critiques de la COVID‐19 symptomatique et confirmée, la forme sévère et critique de la COVID‐19, et des événements indésirables graves uniquement pour les 10 vaccins approuvés par l'OMS. Pour les autres critères de jugement et les vaccins, voir le texte principal. Les données probantes relatives à la mortalité étaient généralement éparses et d'un niveau de confiance faible ou très faible pour tous les vaccins approuvés par l'OMS, à l'exception du vaccin AD26.COV2.S (Janssen), qui réduit probablement le risque de mortalité toutes causes confondues (risque relatif (RR) 0,25, IC à 95 % 0,09 à 0,67 ; 1 ECR, 43 783 participants ; données probantes d’un niveau de confiance élevé). COVID‐19 symptomatique et confirmée Des données probantes d’un niveau de confiance élevé ont révélé que le BNT162b2 (BioNtech/Fosun Pharma/Pfizer), le mRNA‐1273 (ModernaTx), le ChAdOx1 (Oxford/AstraZeneca), l’Ad26.COV2.S, le BBIBP‐CorV (Sinopharm‐Beijing) et le BBV152 (Bharat Biotect) réduisent l'incidence de la COVID‐19 symptomatique par rapport au placebo (efficacité vaccinale (EV) : BNT162b2: 97,84 %, IC à 95 % 44,25 % à 99,92 % ; 2 ECR, 44 077 participants ; mRNA‐1273 : 93,20 %, IC à 95 % 91,06 % à 94,83 % ; 2 ECR, 31 632 participants ; ChAdOx1 : 70,23 %, IC à 95 % 62,10 % à 76,62 % ; 2 ECR, 43 390 participants ; Ad26.COV2.S : 66,90 %, IC à 95 % 59,10 % à 73,40 % ; 1 ECR, 39 058 participants ; BBIBP‐CorV : 78,10%, IC à 95 % 64,80 % à 86,30 % ; 1 ECR, 25 463 participants ; BBV152: 77,80 %, IC à 95 % 65,20 % à 86,40 % ; 1 ECR, 16 973 participants). Des données probantes d’un niveau de confiance modéré indiquent que le NVX‐CoV2373 (Novavax) réduit probablement l'incidence de la COVID‐19 symptomatique par rapport au placebo (EV 82,91 %, IC à 95 % 50,49 % à 94,10 % ; 3 ECR, 42 175 participants). Il existe des données probantes d’un niveau de confiance faible pour CoronaVac (Sinovac) pour ce critère de jugement (EV 69,81 %, IC à 95 % 12,27 % à 89,61 % ; 2 ECR, 19 852 participants). Forme sévère ou critique de la COVID‐19 Des données probantes d’un niveau de confiance élevé ont révélé que le BNT162b2, le mRNA‐1273, l’Ad26.COV2.S et le BBV152 entraînent une réduction importante de l'incidence de la forme sévère ou critique de la COVID‐19 par rapport au placebo (EV : BNT162b2: 95,70 %, IC à 95 % 73,90 % à 99,90 % ; 1 ECR, 46 077 participants ; mRNA‐1273 : 98,20 %, IC à 95 % 92,80 % à 99,60 % ; 1 ECR, 28 451 participants ; AD26.COV2.S : 76,30 %, IC à 95 % 57,90 % à 87,50 % ; 1 ECR, 39 058 participants ; BBV152: 93,40 %, IC à 95 % 57,10 % à 99,80 % ; 1 ECR, 16 976 participants). Des données probantes d’un niveau de confiance modéré ont montré que le NVX‐CoV2373 réduit probablement l'incidence de la forme sévère ou critique de la COVID‐19 (EV 100,00 %, IC à 95 % 86,99 % à 100,00 % ; 1 ECR, 25 452 participants). Deux essais ont rapporté une efficacité élevée de CoronaVac pour la forme sévère ou critique de la COVID‐19 avec des IC larges, mais ces résultats n'ont pas pu être regroupés. Événements indésirables graves (EIG) Le mRNA‐1273, le ChAdOx1 (Oxford‐AstraZeneca)/SII‐ChAdOx1 (Serum Institute of India), l’Ad26.COV2.S et le BBV152 entraînent probablement peu ou pas de différence dans les EIG par rapport au placebo (RR : mRNA‐1273 : 0,92, IC à 95 % 0,78 à 1,08 ; 2 ECR, 34 072 participants ; ChAdOx1/SII‐ChAdOx1 : 0,88, IC à 95 % 0,72 à 1,07 ; 7 ECR, 58 182 participants ; Ad26.COV2.S : 0,92, IC à 95 % 0,69 à 1,22 ; 1 ECR, 43 783 participants) ; BBV152: 0,65, IC à 95 % 0,43 à 0,97 ; 1 ECR, 25 928 participants). Dans chacun de ces résultats, la différence absolue probable des effets était inférieure à 5/1000 participants. Les données probantes des EIG sont incertaines pour le BNT162b2, le CoronaVac, le BBIBP‐CorV et le NVX‐CoV2373 par rapport au placebo (RR : BNT162b2: 1,30, IC à 95 % 0,55 à 3,07 ; 2 ECR, 46 107 participants ; CoronaVac : 0,97, IC à 95 % 0,62 à 1,51 ; 4 ECR, 23 139 participants ; BBIBP‐CorV : 0,76, IC à 95 % 0,54 à 1,06 ; 1 ECR, 26 924 participants ; NVX‐CoV2373: 0,92, IC à 95 % 0,74 à 1,14 ; 4 ECR, 38 802 participants). Pour l'évaluation des schémas hétérologues, des doses de rappel et de l'efficacité contre les variants préoccupants, voir le texte principal de la revue. Conclusions des auteurs Par rapport au placebo, la plupart des vaccins réduisent, ou réduisent probablement, la proportion de participants présentant une COVID‐19 symptomatique et confirmée, et pour certains, il existe des données probantes d’un niveau de confiance élevé indiquant qu'ils réduisent la forme sévère ou critique de la maladie. Il y a probablement peu ou pas de différence entre la plupart des vaccins et le placebo en ce qui concerne les événements indésirables graves. Plus de 300 ECR enregistrés évaluent l'efficacité des vaccins contre la COVID‐19, et cette revue est régulièrement mise à jour sur la plateforme COVID‐NMA(covid-nma.com). Implications pour la pratique En raison des critères d’exclusions des essais, ces résultats ne peuvent être généralisés aux femmes enceintes, aux personnes ayant des antécédents d'infection par le SARS‐CoV‐2 ou aux personnes immunodéprimées. La plupart des essais avaient un suivi court et ont été menés avant l'émergence des variants préoccupants. Implications pour la recherche Les recherches futures devraient évaluer l'effet à long terme des vaccins, comparer différents vaccins et schémas vaccinaux, évaluer l'efficacité et la tolérance des vaccins dans des populations spécifiques, et inclure des critères de jugement tels que la prévention de la COVID‐19 de longue durée. Il est également essentiel d'évaluer en permanence l'efficacité des vaccins et leur efficacité contre les nouveaux variants préoccupants. PICOs Population Intervention Comparison Outcome The PICO model is widely used and taught in evidence-based health care as a strategy for formulating questions and search strategies and for characterizing clinical studies or meta-analyses. PICO stands for four different potential components of a clinical question: Patient, Population or Problem; Intervention; Comparison; Outcome. See more on using PICO in the Cochrane Handbook. Résumé simplifié available in Quels sont les bénéfices et les risques des vaccins dans la prévention de la COVID‐19 ? Principaux messages ‐ La plupart