Effectiveness of Seasonal Influenza Vaccination Against Medically Attended Influenza in People With Chronic Respiratory Diseases: A Multicenter, Test-Negative, Case-control Study

Background Patients with chronic respiratory disease (CRD) face an increased risk of severe influenza complications. However, limited studies offer estimates of vaccine effectiveness (VE) against influenza within these CRD populations in China. Methods A multicenter, retrospective, test-negative, case-control study was conducted to estimate the VE in 37 medical institutions in Shanghai, China, during the 2023/2024 and 2024/2025 seasons. We included patients with CRD who presented with acute respiratory infections and received nucleic acid amplification tests and/or rapid antigen tests. Patients with CRD with a positive test were assigned to the case group, and those with a negative test were assigned to the control group. Multivariable unconditional logistic regression was used to control potential confounders and to determine 95% confidence intervals (CIs). Results A total of 10 711 participants, including 1650 influenza cases (5.8% vaccinated) and 9061 influenza-negative controls (7.9% vaccinated), were eligible for analysis. The combined VE over the 2 seasons was estimated to be 44.23% (95% CI: 30.45-55.75) for the study population. The VE was 42.91% (95% CI: 27.13–55.78) in the 2023/2024 season and 51.51% (95% CI: 17.70–73.61) in the 2024/2025 season. The combined VE for influenza subtypes A and B were 38.49% (95% CI: 21.75–52.27) and 62.64% (95% CI: 39.91–78.28), respectively. Conclusions Influenza vaccination provides consistent and moderate protection to patients with CRD against medically attended influenza, regardless of the dominant circulating subtypes. Nevertheless, vaccination coverage remains suboptimal, underscoring the need to improve annual influenza vaccination uptake among patients with CRD , even amid ongoing viral antigenic evolution through shifts and drifts.