Performance comparison between heterologous and homologous COVID19 vaccine schedules on Omicron variant incidence: A real-world retrospective cohort study in Southern Italy.

As the COVID19 pandemic progresses, there is an increasing need to evaluate the performance of vaccine strategies. This study investigated the vaccine schedule performance of heterologous vaccination compared to homologous vaccination in preventing Omicron SARS-CoV2 infection in the adult population. This retrospective cohort study utilized data from the Infections Regional Information System and the Apulia Regional Vaccine Registry to identify individuals who received a booster dose of one of 14 different COVID19 vaccination schedules between September 2021 and August 2022 in the province of Lecce, Southern Italy. The standardized cumulative incidence of SARS-CoV2 infection after the booster dose was assessed and the risk of infection between subgroups of heterologous and homologous vaccination schedules was compared using the Cochran-Mantel-Haenszel test. A total of 469,069 subjects were included in the study. The standardized incidence of SARS-CoV2 infection varied greatly among different vaccine schedules, with the highest and lowest being AZ-AZ-BNT (34.7 %) and MOD-MOD-BNT (18.9 %), respectively, and some heterologous schedules performing better than homologous ones. The risk of SARS-CoV2 infection was significantly lower in individuals who received specific heterologous vaccination schedules compared to homologous vaccination schedules, the best performing being MOD-MOD-BNT with a common odd ratio of 0.661 (IC. 95 % [0.620-0.704]). This study provides evidence that heterologous vaccination schedules may be more effective in preventing Omicron SARS-CoV2 infection compared to homologous vaccination schedules, highlighting how the vaccine product, rather than the platform, is involved in the different protection provided by heterologous vaccination.