Severity and Cost of Respiratory Syncytial Virus Versus Influenza in Hospitalized Adults in Spain

ABSTRACT Background Respiratory syncytial virus (RSV) can lead to severe outcomes, particularly in older and vulnerable adults, yet it remains underdiagnosed due to limited testing. This study compared the severity and costs of laboratory‐confirmed RSV versus influenza hospitalizations. Methods We performed a retrospective analysis using data from the Valencia Hospital Network for the Study of Infectious Diseases (VAHNSI), covering up to 46% of the Valencia Region's population. Hospitalized influenza‐like illness (ILI) cases in individuals aged ≥ 65 years across six seasons (2014/15–2019/20) were included. RSV and influenza were identified by multiplex RT‐PCR. Outcomes assessed included mechanical ventilation (MV), hospital length of stay (LOS), in‐hospital death, 30‐day post‐discharge death, and hospitalization costs. Logistic and log‐normal regression models were used to compare severity and cost outcomes between RSV and influenza, adjusting for age, sex, comorbidities, and influenza vaccination status. Odds ratios (ORs) and mean ratios (MRs) with 95% confidence intervals (CIs) were calculated. Results Of 1954 hospitalizations, 429 (22%) were due to RSV and 1525 (78%) to influenza. RSV cases showed higher MV use (9.26% vs. 4.15%; adjusted OR 2.43 95% CI: 1.61–3.67) and longer LOS (7.7 vs. 6.8 days; adjusted MR 1.10 95% CI: 1.02–1.19). Mortality outcomes were similar. RSV hospitalizations incurred 6% higher mean costs (€3907 vs. €3806). Conclusions RSV hospitalizations in older adults were less frequent but more severe and costly than influenza, with comparable mortality. These findings highlight the importance of RSV prevention and support the development of targeted vaccination programs for the elderly.