Vaccines to Prevent COVID-19: A Living Systematic Review With Trial Sequential Analysis and Network Meta-Analysis of Randomised Controlled Trials

Abstract

Background: COVID-19 is a rapidly spreading disease that is causing extensive burdens across the world. Effective vaccines to prevent COVID-19 are urgently needed. Several vaccines have been accepted by regulatory authorities, but their individual and relative efficacy and adverse effects remain unclear.Methods: We conducted a systematic review of randomised clinical trials with network meta-analysis and Trial Sequential Analysis (TSA). Searches were made in CENTRAL, MEDLINE, Embase, and other sources from inception to May 12, 2021 for randomised clinical trials, assessing vaccines for COVID-19 . At least two independent reviewers screened studies, extracted data, and assessed the risk of bias. Our primary outcomes included all-cause mortality, vaccine efficacy, and serious adverse events.Findings We identified 22 trials; 19 trials randomising 144 434 participants were included in our analyses. mRNA vaccines (efficacy 95%, 95% confidence interval (CI) 92% to 97%; 69 285 participants; 2 trials; GRADE: moderate certainty) and viral vector vaccines (efficacy 68%, 95% CI 61% to 74%; 71 401 participants; 5 trials; GRADE: low certainty) prevented COVID-19. Viral vector vaccines decreased mortality (risk ratio (RR) 0·25, 95% CI 0·09 to 0·67; 67 563 participants; 3 trials, GRADE: low certainty), but data on mRNA vaccines are still imprecise. None of the vaccines showed evidence of a difference on serious adverse events, but observational evidence indicated rare serious adverse events. mRNA and viral vector vaccines increased the risk of non-serious adverse events. Interpretation The evidence suggests that mRNA vaccines and viral vector vaccines are effective in preventing COVID-19. mRNA vaccines seem most effective in preventing COVID-19, but viral vector vaccines seem most effective in reducing mortality. mRNA vaccines and viral vector vaccines increase the risks of rare serious adverse events according to observational evidence. Further trials and longer follow-up are necessary to provide better insight into the safety profile of these vaccines. Registration Information: PROSPERO CRD42020196492. Funding Information: The Copenhagen Trial Unit funded the wages for the authors affiliated with the Copenhagen Trial Unit. None of the authors received any specific funding related to the review. Declaration of Interests: The authors declare that they have no known competing interests.