Abstract

COVID-19 is rapidly spreading causing extensive burdens across the world. Effective vaccines to prevent COVID-19 are urgently needed. Our objective was to assess the effectiveness and safety of COVID-19 vaccines through analyses of all currently available randomized clinical trials. We searched the databases CENTRAL, MEDLINE, Embase, and other sources from inception to June 17, 2021 for randomized clinical trials assessing vaccines for COVID-19. At least two independent reviewers screened studies, extracted data, and assessed risks of bias. We conducted meta-analyses, network meta-analyses, and Trial Sequential Analyses (TSA). Our primary outcomes included all-cause mortality, vaccine efficacy, and serious adverse events. We assessed the certainty of evidence with GRADE. We identified 46 trials; 35 trials randomizing 219 864 participants could be included in our analyses. Our meta-analyses showed that mRNA vaccines (efficacy, 95% [95% confidence interval (CI), 92% to 97%]; 71 514 participants; 3 trials; moderate certainty); inactivated vaccines (efficacy, 61% [95% CI, 52% to 68%]; 48 029 participants; 3 trials; moderate certainty); protein subunit vaccines (efficacy, 77% [95% CI, -5% to 95%]; 17 737 participants; 2 trials; low certainty); and viral vector vaccines (efficacy 68% [95% CI, 61% to 74%]; 71 401 participants; 5 trials; low certainty) prevented COVID-19. Viral vector vaccines decreased mortality (risk ratio, 0.25 [95% CI 0.09 to 0.67]; 67 563 participants; 3 trials, low certainty), but comparable data on inactivated, mRNA, and protein subunit vaccines were imprecise. None of the vaccines showed evidence of a difference on serious adverse events, but observational evidence suggested rare serious adverse events. All the vaccines increased the risk of non-serious adverse events. The evidence suggests that all the included vaccines are effective in preventing COVID-19. The mRNA vaccines seem most effective in preventing COVID-19, but viral vector vaccines seem most effective in reducing mortality. Further trials and longer follow-up are necessary to provide better insight into the safety profile of these vaccines.

Highlights

  • COVID-19 is caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-Cov-2) [1]

  • Our meta-analyses showed that mRNA vaccines (efficacy, 95% [95% confidence interval (CI), 92% to 97%]; 71 514 participants; 3 trials; moderate certainty); inactivated vaccines; protein subunit vaccines; and viral vector vaccines prevented COVID19

  • The evidence suggests that all the included vaccines are effective in preventing COVID-19

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Summary

Introduction

COVID-19 is caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-Cov-2) [1]. Since the observation of the first patients with COVID-19 in Wuhan in 2019, the disease quickly became a global pandemic [2]. As of September 6th, 2021 more than 221 million individuals developed COVID-19 and 4.6 million died globally [2]. There are only a few interventions hat seem able to benefit the clinical course of COVID-19 [3]. Preventive measures are of vital importance to control COVID-19. Approval of vaccines for COVID-19, and the growing number of viral variants, there is a need for systematic reviews critically appraising the topic. COVID-19 is rapidly spreading causing extensive burdens across the world. Effective vaccines to prevent COVID-19 are urgently needed

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