des vaccins réduisent, ou réduisent probablement, le nombre de personnes qui contractent la COVID‐19 et la forme sévère de la COVID‐19. ‐ De nombreux vaccins sont susceptibles d'augmenter le nombre de personnes présentant des manifestations telles que fièvre ou maux de tête par rapport à un placebo (vaccin factice ne contenant aucun médicament mais ayant l'apparence du vaccin testé). Ceci est attendu car ces événements sont principalement dus à la réponse de l'organisme au vaccin ; ils sont généralement légers et de courte durée. ‐ De nombreux vaccins présentent peu ou pas de différence dans l'incidence des événements indésirables graves par rapport au placebo. ‐ Les données probantes sont insuffisantes pour déterminer s'il y avait une différence entre le vaccin et le placebo en termes de décès, car le nombre de décès était faible dans les essais. ‐ La plupart des essais ont évalué l'efficacité du vaccin sur une courte période, et n'ont pas évalué l'efficacité contre les variants préoccupants de la COVID‐19. Qu'est‐ce que le SARS‐CoV‐2 et la COVID‐19 ? Le SARS‐CoV‐2 (coronavirus 2 du syndrome respiratoire aigu sévère) est le virus à l'origine de la maladie à coronavirus 2 (COVID‐19). Les personnes infectées par le SARS‐CoV‐2 ne développent pas toutes les symptômes de la COVID‐19. Les symptômes peuvent être légers (fièvre et maux de tête, par exemple) ou menacer le pronostic vital (difficultés respiratoires, par exemple), voire entraîner la mort. Comment les vaccins préviennent‐ils la COVID‐19 ? Bien que les vaccins fonctionnent de manière légèrement différente, ils préparent tous le système immunitaire de l'organisme à empêcher les personnes d'être infectées par le SARS‐CoV‐2 ou, si elles le sont, à prévenir une forme sévère de la maladie. Que voulions‐nous découvrir ? Nous avons voulu savoir dans quelle mesure chaque vaccin est efficace pour réduire l'infection par le SARS‐CoV‐2, la COVID‐19 avec symptômes, la forme sévère de la COVID‐19 et le nombre total de décès (y compris tous les décès, pas seulement ceux liés à la COVID‐19). Nous voulions connaître les événements indésirables graves pouvant nécessiter une hospitalisation, mettre la vie en danger, ou les deux ; les événements de réactogénicité systémique (réactions immédiates à court terme aux vaccins principalement dues à des réponses immunologiques ; par exemple, fièvre, maux de tête, douleurs corporelles, fatigue) ; et tous les événements indésirables (qui comprennent les événements indésirables non graves). Qu'avons‐nous fait ? Nous avons recherché les études qui ont examiné tout vaccin contre la COVID‐19 comparé à un placebo, à l'absence de vaccin ou à un autre vaccin contre la COVID‐19. Nous n'avons retenu que les essais randomisés (un plan d'étude qui fournit les données probantes les plus solides car il évalue les interventions dans des conditions idéales parmi des participants assignés par hasard à l'un des deux groupes ou plus). Nous avons comparé et résumé les résultats des études, et évalué notre confiance dans les données probantes en fonction de facteurs tels que la manière dont l'étude a été menée. Qu'avons‐nous trouvé ? Nous avons trouvé 41 études mondiales impliquant 433 838 personnes et évaluant 12 vaccins différents. Trente‐cinq études n'ont inclus que des personnes en bonne santé qui n'avaient jamais eu la COVID‐19. Trente‐six études ne comprenaient que des adultes, deux que des adolescents, deux des enfants et des adolescents, et une comprenait des adolescents et des adultes. Trois ont étudié des personnes au système immunitaire affaibli, et aucune n'a étudié des femmes enceintes. Dans la plupart des cas, les résultats ont été évalués moins de six mois après la primovaccination. La plupart ont bénéficié d'un cofinancement de la part d'institutions universitaires et de sociétés pharmaceutiques. La plupart des études ont comparé un vaccin contre la COVID‐19 avec un placebo. Cinq d'entre eux ont évalué le mélange des vaccins pour la dose de rappel. Principaux résultats Nous présentons ci‐dessous les résultats pour trois critères de jugement principaux et pour dix vaccins approuvés par l'Organisation mondiale de la santé (OMS) (pour les autres critères de jugement et vaccins, voir le texte principal). Les données probantes concernant les décès sont insuffisantes entre les vaccins et le placebo (principalement car le nombre de décès était faible), à l'exception du vaccin Janssen, qui réduit probablement le risque de décès toutes causes confondues. Personnes présentant des symptômes Les vaccins Pfizer, Moderna, AstraZeneca, Sinopharm‐Beijing et Bharat entraînent une forte réduction du nombre de personnes présentant des symptômes de la COVID‐19. Le vaccin de Janssen réduit le nombre de personnes présentant des symptômes de la COVID‐19. Le vaccin Novavax a probablement permis de réduire considérablement le nombre de personnes présentant des symptômes de la COVID‐19. Les données probantes sont insuffisantes pour déterminer si le vaccin CoronaVac affecte le nombre de personnes présentant des symptômes de la COVID‐19 car les résultats diffèrent entre les deux études (l'une ne concernait que les travailleurs de la santé avec un risque d'exposition plus élevé). Forme sévère de la maladie Les vaccins Pfizer, Moderna, Janssen et Bharat permettent de réduire considérablement le nombre de personnes atteintes d'une forme sévère de la maladie. Les données probantes concernant le vaccin CoronaVac sur la forme sévère de la maladie sont insuffisantes car les résultats diffèrent entre les deux études (l'une ne concernait que les travailleurs de la santé, avec un risque d'exposition plus élevé). Événements indésirables graves Pour les vaccins Pfizer, CoronaVac, Sinopharm‐Beijing et Novavax, les données probantes sont insuffisantes pour déterminer s'il y avait une différence entre le vaccin et le placebo, principalement car le nombre d'événements indésirables graves était faible. Les vaccins Moderna, AstraZeneca, Janssen et Bharat n'entraînent probablement pas ou peu de différence dans le nombre d'événements indésirables graves. Quelles sont les limites des données probantes ? La plupart des études ont évalué le vaccin pendant une courte période après l'injection, et on ne sait pas si et comment la protection