mRNA vaccines appear to be most effective for symptomatic COVID-19 prevention while viral vector vaccines appear to be most efficacious for mortality reduction.

This systematic review with trial sequential analysis and network meta-analysis of randomized clinical trials was performed to determine safety and efficacy of SARS-CoV-2 vaccines via assessment of all the currently available trials.

Databases like Embase, CENTRAL, MEDLINE, and other sources were comprehensively explored for randomized clinical trials investigating vaccines for coronavirus disease. Screening of studies, data extraction and assessment of risks of bias was done. All-cause mortality, vaccine efficacy, and severe side effects were the major endpoints ascertained. Utilizing Grading of Recommendation, Assessment, Development and Evaluation (GRADE), the certainty of the evidence was examined.

A total of 35 trials randomizing 219 864 people provided data for the predefined meta-analyses. mRNA vaccines (95% effectiveness; 71514 volunteers; 3 trials; moderate certainty); inactivated vaccines (61% effectiveness; 48029 volunteers; 3 trials; moderate certainty); protein subunit vaccines (77% effectiveness; 17 737 volunteers; 2 trials; low certainty); and viral vector vaccines (68% effectiveness; 71401 volunteers; 5 trials; low certainty) prevented coronavirus disease.

As found, viral vector vaccines reduced mortality (risk ratio 0.25; 67 563 volunteers; 3 trials, low certainty). However, comparable data on protein subunit, inactivated, and mRNA vaccines were not precise. In the study, none of the vaccines illustrated evidence of a difference in severe side effects. However, observational evidence revealed rare severe side effects. All the vaccines were reported to raise the risk of non-severe side effects.

Inactivated vaccines, viral vector vaccines, mRNA vaccines, and protein-subunit vaccines are effective to prevent SARS-CoV-2 infection. For a better insight into the safety profile of vaccines, additional robust trials and longer follow-up are warranted.