Real-world comparative effectiveness of SARS-CoV-2 primary vaccination campaigns against SARS-CoV-2 infections: a federated observational study emulating a target trial in three nations.

Publication date: Jan 07, 2026

To assess the impact of large-scale severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination campaigns in real-world settings across regions, we performed a reproducible cross-border comparison of the real-world effectiveness of primary vaccination in preventing SARS-CoV-2 infections across three sites: Aragon (Spain), Brussels and Wallonia (Belgium), and Finland. This observational study emulated a target trial by daily matching primary vaccinated individuals 1:1 to un- or partially vaccinated individuals using propensity scores estimated on a set of relevant confounders from January to September 2021. Matched individuals were followed up until a SARS-CoV-2 infection was contracted or a censoring event occurred. Vaccine effectiveness in preventing infections was estimated by the difference in restricted mean survival time (RMST). Primary vaccination extended the average free-of-infection time by 35. 9 [95% confidence interval (CI) (34. 9-37. 0)], 59. 6 [95% CI (59. 3-60. 0)], and 1. 6 [95% CI (1. 1-2. 0)] days over 365 days in the population cohort of Aragon (Spain), Brussels and Wallonia (Belgium), and Finland, respectively. This federated population-based observational study showed the effectiveness of the SARS-CoV-2 primary vaccination campaign in prolonging the mean time to infection in the Aragon (Spain) and Brussels and Wallonia (Belgium) population cohorts. Only a minor difference over this time frame was found in Finland’s population cohort.

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Original Article