Burden of respiratory syncytial virus and influenza in adults – a Danish nationwide cohort study

Objectives Like influenza, respiratory syncytial virus (RSV) is a common cause of severe acute respiratory infection (ARI) in adults. With RSV vaccines recently approved, data on the burden of disease are required. Our objective was to investigate the short- and long-term clinical and economic burden of ARI in Danish adults over the past decade, with a primary focus on RSV, contextualising with influenza. Methods A nationwide cohort study in Denmark, including adults ≥18-year-old recorded with an ARI from 1 July 2011 to 30 June 2022 (i.e. exposed), matched 1:3 with individuals without ARI (unexposed). We assessed adverse clinical outcomes, direct and indirect healthcare resource utilization, and direct and indirect costs over 365 days after ARI. Results We identified 762 443 ARIs, of which 5289 were attributed to RSV and 48 047 to influenza. Common comorbidities in patients with RSV were chronic obstructive pulmonary disease (23.9%, 1264/5289), diabetes (13.5%, 712/5289), and asthma (12.2%, 647/5289), whereas 32.1% (1700/5289) were immunocompromised. RSV was associated with an increased risk of adverse clinical outcomes compared with matched unexposed individuals during the 365-day follow-up, including death (relative risk 2.7; 95% CI: 2.4–3.0), chronic obstructive pulmonary disease exacerbations (3.1; 2.8–3.4), asthma exacerbations (4.6; 3.6–5.9), and sepsis (4.0; 3.1–5.2). RSV was associated with increased risks of respiratory support (5.5; 4.3–7.0) and antibiotic treatment (2.0; 1.9–2.1). Direct and indirect costs were higher among patients with RSV than their unexposed peers, with a mean difference in direct costs of €12 096. Patients with influenza had fewer comorbidities than patients with RSV, but they also presented worse clinical and economic outcomes than their unexposed peers, with a mean difference in direct costs of €7992. Conclusions The severe long-term clinical and economic burden of RSV in adults, which is comparable with influenza, provides evidence for adult vaccination strategies.