Randomized clinical trials of COVID-19 vaccines: do adenovirus-vector vaccines have beneficial non-specific effects?

ABSTRACT

We examined the possible non-specific effects of novel mRNA- and adenovirus-vector COVID-19 vaccines by reviewing the randomized control trials (RCTs) of mRNA and adenovirus-vector COVID-19 vaccines. We calculated mortality risk ratios (RR) for mRNA COVID-19 vaccines vs. placebo recipients and compared them with the RR for adenovirus-vector COVID-19 vaccine recipients vs. controls. The RR for overall mortality of mRNA vaccines vs. placebo was 1.03 (95% CI 0.63-1.71). In the adenovirus-vector vaccine RCTs, the RR for overall mortality was 0.37 (0.19-0.70). The two vaccine types differed significantly with respect to impact on overall mortality (p=0.015). The RCTs of COVID-19 vaccines were unblinded rapidly and controls were vaccinated. The results may therefore not be representative of the long-term effects. However, the data argues for performing RCTs of mRNA and adenovirus-vector vaccines head-to-head comparing long-term effects on overall mortality. Graphical With a mortality risk ratio (RR) of 1.03 (95% CI 0.63-1.71), there was no difference in overall mortality for recipients of mRNA vaccines and controls in the randomized trials. In the adenovirus-vector vaccine trials the RR for vaccinated and controls was 0.37 (0.19-0.70).