Objectives To compare the clinical characteristics and outcomes of patients hospitalized with respiratory syncytial virus (RSV), human metapneumovirus (hMPV), and influenza infections. Methods This study prospectively enrolled 594 patients hospitalized with influenza-like illness (ILI) and laboratory-confirmed RSV, hMPV, or influenza infections over three consecutive influenza seasons at a tertiary hospital in China. Results While certain clinical features were of value as predictors of infection type, none exhibited good predictive performance as a means of discriminating between these three infections (area under the receiver-operating characteristic curve < 0.70). After controlling for potential confounding variables, RSV infections in pneumonia patients were found to be associated with a 30-day mortality risk comparable to that of influenza patients [ () 1.016, () 0.267-3.856, p = 0.982], whereas hMPV infection was associated with a reduced risk of mortality ( 0.144, 0.027-0.780, p = 0.025). Among those without pneumonia, the 30-day mortality risk in patients with influenza was comparable to that in patients infected with RSV ( 1.268, 0.172-9.355, p = 0.816) or hMPV ( 1.128, 0.122-10.419, p = 0.916). Conclusion Disease severity associated with these three types of viral infection was inconsistent when comparing patients with and without pneumonia, highlighting the importance of etiologic testing.

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