vaccinale s'estompe avec le temps. En raison des critères d'exclusion des essais des vaccins contre la COVID‐19, les résultats ne peuvent être généralisés aux femmes enceintes, aux personnes ayant des antécédents d'infection par le SARS‐CoV‐2 ou aux personnes dont le système immunitaire est affaibli. Des recherches supplémentaires sont nécessaires pour comparer les vaccins et les schémas vaccinaux, ainsi que l'efficacité et la sécurité dans des populations et des critères de jugement spécifiques (par exemple, la prévention de la COVID‐19 de longue durée). En outre, la plupart des études ont été menées avant l'émergence des variants préoccupants. Ces données probantes sont‐elles à jour ? Les données probantes sont à jour jusqu'en novembre 2021. Il s'agit d'une revue systématique dynamique. Nos résultats sont disponibles et mis à jour toutes les deux semaines sur la plateforme COVID‐NMA à l'adresse covid‐nma.com (disponibles en anglais). Authors' conclusions Implications for practice Several COVID‐19 vaccines are highly effective or probably highly effective in preventing SARS‐CoV‐2 infection, symptomatic COVID‐19 and severe or critical COVID‐19. There is moderate‐ to high‐certainty evidence that most vaccine candidates increased the risk of systemic reactogenicity events (e.g. fever). Evidence related to any adverse event was mainly uncertain. There is moderate‐ to high‐certainty evidence that there is probably no difference between mRNA‐1273, CVnCoV, ChAdOx1, Ad26.COV2.S, Gam‐COVID‐Vac, WIBP‐CorV and BBIBP‐CorV and placebo in terms of serious adverse events. Evidence was uncertain and very uncertain for serious adverse events for other vaccines and for all‐cause mortality for most vaccines, mainly because of the low number of events. In addition, as most RCTs only followed up participants for 2 months after full vaccination, all reports are related to short‐term impacts of the vaccine. Results cannot easily be generalized to pregnant women and immunocompromized individuals; more evidence is needed to elucidate the degree of additional protection conferred by COVID‐19 vaccines in these populations. Finally, the advent of variants of concern has highlighted the need for further research on each of the vaccine’s capacity to limit infection, disease, and death in regard to specific variants of concern. Implications for research Three hundred and forty‐four RCTs are currently registered, of which 10 are completed. The findings from these trials will contribute to the body of evidence on efficacy and safety outcomes. The findings of this review will be updated as soon as new data are available on the COVID‐NMA platform. Since the efficacy of vaccines is well established at this point, the ethics of RCT designs using a placebo as the comparison group should be questioned, and active comparators should be considered. With the notable impact of variants of concern on vaccine efficacy, it is crucial that variant type is assessed in clinical trials and reported for future meta‐analyses to assess vaccine efficacy on considerably different variants. As a non‐negligible global population has been infected by SARS‐CoV‐2, robust evidence‐based vaccination schemes are also required. Finally, considering the rapidly changing situation (in terms of variants, policies, etc.) and the increasing and important heterogeneity in the population in terms of combinations of vaccines received, history of SARS‐CoV‐2 infection (and by which variant), type of booster vaccine received, and predominant variants at the time of data collection, RCTs might become increasingly difficult to conduct in such a rapidly‐changing context and large population‐based observational studies could provide relevant information. Summary of findings Open in table viewerSummary of findings 1. BNT162b2 – Pfizer/BioNTech + Fosun Pharma compared to placebo for vaccination against COVID‐19a Outcomes Anticipated absolute effects* (95% CI) Relative effect(95% CI) № of participants Certainty of the evidence(GRADE) Comments Risk with placebo Risk with BNT162b2 Confirmed SARS‐CoV‐2 infection Outcome not yet measured or reported Confirmed symptomatic COVID‐19b 3923 per 100,000 85 per 100,000(3 to 2187) VE 97.84 (44.25 to 99.92) 44,077(2 RCTs)c ⊕⊕⊕⊕Highd — Severe or critical COVID‐19e 100 per 100,000 4 per 100,000(0 to 26) VE 95.70(73.90 to 99.90) 46,077(1 RCT)f ⊕⊕⊕⊕High — All‐cause mortalityg 64 per 100,000 68 per 100,000(33 to 142) RR 1.07(0.52 to 2.22) 43,847(1 RCT)f ⊕⊕⊖⊖Lowh 2 additional studies (Frenck 2021 (adolescents aged 12–15 years); Walsh 2020 (adults aged 18–85 years)) reported this outcome in 2302 participants (1131 versus 1129 participants and 24 versus 18 participants in the BNT162b2 versus placebo groups, respectively). There were no events in either group and the trials did not contribute to the effect estimate. Systemic reactogenicity events Outcome not yet measured or reported Any adverse eventi Outcome not pooled due to considerable heterogeneity (I² = 90%) between included studies: Thomas 2021 (≥ 16 years): RR 2.17, 95% CI 2.09 to 2.26; n = 43,847; Frenck 2021 (12–15 years): RR 1.01, 95% CI 0.73 to 1.41; n = 2260; Walsh 2020 (≥ 18 years): RR 1.50, 95% CI 0.53 to 4.21; n = 42 46,149(3 RCTs)j ⊕⊕⊖⊖Lowk — Serious adverse eventsi 508 per 100,000 660 per 100,000(279 to 1558) RR 1.30(0.55 to 3.07) 46,107(2 RCTs)c ⊕⊕⊖⊖Lowl,m 1 additional trial (Walsh 2020 (adults aged 18–85 years)) reported this outcome in 42 participants (24 BNT162b2 versus 18 placebo). There were no events in either group and the trial did not contribute to the effect estimate. Local reactogenicity events Outcome not yet measured or reported *The risk in the intervention group (and its 95% CI) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI). COVID‐19: coronavirus disease 2019;CI: confidence interval; RCT: randomized controlled trial; RR: risk ratio; SARS‐CoV‐2: severe acute respiratory syndrome coronavirus 2; VE: vaccine efficacy. GRADE Working Group grades of evidenceHigh certainty: we are very confident that the true effect lies close to that of the estimate of the effect.Moderate certainty: we are moderately confident in the effect estimate; the true effect is likely to be close to the estimate of the effect, but there is a possibility