BACKGROUND: The Influenza - Monitoring Vaccine Effectiveness in Europe (I-MOVE/I-MOVE+) and Vaccine Effectiveness, Burden and Impact Studies (VEBIS) hospital networks have conducted seasonal multicentre, test-negative, case-control studies in Europe to measure influenza vaccine effectiveness (IVE) since 2015/16. We measured the effect of chronic conditions on VE of influenza A subtypes among older adults (≥ 65 years) using pooled-season data (2015/16-2023/24). METHODS: Hospital teams swabbed patients with severe acute respiratory infection (SARI) within 7 days of symptom onset. Cases were RT-PCR positive for influenza A(H1N1)pdm09 or A(H3N2); controls negative for any influenza virus. We calculated overall pooled-season IVE against influenza A(H1N1)pdm09 and A(H3N2), adjusted for study site, sex, age and onset date; and stratified by number of and by each chronic condition (diabetes, heart disease, lung disease/asthma, immunosuppression, kidney disease, liver disease, cancer, obesity). We investigated interaction between vaccination and each condition. RESULTS: We included 1805 A(H1N1)pdm09 cases with 16,329 controls; 2590 A(H3N2) cases with 14,920 controls, from 13 study sites (12 countries). Over all seasons, 63-67% cases and 70% controls had ≥ 2 chronic conditions. Against A(H1N1)pdm09, pooled-season IVE was 37% (95%CI: 29-44) overall; 49% (95%CI: 9-72), 30% (95%CI: 12-44) and 38% (95%CI: 29-46) in those with 0, 1, ≥ 2 chronic conditions. Most IVE point estimates were 34-45%, apart from immunosuppression (-7%), kidney disease (17%) and liver disease (54%), but 95% CIs overlapped. Significant interaction was observed for kidney disease (p = 0.02) and immunosuppression (p = 0.01). Against A(H3N2), pooled-season IVE was 17% (95%CI: 8-25) overall; 15% (95%CI: -26-42), 11% (95%CI: -8-27) and 18% (95%CI: 7-28) in those with 0, 1, ≥ 2 chronic conditions. Here, IVE point estimates ranged 13-25%, apart from immunosuppression (5%), kidney disease (6%) and liver disease (31%), although 95% CIs overlapped. There were no significant interactions. CONCLUSIONS: Pooled-season results suggest low-moderate VE against influenza A subtypes among older SARI patients; higher against A(H1N1)pdm09 than A(H3N2), with little evidence of chronic condition modifying effect, apart from kidney disease and immunosuppression. We stress the importance of developing improved influenza vaccines for specific populations, and encourage further research into the effect of chronic conditions on IVE in older adults.

Cantacuzino National Medical Military Institute for Research and Development Bucharest Romania

Centre for Infectious Disease Control National Institute for Public Health and the Environment Bilthoven the Netherlands

Clinic of Infectious Diseases and Dermatovenerology Institute of Clinical Medicine Faculty of Medicine Vilnius University Vilnius Lithuania

Croatian Institute of Public Health Zagreb Croatia

Department for Infectious Disease Epidemiology Robert Koch Institute Berlin Germany

Department of Child and Adolescent Health Mater Dei Hospital Msida Malta

Department of Infectious Diseases Istituto Superiore di Sanità Rome Italy

Department of Infectious Diseases Lithuanian University of Health Sciences Kaunas Lithuania

Department of Infectious Diseases Université Libre de Bruxelles CHU Saint Pierre Brussels Belgium

Epiconcept Paris France

Epidemiology Department National Health Institute Doutor Ricardo Jorge Lisbon Portugal

European Centre for Disease Prevention and Control Stockholm Sweden

Health Service Executive Health Protection Surveillance Centre Dublin Ireland

Infectious Disease Prevention and Control Unit Health Promotion and Disease Prevention Msida Malta

INSERM CIC 1417 F CRIN 1 REIVAC Network Assistance Publique Hôpitaux de Paris Hôpital Cochin Paris France

Institute of Public Health Tirana Albania

Instituto de Salud Pública de Navarra IdiSNA CIBERESP Pamplona Spain

National Centre of Epidemiology CIBERESP Institute of Health Carlos 3 Madrid Spain

National Centre of Microbiology CIBERESP Institute of Health Carlos 3 Madrid Spain

National Institute of Public Health NIH National Research Institute Warsaw Poland

National Laboratory for Health Security Epidemiology and Surveillance Centre Semmelweis University Budapest Hungary

National Reference Centre for Influenza Robert Koch Institute Berlin Germany

Public Health Scotland Glasgow Scotland

Research Group on Difficult to Diagnose and Treat Infections IIS Aragón Miguel Servet University Hospital Saragossa Spain

Sciensano Brussels Belgium

Université Paris Cité Paris France

University Hospital Brno and Masaryk University Brno Czechia

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