Severity of respiratory syncytial virus versus SARS-CoV-2 Omicron and influenza infection amongst hospitalized Singaporean adults: a national cohort study

Background: More data is required to contextualise respiratory-syncytial-virus (RSV) disease burden, versus other vaccine-preventable respiratory-viral-infections (RVIs) in older adults. We aimed to compare severity of RSV in hospitalized adults versus influenza/boosted COVID-19. Methods: Retrospective population-based cohort study, including all adult RSV hospitalizations (2021-2023) in Singapore. Disease severity (28-day mortality/intensive-care-unit [ICU] admission) and healthcare utilization in RSV hospitalizations were compared with contemporaneous influenza hospitalizations and COVID-19 hospitalizations in 2023. Outcomes for COVID-19 were stratified by type/receipt of boosters. Comparative severity of RSV versus COVID-19/influenza was evaluated using multivariate logistic regression, adjusted for confounders. Generalized linear models were utilized to estimate excess length-of-stay/costs of RSV hospitalization versus COVID-19/influenza as a rate-ratio. Findings: 12,811 hospitalized adults were included (RSV: N = 1332; influenza: N = 3999; COVID-19: N = 7480). Amongst RSV hospitalizations, 5.4% (72/1332) died within 28 days; 3.8% (51/1332) required ICU. Median length-of-stay (RSV) was 5.0 days (IQR = 3.0-8.0). Older age/diabetes were associated with greater odds of 28-day mortality in RSV hospitalizations. Higher odds of 28-day mortality/ICU admission and higher healthcare utilization was observed in RSV hospitalizations versus influenza. Conversely, RSV was less severe than unboosted COVID-19, with lower odds of 28-day mortality (adjusted-odds-ratio, aOR = 0.56 [95% CI = 0.40-0.79]) and rate-ratio for length-of-stay/costs significantly <1. However, higher odds of ICU (aOR = 1.80 [95% CI = 1.07-3.00]) were observed in RSV hospitalizations, versus COVID-19 hospitalizations boosted <1 year prior with updated vaccines. Interpretation: Hospitalizations attributed to RSV were more severe than influenza. RSV disease was less severe versus COVID-19 in unboosted patients but severity was not significantly different from COVID-19 in boosted individuals. Funding: National Medical Research Council, Singapore.