that it is substantially different.Low certainty: our confidence in the effect estimate is limited; the true effect may be substantially different from the estimate of the effect.Very low certainty: we have very little confidence in the effect estimate; the true effect is likely to be substantially different from the estimate of effect. aLast updated: 3 May 2022bFollow‐up: from 7 days following the second dose to 1.81 months and six months.cBioNTech/Fosun Pharma/Pfizer: Thomas 2021 (adolescents and adults aged from 16 years); Frenck 2021 (adolescents aged 12–15 years)dDespite some concerns with deviations from intervention, not downgraded for risk of bias.eFollow‐up: from seven days following the second dose to six months.fBioNTech/Fosun Pharma/Pfizer: Thomas 2021 (adolescents and adults aged from 16 years)gFollow‐up: six monthshImprecision: downgraded two levels due to small number of events observed and a wide CIs that encompasses a potential benefit and a potential harm with the intervention.iFollow‐up: 1.7 monthsjBioNTech/Fosun Pharma/Pfizer: Thomas 2021 (adolescents and adults aged from 16 years); Frenck 2021 (adolescents aged 12–15 years); Walsh 2020 (adults aged 18–85 years)kInconsistency: downgraded two levels (I² = 90%)lInconsistency: downgraded one level (I² = 76%)mImprecision: downgraded one level due to wide CIs consistent with the possibility of benefit and the possibility of harm. This outcome was not downgraded an additional level for imprecision because it was downgraded one level for inconsistency, which is related to and would have contributed to the severity of the imprecision. Open in table viewerSummary of findings 2. mRNA‐1273 – ModernaTX compared to placebo for vaccination against COVID‐19a Outcomes Anticipated absolute effects* (95% CI) Relative effect(95% CI) № of participants(studies) Certainty of the evidence(GRADE) Comments Risk with placebo Risk with mRNA‐1273 Confirmed SARS‐CoV‐2 infectionb 8957 per 100,000 2394 per 100,000(997 to 5749) VE 73.27(35.82 to 88.87) 31,632(2 RCTs)c ⨁⨁⨁◯Moderated,e Substantial heterogeneity (I² = 66%) between included studies: Ali 2021 (adolescents aged 12–17 years, median 2.3 months' follow‐up): VE 55.7% (95% CI 16.8 to 76.4), n = 3181; El Sahly 2021 (adults aged 18–95 years, 5.3 months' follow‐up): VE 82% (95% CI 79.5 to 84.2), n = 28,451 Confirmed symptomatic COVID‐19 b 4939 per 100,000 336 per 100,000(255 to 442) VE 93.20 (91.06 to 94.83) 31,632(2 RCTs)c ⨁⨁⨁⨁Highd — Severe or critical COVID‐19f 748 per 100,000 13 per 100,000(3 to 54) VE 98.20 (92.80 to 99.60) 28,451(1 RCT)g ⨁⨁⨁⨁Highd — All‐cause mortalityf 106 per 100,000 112 per 100,000(57 to 222) RR 1.06(0.54 to 2.10) 30,346(1 RCT)g ⨁⨁◯◯Lowh 1 additional trial: (Ali 2021 (adolescents aged 12–17 years)) reported on this outcome in 3726 participants (2486 mRNA‐1273 and 1240 placebo). There were no events in either group and the trial did not contribute to the pooled effect estimate Systemic reactogenicity eventsi 432 per 1000 553 per 1000(527 to 579) RR 1.28(1.22 to 1.34) 34,037(2 RCTs)c ⨁⨁⨁⨁Highj — Any adverse eventk Outcome not pooled due to considerable heterogeneity (I² = 100%) between included studies: Ali 2021 (all solicited adverse events, adolescents aged 12–17 years, median 2.8 months' follow‐up): RR 1.47 (95% CI 1.41 to 1.54), n = 3726; El Sahly 2021 (all solicited adverse events, adults aged 18–95 years, 5.3 months' follow‐up): RR 2.15 (95% CI 2.11 to 2.19), n = 29,269 — 32,995(2 RCTs)c ⨁⨁◯◯Lowl — Serious adverse eventsl 1792 per 100,000 1649 per 100,000(1398 to 1936) RR 0.92(0.78 to 1.08) 34,072(2 RCTs)c ⨁⨁⨁◯Moderatem — Local reactogenicity eventsi 211 per 1000 697 per 1000(427 to 1000) RR 3.30(2.02 to 5.40) 34,037(2 RCTs)c ⨁⨁⨁⨁Highn — *The risk in the intervention group (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI).COVID‐19: coronavirus disease 2019;CI: confidence interval; RCT: randomized controlled trial; RR: risk ratio; SARS‐CoV‐2: severe acute respiratory syndrome coronavirus 2; VE: vaccine efficacy. GRADE Working Group grades of evidenceHigh certainty: we are very confident that the true effect lies close to that of the estimate of the effect.Moderate certainty: we are moderately confident in the effect estimate: the true effect is likely to be close to the estimate of the effect, but there is a possibility that it is substantially different.Low certainty: our confidence in the effect estimate is limited: the true effect may be substantially different from the estimate of the effect.Very low certainty: we have very little confidence in the effect estimate: the true effect is likely to be substantially different from the estimate of effect. a. Last updated: 01 March 2023 b. Follow‐up: from 14 days after dose 2 to 2.3 months (median) and 5.3 months c. Moderna TX: Ali 2021 (adolescents aged 12–17 years); El Sahly 2021 (adults aged 18–95 years) d. Despite some concerns with deviations from intervention, not downgraded for risk of bias e. Inconsistency: downgraded one level: I² = 66.37% f. Follow‐up: 5.3 months g. Moderna TX: El Sahly 2021 (adults aged 18–95 years) h. Imprecision downgraded two levels due to small number of events observed and wide CIs that encompass a potential benefit and a potential harm with the intervention i. Follow‐up: seven days j. Despite inconsistency (I² = 61%) not downgraded for inconsistency, as the same direction of effect in both effect estimates k. Follow‐up: 2.8 months (median) and 5.3 months l. Inconsistency: downgraded two levels (I² = 100%) m. Imprecision: downgraded one level due to wide CIs that encompass a potential benefit and a potential harm with the intervention. n. Despite inconsistency (I² = 99%), not downgraded for inconsistency, as the same direction of effect in both effect estimates Open in table viewerSummary of findings 3. CVnCoV – CureVac AG compared to placebo for vaccination against COVID‐19a Outcomes Anticipated absolute effects* (95% CI) Relative effect(95% CI) № of participants(studies) Certainty of the evidence (GRADE) Comments Risk with placebo Risk with CVnCOV Confirmed SARS‐CoV‐2 infection Outcome not yet measured or reported Confirmed symptomatic COVID‐19b 1187 per 100,000 615 per 100,000(464 to 811) VE 48.20 (31.70 to 60.90) 25,062(1 RCT)c ⊕⊕⊕⊖Moderated,e — Severe or