Vaccine effectiveness against influenza A in older adults and the effect of chronic conditions: Results from the I-MOVE and VEBIS multicentre European hospital case–control studies, 2015/16–2023/24

Background The Influenza – Monitoring Vaccine Effectiveness (I-MOVE/I-MOVE+) and the 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) against influenza (sub)types since 2015/16. We aimed to measure the effect of chronic conditions on influenza A subtype VE among older adults (≥65 years) using pooled-season data from 2015/16 to 2023/24. Methods Hospital teams swabbed severe acute respiratory infection (SARI) patients within 7 days of 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 those with none, one or at least two chronic conditions and by each 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 (2016/17–2019/20, 2022/23, 2023/24), and 2590 A(H3N2) cases with 14,920 controls (2015/16, 2017/18–2019/20, 2022/23, 2023/24) from 13 study sites in 12 countries. Over these seven seasons, >60% cases and 70% controls had at least two 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 none, one and two or more chronic conditions. Most IVE point estimates by chronic condition 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 none, one and two or more chronic conditions. Here, IVE point estimates by chronic condition ranged 13–25%, apart from immunosuppression (5%), kidney disease (6%) and liver disease (31%), but again, 95% CIs overlapped. There were no significant interactions. Conclusions Pooled-season results suggest low–moderate VE against influenza A subtypes among SARI patients ≥65 years, higher against A(H1N1)pdm09 than against A(H3N2), with little evidence of modifying effect of most chronic conditions, 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.