Factors Influencing the Efficacy of COVID-19 Vaccines: A Quantitative Synthesis of Phase III Trials

To date, there is still a paucity of data from Phase III trials concerning the efficacy of vaccines against COVID-19. Furthermore, no studies investigated the variables that may modulate the efficacy of vaccination. The aim of this analysis was to assess whether there are modifying factors that may potentially influence the clinical efficacy of COVID-19 vaccines. A quantitative synthesis of data from Phase III trials was performed via pairwise and network meta-analyses, along with meta-regression analysis. Data from Phase III trials are currently available only for AZD1222, BNT162b2, mRNA-1237, and Sputnik V. Vaccination resulted to be generally effective (90.0%, 95%CI 72.6-96.4; p < 0.001), although the efficacy of AZD1222 (62.1%) introduced a significant level of heterogeneity in the meta-analysis (I-2 92.17%, p < 0.001). No significant modifying factors resulted from the meta-regression analysis. However, considering the mRNA-based vaccines, a trend toward significance (p = 0.081) resulted for age. The network meta-analysis provided the following rank of effectiveness: BNT162b2 similar or equal to mRNA-1273 > Sputnik V >> AZD1222. In conclusion, no modifying factors seem to modulate the efficacy of vaccines against COVID-19. This quantitative synthesis will need to be updated as soon as further clinical results on the efficacy profile are available from Phase III trials for further licensed COVID-19 vaccines.