critical COVID‐19f 82 per 100,000 30 per 100,000(7 to 82) VE 63.80 (0.00 to 91.70) 25,062(1 RCT)c ⊕⊖⊖⊖Very lowd,e,g — All‐cause mortalityh 30 per 100,000 40 per 100,000(14 to 116) RR 1.33(0.46 to 3.83) 39,529(1 RCT)c ⊕⊖⊖⊖Very lowe,g — Systemic reactogenicity eventsi 635 per 1000 940 per 1000(908 to 971) RR 1.48(1.43 to 1.53) 3982(1 RCT)c ⊕⊕⊕⊕High — Any adverse eventj 679 per 1000 965 per 1000(937 to 999) RR 1.42(1.38 to 1.47) 3982(1 RCT)c ⊕⊕⊕⊖Moderatee — Serious adverse eventsk 334 per 100,000 414 per 100,000(301 to 572) RR 1.24(0.90 to 1.71) 39,529(1 RCT)c ⊕⊕⊖⊖Lowe,l — Local reactogenicity eventsi 241 per 1000 847 per 1000(782 to 920) RR 3.51(3.24 to 3.81) 3982(1 RCT)c ⊕⊕⊕⊕High — *The risk in the intervention group (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI). COVID‐19: coronavirus disease 2019CI: confidence interval; RCT: randomized controlled trial; RR: risk ratio; SARS‐CoV‐2: severe acute respiratory syndrome coronavirus 2; VE: vaccine efficacy. GRADE Working Group grades of evidenceHigh certainty: we are very confident that the true effect lies close to that of the estimate of the effect.Moderate certainty: we are moderately confident in the effect estimate; the true effect is likely to be close to the estimate of the effect, but there is a possibility that it is substantially different.Low certainty: our confidence in the effect estimate is limited; the true effect may be substantially different from the estimate of the effect.Very low certainty: we have very little confidence in the effect estimate; the true effect is likely to be substantially different from the estimate of effect. aLast updated: 10 May 2022bFollow‐up: from 14 days following the second dose to 6.23 monthscCureVac AG: Kremsner 2021 (adults aged 18–98 years)dDespite some concerns with deviations from intervention, not downgraded for risk of bias.eIndirectness: downgraded one level as data are from interim analyses of the trial and from the available information it is unclear whether these were preplanned.fFollow‐up: from seven days following the second dose to six monthsgImprecision: downgraded two levels due to small number of events observed and wide CIs that encompass a potential benefit and a potential harm with the intervention.hFollow‐up: 6.23 monthsiFollow‐up: seven daysjFollow‐up: one monthkFollow‐up: 1.7 monthslImprecision: downgraded one level due to wide CIs consistent with the possibility of benefit and the possibility of harm. Open in table viewerSummary of findings 4. ChAdOx1 – AstraZeneca + University of Oxford compared to placebo for vaccination against COVID‐19a Outcomes Anticipated absolute effects* (95% CI) Relative effect(95% CI) № of participants(studies) Certainty of the evidence Comments Risk with placebo Risk with ChAdOx1 Confirmed SARS‐CoV‐2 infectionb 3199 per 100,000 1300 per 100,000(1017 to 1663) VE 59.35 (48.00 to 68.22) 43,390(5 RCTs)c ⊕⊕⊕⊖Moderated,e Substantial heterogeneity (I² = 68%) between included studies: Falsey 2021 (VE 64.35%, 95% CI 56.10% to 71.00%; n = 26,212); Voysey 2021a (VE 54.10%, 95% CI 44.70% to 61.90%; n = 17,178) Confirmed symptomatic COVID‐19b 2207 per 100,000 657 per 100,000(516 to 836) VE 70.23 (62.10 to 76.62) 43,390(5 RCTs)c ⊕⊕⊕⊕Highd — Severe or critical COVID‐19 Outcome not yet measured or reported All‐cause mortalityf 52 per 100,000 25 per 100,000(10 to 59) RR 0.48(0.20 to 1.14) 56,727(5 RCTs)g ⊕⊕⊖⊖Lowh 2 additional trials (Asano 2022; Kulkarni 2021) reported this outcome in 1392 participants (192 ChAdOx1 versus 64 placebo and 900 SII‐ChAdOx1 versus 300 placebo, respectively). There were no events in either group in either trial and they did not contribute to the pooled effect estimate. Systemic reactogenicity eventsi 141 per 1000 553 per 1000(297 to 1000) RR 3.93(2.11 to 7.29) 256(1 RCT)j ⊕⊕⊕⊖Moderatek — Any adverse eventl Outcome not pooled due to considerable heterogeneity (I² = 90%) between included studies: Asano 2022 (RR 2.54, 95% CI 1.73 to 3.74; n = 256); Falsey 2021 (RR 1.37, 95% CI 1.33 to 1.42; n = 32,379); Kulkarni 2021 (RR 1.39, 95% CI 1.12 to 1.74; n = 1200); Voysey 2021a (RR 0.74, 95% CI 0.56 to 0.96; n = 23,745) — 57,580(7 RCTs)m ⊕⊕⊖⊖Lown — Serious adverse eventso 794 per 100,000 699 per 100,000(572 to 850) RR 0.88(0.72 to 1.07) 58,182(7 RCTs)p ⊕⊕⊕⊖Moderateq — Local reactogenicity eventsi 94 per 1000 604 per 1000(279 to 1000) RR 6.44(2.98 to 13.92) 256(1 RCT)j ⊕⊕⊕⊖Moderatek,r — *The risk in the intervention group (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI). COVID‐19: coronavirus disease 2019CI: confidence interval; RCT: randomized controlled trial; RR: risk ratio; SARS‐CoV‐2: severe acute respiratory syndrome coronavirus 2; VE: vaccine efficacy. GRADE Working Group grades of evidenceHigh certainty: we are very confident that the true effect lies close to that of the estimate of the effect.Moderate certainty: we are moderately confident in the effect estimate; the true effect is likely to be close to the estimate of the effect, but there is a possibility that it is substantially different.Low certainty: our confidence in the effect estimate is limited; the true effect may be substantially different from the estimate of the effect.Very low certainty: we have very little confidence in the effect estimate; the true effect is likely to be substantially different from the estimate of effect. aLast updated: 4 May 2022bFollow‐up: from 14 days after second dose up to 1.34 months (median) and 2 months (median)cFalsey 2021; Voysey 2021a (data from four pooled RCTs)dDespite some concerns with deviations from intervention, not downgraded for risk of bias.eInconsistency: downgraded one level (I² = 68%).fFollow‐up: 2 months, 4.2 months and 2 months (median)gFalsey 2021; Voysey 2021a (data from four pooled RCTs); Madhi 2021a (participants with HIV, trial already counted in Voysey 2021a)hImprecision: downgraded two levels due to small number of events observed and wide CIs that encompass a potential benefit and a potential harm with the intervention.iFollow‐up: seven daysjAsano 2022kImprecision: downgraded one level due to low number of participants/few events observed.lFollow‐up: 1 month, 1.16 months, 1.9 months, and 3.4 monthsmAsano 2022; Falsey 2021; Kulkarni 2021; Voysey 2021a (data from four pooled