Selection criteria and definitions
We included individuals aged between 65 and 110 years (inclusive). We excluded residents in long-term-care facilities (using the last available information) and early vaccinees (defined as either being vaccinated before recommended for their age group or the first 5% vaccinated of each 5-year age band) to exclude vulnerable groups with different probabilities of vaccination and developing severe COVID-19. In addition, we excluded those with inconsistent data on vaccination (two-dose primary vaccination with <19 days apart, or those vaccinated with a booster <90 days after the last primary or booster dose, or a combination of brands other than recommended in the EU/EAA). Individuals with a previously recorded positive SARS-CoV-2 test (previous infection) were excluded until April 2022, but not thereafter.
Outcomes of interest were: 1) hospitalisation due to COVID-19, defined as admission to a hospital with a SARS-CoV-2 infection laboratory-confirmed from 14 days before to one day after admission, in which admission criteria are compatible with a severe acute respiratory infection , or in which COVID-19 is the main diagnosis in the discharge record, and 2) COVID-19-related death, defined as death for which COVID-19 is recorded as the cause of death or, if the cause of death is not available, laboratory-confirmed SARS-CoV-2 infection with death in the 30 days after the positive test or symptom onset.
For each outcome, we assumed the date of the positive test result (i.e. the date of the first SARS-CoV-2 positive test of the infection episode that resulted in hospital admission or death) as the date of the outcome.
The vaccination status was defined as a time-varying variable within each observation period and classified as: 1) unvaccinated (no record of COVID-19 vaccine administration); 2) complete primary vaccination, if received one dose of Jcovden® or two doses of any combination of Comirnaty®, Spikevax® or Vaxzevria®; 3) vaccination with the first booster, if received an additional dose of Comirnaty®, Spikevax® (monovalent or bivalent) at least 90 days after the complete primary vaccination; 4) vaccination with the second booster, if received a first booster and an additional dose of Comirnaty®, Spikevax® (monovalent or bivalent) at least 90 days later; 5) vaccination with the third booster, defined in the same way as the second booster.
Analytical methods for site-specific vaccine effectiveness