Study design and setting
Using a common protocol , Belgium, Denmark, Luxembourg, Navarre (Spain), Norway and Portugal constructed population cohorts based on data collected routinely in EHR. Countries were recruited based on their assessed capability to join the study and a formal outreach performed by the ECDC. We used individual deterministic linkage to cross-match administrative population and statistical office databases with registers for COVID-19 vaccination, SARS-CoV-2 testing, hospitalisations, deaths and clinical data. Belgium was unable to include unvaccinated individuals, but followed the same protocol to compare individuals with different vaccination status to provide relative VE (rVE) estimates. A description of the EHR used by each study site to monitor COVID-19 VE is provided in the supplementary material (Supplementary material, Appendix 1).
We estimated COVID-19 VE with monthly frequency. For each month, the observation period covered eight weeks to allow sufficient events to provide precise estimates and to be sensitive to changes in VE over time. Overall, the observation period was between October 2021 and November 2022. Between October 2021 and March 2022, we piloted a common protocol for an outcome of COVID-19 hospitalisation in four study sites: Denmark, Navarre (Spain), Norway, and Portugal . From March 2022 onwards, we added the outcome of COVID-19-related death, from April 2022 onwards, we added rVE estimates and, from June 2022 onwards, we added two study sites (Belgium and Luxembourg).