Effectiveness of influenza vaccination in preventing severe COPD exacerbations and pneumonia before, during, and after the COVID-19 pandemic: a retrospective cohort study.

Background: Influenza vaccination is recommended to reduce complications and hospitalisations in individuals with COPD. Recent fluctuations in COPD-related hospitalisations underscore the need to evaluate vaccine effectiveness in preventing severe exacerbations and pneumonia across pre-, during-, and post-COVID-19 periods. Methods: We conducted a retrospective cohort study of Clalit Health Services members with COPD, comparing influenza-vaccinated individuals to matched unvaccinated controls. To reduce bias, we matched vaccinated individuals with unvaccinated controls across 648 subgroups by age, sex, exacerbation history, comorbidities, and vaccination tendency. The primary outcome was hospitalisation for exacerbations or pneumonia during each influenza season (2017-2024), categorised into pre- (2017-2020), during (2020-2022), and post-COVID-19 (2022-2024) periods. We defined each influenza season based on weekly surveillance data reporting influenza circulation, ensuring that comparisons accurately corresponded to the actual periods of influenza virus activity. Subgroup analyses stratified participants by low or high risk based on prior-year exacerbations. Findings: Among 88,446 COPD patients, severe exacerbations and pneumonia decreased by 20% during the COVID-19 pandemic (2020-2022) but returned to baseline post-pandemic (2022-2024). Vaccine effectiveness in reducing these outcomes was 30% (95% CI: 24-35%) pre-pandemic (2017-2020) but was limited during the pandemic (10%, 95% CI: -5 to 22%) and post-pandemic (-2%, 95% CI: -15 to 8%). High-risk individuals, representing 30% of the COPD population, accounted for over 85% of cases, with vaccine effectiveness showing similar trends across risk groups. Interpretation: While influenza vaccination remains recommended to reduce complications associated with influenza, its effectiveness in preventing severe exacerbations or pneumonia may be limited during and after the COVID-19 pandemic in individuals with COPD. Additional preventive measures, such as social distancing, should be integrated into public health efforts, especially during periods of heightened respiratory infection circulation and for high-risk individuals. Funding: This work was supported by the European Research Council, project #949850 and the Israel Science Foundation (ISF), grant No. 3409/19, within the Israel Precision Medicine Partnership program.