Excess mortality and hospitalisations associated with respiratory syncytial virus, influenza, and COVID-19 among adults in Denmark (2015–2024): a modelling study

Background: Understanding the long-term epidemiology trends of RSV, influenza, and COVID-19 is essential for planning of vaccination strategies and healthcare system epidemic preparedness. This is the first study to provide a comprehensive estimation of both excess mortality and hospitalisations among adults for these respiratory viruses in a European setting. We aim to estimate excess mortality and excess hospitalisations for RSV, influenza, and COVID-19 among adults ≥18 years in Denmark from January 2015 to March 2024. Methods: This nationwide time-trend modelling study investigates weekly mortality and hospitalisation rates surpassing the seasonal baseline for RSV, influenza, and COVID-19 among adults in Denmark. Data from the Cause of Death Register, the Danish National Patient Registry, and respiratory virus surveillance data were analysed with Generalized Additive Models (GAM) using a negative binomial likelihood function, including RSV, influenza, COVID-19 variants, and time effects to account for seasonality and trend. Findings: We estimated 3944 RSV-attributed, 5675 influenza-attributed, and 5636 COVID-19-attributed deaths. Among adults aged 65 or older, the annual mortality rates were 31.2 per 100,000 for RSV, 42.9 for influenza, and 88.5 for COVID-19. Furthermore, we estimated annual admission rates for those aged 65 and older of 177.4 per 100,000 for RSV, 164.6 for influenza, and 398.7 for COVID-19. Interpretation: This modelling study reveals a substantial impact of RSV on individuals aged 65 and older, with a notable increase in RSV-attributed deaths and hospitalisations in recent years likely due to expanded respiratory testing after the COVID-19 pandemic. Our findings highlight the need for increased awareness in previously considered lower-risk patients, and establish benchmarks for evaluating preventive interventions. Funding: This study received funding from Independent Research Fund Denmark.