RCTs)nInconsistency: downgraded two levels (I² = 90%).oFollow‐up: 1 month, 1.9 months, 6 months, and 3.64 months (median)pAsano 2022; Falsey 2021; Kulkarni 2021; Voysey 2021a (data from four pooled RCTs). Madhi 2021a (participants with HIV, trial already counted in Voysey 2021a)qImprecision: downgraded one level due to wide CIs consistent with the possibility of benefit and the possibility of no effect.rDespite some concerns with selection of reported results, not downgraded for risk of bias. Open in table viewerSummary of findings 5. SII‐ChAdOx1 – Serum Institute of India/AstraZeneca + University of Oxford compared to ChAdOx1 – University of Oxford for vaccination against COVID‐19a Outcomes Anticipated absolute effects* (95% CI) Relative effect(95% CI) № of participants(studies) Certainty of the evidence(GRADE) Comments Risk with ChAdOx1 Risk with SII‐ChAdOx1 Confirmed SARS‐CoV‐2 infection Outcome not yet measured or reported Confirmed symptomatic COVID‐19 Outcome not yet measured or reported Severe or critical COVID‐19 Outcome not yet measured or reported All‐cause mortality — — — — — 1 study reported this outcome in 400 participants (Kulkarni 2021). There were no events in either group and no effect estimate could be calculated. Systemic reactogenicity eventsb 390 per 1000 285 per 1000(211 to 382) RR 0.73(0.54 to 0.98) 400(1 RCT)c ⊕⊕⊕⊖Moderated — Any adverse evente 200 per 1000 166 per 1000(104 to 266) RR 0.83(0.52 to 1.33) 400(1 RCT)c ⊕⊕⊖⊖Lowf — Serious adverse eventsg 2000 per 100,000 1000 per 100,000(160 to 5900) RR 0.50(0.08 to 2.95) 400(1 RCT)c ⊕⊕⊖⊖Lowf — Local reactogenicity eventsb 360 per 1000 274 per 1000(198 to 378) RR 0.76(0.55 to 1.05) 400(1 RCT)c ⊕⊕⊖⊖Lowh — *The risk in the intervention group (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI). COVID‐19: coronavirus disease 2019CI: confidence interval; RCT: randomized controlled trial; RR: risk ratio; SARS‐CoV‐2: severe acute respiratory syndrome coronavirus 2. GRADE Working Group grades of evidenceHigh certainty: we are very confident that the true effect lies close to that of the estimate of the effect.Moderate certainty: we are moderately confident in the effect estimate; the true effect is likely to be close to the estimate of the effect, but there is a possibility that it is substantially different.Low certainty: our confidence in the effect estimate is limited; the true effect may be substantially different from the estimate of the effect.Very low certainty: we have very little confidence in the effect estimate; the true effect is likely to be substantially different from the estimate of effect. aLast updated: 10 May 2022bFollow‐up: seven dayscKulkarni 2021dImprecision: downgraded one level due to low number of events/participants.eFollow‐up: 1.9 monthsfImprecision: downgraded two levels due to wide CIs consistent with the possibility of benefit and the possibility of harm and low number of events/participants.gFollow‐up: six monthshImprecision: downgraded two levels due to wide CIs consistent with the possibility of no effect and the possibility of benefit and low number of events/participants. Open in table viewerSummary of findings 6. AD26.COV2.S – Janssen Pharmaceutical Companies compared to placebo for vaccination against COVID‐19a Outcomes Anticipated absolute effects* (95% CI) Relative effect(95% CI) № of participants(studies) Certainty of the evidence(GRADE) Comments Risk with placebo Risk with AD26.COV2.S Confirmed SARS‐CoV‐2 infection Outcome not yet measured or reported Confirmed symptomatic COVID‐19b 1796 per 100,000 594 per 100,000(478 to 735) VE 66.90 (59.10 to 73.40) 39,058(1 RCT)c ⊕⊕⊕⊕Highd — Severe or critical COVID‐19b 409 per 100,000 97 per 100,000(51 to 172) VE 76.30 (57.90 to 87.50) 39,058(1 RCT)c ⊕⊕⊕⊕Highd — All‐cause mortalityb 91 per 100,000 23 per 100,000(8 to 61) RR 0.25(0.09 to 0.67) 43,783(1 RCT)c ⊕⊕⊕⊕High — Serious adverse eventsb 448 per 100,000 412 per 100,000(309 to 546) RR 0.92(0.69 to 1.22) 43,783(1 RCT)c ⊕⊕⊕⊖Moderatej — Systemic reactogenicity eventse 34,575 per 100,000 63,273 per 100,000(44,602 to 89,896) RR 1.83(1.29 to 2.60) 7222(2 RCTs)f ⊕⊕⊕⊕Highd,g — Any adverse eventh Outcome not pooled due to considerable heterogeneity (I² = 96%) between included studies: Sadoff 2021a (RR 1.09, 95% CI 0.96 to 1.24; n = 6736); Sadoff 2021b (RR 2.31, 95% CI 1.80 to 2.97; n = 486) — 7222(2 RCTs)f ⊕⊕⊖⊖Lowd,i — *The risk in the intervention group (and its 95% CI) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI). COVID‐19: coronavirus disease 2019CI: confidence interval; RCT: randomized controlled trial; RR: risk ratio; SARS‐CoV‐2: severe acute respiratory syndrome coronavirus 2; VE: vaccine efficacy. GRADE Working Group grades of evidenceHigh certainty: we are very confident that the true effect lies close to that of the estimate of the effect.Moderate certainty: we are moderately confident in the effect estimate; the true effect is likely to be close to the estimate of the effect, but there is a possibility that it is substantially different.Low certainty: our confidence in the effect estimate is limited; the true effect may be substantially different from the estimate of the effect.Very low certainty: we have very little confidence in the effect estimate; the true effect is likely to be substantially different from the estimate of effect. aLast updated: 4 May 2022bFollow‐up: 1.9 months (median)cSadoff 2021bdDespite some concerns with deviations from intervention, not downgraded for risk of bias.eFollow‐up: seven days and 14 daysfSadoff 2021a; Sadoff 2021bgDespite I² = 83%, not downgraded for inconsistency, as the same direction of effect in both effect estimates.hFollow‐up: 0.23 months and 0.92 monthsiInconsistency: downgraded two levels (I² = 96%).jImprecision: downgraded one level due to wide CIs consistent with the possibility of no effect and the possibility of benefit.kFollow‐up: seven dayslDespite I² = 84%, not downgraded for inconsistency, as the same direction of effect in both effect estimates. Open in table viewerSummary of findings 7. Gam‐COVID‐VAC – Sputnik V compared to placebo for vaccination against COVID‐19a Outcomes Anticipated absolute effects* (95% CI) Relative effect(95% CI) № of participants(studies) Certainty of the evidence(GRADE) Comments