COVID-19 vaccine effectiveness against SARS-CoV-2-confirmed hospitalisation in the eastern part of the WHO European Region (2022-2023): a test-negative case-control study from the EuroSAVE network

Background: Understanding COVID-19 vaccine effectiveness (VE) in preventing severe disease is critical to inform vaccine policy. We used the test-negative design to estimate VE against SARS-CoV-2-confirmed hospitalisation in adults ≥18 years in the eastern WHO European Region.

Methods: We included patients hospitalised for severe acute respiratory infection (SARI) at sentinel surveillance sites in Albania, Georgia, Kyrgyzstan, North Macedonia, Serbia, and in Kosovo. We collected demographic information, COVID-19 vaccination history, and tested respiratory samples for SARS-CoV-2 by RT-PCR. We calculated VE of any vaccine dose received within 12 months (Annual VE) as [(1 - adjusted Odds Ratio) x 100%] using a one-stage pooled analysis. The reference group included unvaccinated individuals and those who received their last vaccine >12 months before symptom onset.

Findings: During 1 January 1, 2022-November 20, 2023, of 5162 patients, 57.0% (2942) were unvaccinated, 2.5% (129) received only one dose, 26.0% (1340) received only two doses (originally considered a primary series vaccine (PS)), 13.2% (683) received three doses only, and 1.3% (68) received four doses. Most PS vaccines and boosters were BNT162b2 (46.4% (622/1340) and 64.9% (443/683), respectively) and CoronaVac (23.0% (309/1340) and 18.3% (125/683)). No patients received Ad26.COV2.S (Johnson and Johnson) vaccines. Overall, 1009/5162 (19.5%) patients were SARS-CoV-2-positive. VE was 60.1% (95% Confidence Interval (CI) 12.4-81.8) for last vaccine received 14-89 days before symptom onset, 60.0% (95% CI 32.2-76.4) for 90-179 days, 7.0% (95% CI -28.5 to 32.7) for 180-269 days, and -5.4% (95% CI -43.8 to 22.8) for 270-365 days.).

Interpretation: During nearly two years of Omicron circulation in the eastern WHO European Region, COVID-19 vaccination reduced the risk of hospitalisations by more than half for 6 months following vaccination.

Funding: This study was funded by the World Health Organization, Regional Office for Europe through a cooperative agreement with the U.S. Centers for Disease Control and Prevention.