Randomised Clinical Trials of COVID-19 Vaccines: Do Adenovirus-Vector Vaccines Have Beneficial Non-Specific Effects?
To examine the possible non-specific effects (NSEs) of the novel COVID-19 vaccines, we reviewed the randomised control trials (RCTs) of mRNA and adenovirus-vector COVID-19 vaccines reporting overall mortality, including COVID-19 deaths, accident deaths, cardiovascular deaths and other non-COVID-19 deaths. For overall mortality, with 74,193 participants and 61 deaths (mRNA:31; placebo:30), the relative risk (RR) for the two mRNA vaccines compared with placebo was 1.03 (95% CI=0.63-1.71). In the adenovirus-vector vaccines there were 122,164 participants and 46 deaths (vaccine:16; controls:30). The RR for adenovirus-vector vaccines versus placebo/control vaccine was 0.37 (0.19-0.70). The adenovirus-vector vaccines were associated with protection against COVID-19 deaths (RR=0.11 (0.02-0.87)) and non-accident, non-COVID-19 deaths (RR=0.38 (0.17-0.88)). The two types of vaccines differed significantly with respect to impact on overall mortality (p=0.030) as well as non-accident, non-COVID-19 deaths (p=0.046). The placebo controlled RCTs of COVID-19 vaccines were halted rapidly due to clear effects on COVID-19 infections. However, the data presented here argue for performing RCTs of mRNA and adeno-vectored vaccines head-to-head comparing long-term effects on overall mortality.