Risk with placebo Risk with Gam‐COVID‐VAC Confirmed SARS‐CoV‐2 infection Outcome not yet measured or reported Confirmed symptomatic COVID‐19b 1022 per 100,000 92 per 100,000(51 to 167) VE 91.10 (83.80 to 95.10) 18,695(1 RCT)c ⊕⊕⊕⊖Moderated,e — Severe or critical COVID‐19b 408 per 100,000 0 per 100,000(0 to 23) VE 100.00 (94.40 to 100.00) 19,866(1 RCT)c ⊕⊕⊕⊖Moderated,e — All‐cause mortalityf 18 per 100,000 18 per 100,000(2 to 176) RR 0.99(0.10 to 9.54) 21,862(1 RCT)c ⊕⊖⊖⊖Very lowd,e,g — Systemic reactogenicity events Outcome not yet measured or reported Any adverse event Outcome not yet measured or reported Serious adverse eventsf 423 per 100,000 275 per 100,000(165 to 453) RR 0.65(0.39 to 1.07) 21,862(1 RCT)c ⊕⊕⊖⊖Lowd,e,h — Local reactogenicity events Outcome not yet measured or reported *The risk in the intervention group (and its 95% CI) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI). COVID‐19: coronavirus disease 2019;CI: confidence interval; RCT: randomized controlled trial; RR: risk ratio; SARS‐CoV‐2: severe acute respiratory syndrome coronavirus 2; VE: vaccine efficacy. GRADE Working Group grades of evidenceHigh certainty: we are very confident that the true effect lies close to that of the estimate of the effect.Moderate certainty: we are moderately confident in the effect estimate; the true effect is likely to be close to the estimate of the effect, but there is a possibility that it is substantially different.Low certainty: our confidence in the effect estimate is limited; the true effect may be substantially different from the estimate of the effect.Very low certainty: we have very little confidence in the effect estimate; the true effect is likely to be substantially different from the estimate of effect. aLast updated: 27 May 2022bFollow‐up: from seven days after second dosecLogunov 2021dIndirectness: downgraded one level as data are from interim analyses of the trial and from the available information it is unclear whether these were preplanned.eConcern regarding the internal validity of the trial.fFollow‐up: 1.6 months (median)gImprecision: downgraded two levels due to wide CIs consistent with the possibility of benefit and the possibility of harm and few events.hImprecision: downgraded one level due to wide CIs consistent with the possibility of no effect and the possibility of benefit. Open in table viewerSummary of findings 8. CoronaVac – Sinovac compared to placebo for vaccination against COVID‐19a Outcomes Anticipated absolute effects* (95% CI) Relative effect № of participants(studies) Certainty of the evidence(GRADE) Comments Risk with placebo Risk with CoronaVac Confirmed SARS‐CoV‐2 infection Outcome not yet measured or reported Confirmed symptomatic COVID‐19b 2398 per 100,000 724 per 100,000(249 to 2104) VE 69.81 (12.27 to 89.61) 19,852(2 RCTs)c ⊕⊕⊖⊖Lowd,e,f Considerable heterogeneity (I² = 92%) between included studies: Tanriover 2021 (VE 83.50%, 95% CI 65.40% to 92.10%; n = 10,029); Palacios 2020 (VE 50.70%, 95% CI 35.90 to 62.00%; n = 9823) Severe or critical COVID‐19b 2 studies report on severe or critical disease due to COVID‐19: Tanriover 2021, with 0/6559 events in the CoronaVac group versus 1/3470 events in the placebo group and a VE of 100%, 95% CI (20.40% to 100.00%); and Palacios 2020, with 0/4953 events in the CoronaVac group and 6/4870 events in the placebo group and a VE of 100%, 95% CI (16.90% to 100.00%). (Note: estimates could not be pooled due to asymmetry in the CIs) — 19,852(2 RCTs)c ⊕⊕⊖⊖Lowd,g — All‐cause mortalityh 20 per 100,000 10 per 100,000(1 to 113) RR 0.50(0.05 to 5.52) 22,610(2 RCTs)c ⊕⊕⊖⊖Lowi — Systemic reactogenicity eventsj 409 per 1000 487 per 1000(409 to 581) RR 1.19(1.00 to 1.42) 23,966(6 RCTs)k ⊕⊕⊖⊖Lowl,m,n — Any adverse evento 531 per 1000 579 per 1000(568 to 590) RR 1.09(1.07 to 1.11) 23,367(6 RCTs)p ⊕⊕⊕⊕Highq — Serious adverse eventsr 372 per 100,000 361 per 100,000(231 to 562) RR 0.97(0.62 to 1.51) 23,139(4 RCTs)s ⊕⊕⊖⊖Lowi,q 2 additional trials (Bueno 2021; Zhang 2021) reported this outcome in 482 participants (270 versus 164 and 24 versus 24 respectively, receiving CoronaVac versus placebo). There were no events in either group and the trials did not contribute to the pooled effect estimate. Local reactogenicity eventsj 227 per 1000 400 per 1000(384 to 414) RR 1.76(1.69 to 1.82) 23,962(6 RCTs)k ⊕⊕⊕⊕Highl — *The risk in the intervention group (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI). COVID‐19: coronavirus disease 2019CI: confidence interval; RCT: randomized controlled trial; RR: risk ratio; SARS‐CoV‐2: severe acute respiratory syndrome coronavirus 2; VE: vaccine efficacy. GRADE Working Group grades of evidenceHigh certainty: we are very confident that the true effect lies close to that of the estimate of the effect.Moderate certainty: we are moderately confident in the effect estimate; the true effect is likely to be close to the estimate of the effect, but there is a possibility that it is substantially different.Low certainty: our confidence in the effect estimate is limited; the true effect may be substantially different from the estimate of the effect.Very low certainty: we have very little confidence in the effect estimate; the true effect is likely to be substantially different from the estimate of effect. aLast updated: 4 May 2022bFollow‐up: from 14 days after the second dose up to two months (median)cPalacios 2020; Tanriover 2021dDespite some concerns with deviations from intervention, not downgraded for risk of bias.eInconsistency: downgraded one level (I² = 92%).fImprecision: downgraded one level due to wide CIs consistent with the possibility of benefit and the possibility of harm.gImprecision: downgraded two levels due to low number of events and wide CIs.hFollow‐up: 1.4 and 2 months (median)iImprecision: downgraded two levels due to wide CIs consistent with the possibility of benefit and the possibility of harm and few events.jFollow‐up: 7–28 dayskBueno 2021; Fadlyana 2021; Palacios 2020; Tanriover 2021; Wu 2021a; Zhang 2021lDespite some concerns with adequate randomisation, deviation from intended intervention, missing data, and selection of reported results not downgraded for risk of bias.mInconsistency: downgraded one level (I² = 55%).nImprecision: downgraded one level due to wide CIs consistent with the possibility of no effect and the possibility of harm.oFollow‐up: one to three months (median)pBueno 2021; Han 2021; Palacios 2020; Tanriover 2021; Wu 2021a; Zhang 2021qDespite some concerns with adequate randomisation, not downgraded for risk of bias.rFollow‐up: 4.1 months, 2 months (median), 3 months (median)sHan 2021; Palacios 2020; Tanriover 2021; Wu 2021a Open in table viewerSummary of findings 9. WIBP‐CorV – Sinopharm‐Wuhan compared to placebo for vaccination against COVID‐19a Outcomes Anticipated absolute effects* (95% CI) Relative effect(95% CI) № of participants Certainty of the evidence(GRADE) Comments Risk with placebo Risk with WIBP‐CorV Confirmed SARS‐CoV‐2 infectionb 912 per 100,000 328 per 100,000(231 to 467) VE 64.00 (48.80 to 74.70) 25,449(1 RCT)c ⊕⊕⊕⊕Highd — Confirmed symptomatic COVID‐19b 746 per 100,000 203 per 100,000(131 to 313) VE 72.80 (58.10 to 82.40) 25,480(1 RCT)c ⊕⊕⊕⊕Highd — Severe or critical COVID‐19 Outcome not yet measured or reported All‐cause mortality — — — — — 1 trial reported on this outcome in 26,917 participants (13,464 WIBP‐CorV versus 13,453 placebo) (Al Kaabi 2021). There were no events in either group and no effect estimate could be calculated for this outcome. Systemic reactogenicity eventse 278 per 1000 275 per 1000(264 to 286) RR 0.99(0.95 to 1.03) 27,029(2 RCTs)f ⊕⊕⊕⊕Highg — Any adverse eventh 504 per 1000 484 per 1000(469 to 494) RR 0.96(0.93 to 0.98) 27,029(2 RCTs)f ⊕⊕⊕⊕High — Serious adverse eventsi 579 per 100,000 480 per 100,000(347 to 665) RR 0.83(0.60 to 1.15) 27,029(2 RCTs)f ⊕⊕⊖⊖Lowg,j — Local reactogenicity eventsk 290 per 1000 255 per 1000(247 to 267) RR 0.88(0.85 to 0.92) 27,029(2 RCTs)f ⊕⊕⊕⊕Highg — *The risk in the intervention group (and its 95% CI) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI). COVID‐19: coronavirus disease 2019CI: confidence interval; RCT: randomized controlled trial; RR: risk ratio; SARS‐CoV‐2: severe acute respiratory syndrome coronavirus 2; VE: vaccine efficacy. GRADE Working Group grades of evidenceHigh certainty: we are very confident that the true effect lies close to that of the estimate of the effect.Moderate certainty: we are moderately confident in the effect estimate; the true effect is likely to be close to the estimate of the effect, but there is a possibility that it is substantially different.Low certainty: our confidence in the effect estimate is limited; the true effect may be substantially different from the estimate of the effect.Very low certainty: we have very little confidence in the effect estimate; the true effect is likely to be substantially different from the estimate of effect. aLast updated: 4 May 2022bFollow‐up: from 2 weeks after the second dose up to 2.6 months (median)cAl Kaabi 2021dDespite some concerns with deviations from intervention, not downgraded for risk of bias.eFollow‐up: seven days and 28 daysfAl Kaabi 2021; Guo 2021gDespite some concerns with adequate randomisation, not downgraded for risk of bias.hFollow‐up: one monthiFollow‐up: 1.6 and 2.6 months (median)jImprecision: downgraded two levels due to wide CIs consistent with the possibility of no effect and the possibility of benefit and few events.kFollow‐up: seven days Open in table viewerSummary of findings 10. BBIBP‐CorV – Sinopharm‐Beijing compared to placebo for vaccination against COVID‐19a Outcomes Anticipated absolute effects* (95% CI) Relative effect(95% CI) № of participants(studies) Certainty of the evidence(GRADE) Comments Risk with placebo Risk with BBIBP‐CorV Confirmed SARS‐CoV‐2 infectionb 912 per 100,000 242 per 100,000(162 to 359) VE 73.50 (60.60 to 82.20) 25,435(1 RCT)c ⊕⊕⊕⊕Highd — Confirmed symptomatic COVID‐19b 746 per 100,000 163 per 100,000(102 to 263) VE 78.10 (64.80 to 86.30) 25,463(1 RCT)c ⊕⊕⊕⊕Highd — Severe or critical COVID‐19 Outcome not yet measured or reported All‐cause mortality — — — — — 1 study reported this outcome in 26,924 participants (13,471 BBIBP‐CorV versus 13,453 placebo) (Al Kaabi 2021). There were no events in either group and no effect estimate could be calculated for this outcome. Systemic reactogenicity eventse 274 per 1000 288 per 1000(236 to 351) RR 1.05(0.86 to 1.28) 27,540(3 RCTs)f ⊕⊕⊕⊖Moderateg — Any adverse eventh 3 studies (n = 27,540) reported any adverse event with 1 month or 2.9 months' follow‐up. 2 of the studies reported an effect estimate in favour of BBIBP‐CorV: 1 with RR 0.91, 95% CI 0.89 to 0.94; n = 26,924; and 1 with CIs crossing the line of no effect (RR 0.83, 95% CI 0.36 to 1.95; n = 112). 1 study reported an effect estimate in favour of placebo with CIs not crossing the line of null effect (RR 2.05, 95% CI 1.47 to 2.87; n = 504) — 26,924(3 RCTs)f ⊕⊕⊖⊖Lowi,j — Serious adverse eventsk 580 per 100,000 441 per 100,000(313 to 615) RR 0.76(0.54 to 1.06) 26,924(1 RCT)c ⊕⊕⊖⊖Lowl 1 additional study reported this outcome in 112 participants (84 BBIBP‐CorV versus 28 placebo) (Xia 2020). There were no events in either group and the trial did not contribute to the effect estimate. Local reactogenicity eventse 3 studies (n = 27,540) reported local adverse events with 7 days' follow‐up. 1 study reported an effect estimate in favour of BBIBP‐CorV: RR 0.71, 95% CI 0.68 to 0.74; n = 26,924. 2 studies reported an effect estimate in favour of placebo with CIs not crossing the line of null effect (RR 10.00, 95% CI 2.36 to 42.34; n = 504 and RR 3.33, 95% CI 0.45 to 24.89; n = 112). — 26,924(3 RCTs)f ⊕⊕⊖⊖Lowi,j — *The risk in the intervention group (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI). COVID‐19: coronavirus disease 2019CI: confidence interval; RCT: randomized controlled trial; RR: risk ratio; SARS‐CoV‐2: severe acute respiratory syndrome coronavirus 2; VE: vaccine efficacy. GRADE Working Group grades of evidenceHigh certainty: we are very confident that the true effect lies close to that of the estimate of the effect.Moderate certainty: we are moderately confident in the effect estimate; the true effect is likely to be close to the estimate of the effect, but there is a possibility that it is substantially different.Low certainty: our confidence in the effect estimate is limited; the true effect may be substantially different from the estimate of the effect.Very low certainty: we ha