Acute Severity Versus Long-term Morbidity: Uncoupling the Roles of RSV and HRV in Childhood Respiratory Disease

The distinct roles of respiratory syncytial virus (RSV) and human rhinovirus (HRV) in acute illness and subsequent asthma remain debated. China's strict nonpharmaceutical interventions (NPIs) in 2022 provided a unique epidemiological setting to compare their clinical/inflammatory profiles and associations with long-term asthma risk.

This observational retrospective cohort study included children hospitalized with RSV- or HRV-induced acute lower respiratory tract infections. We collected clinical data, subtyped RSV samples and conducted long-term follow-up to assess physician-diagnosed asthma using Kaplan-Meier and multivariable logistic regression.

Among 722 children (425 RSV, 275 HRV, and 22 coinfection), RSV predominated in infants with a sharp winter peak (RSV-A dominant, 96.8%), while HRV circulated year-round across a broader age range. RSV infection was associated with greater acute severity, including higher rates of pneumonia and longer hospitalization (P < .05). In contrast, HRV triggered a distinct inflammatory response with significant leukocytosis and an eosinophil count over 4-fold greater than the RSV group (P < .001). Follow-up revealed HRV infection was independently associated with increased risk of subsequent asthma (log-rank P < .001). Multivariable regression identified prior wheezing (aOR 2.82, 95% CI: 1.76-4.53), elevated eosinophils (aOR 2.43, 95% CI: 1.07-5.49), and HRV infection (aOR 1.85, 95% CI: 1.15-2.99) as independent predictors for asthma.

During China's late NPI phase, HRV infection showed a stronger independent association with childhood asthma than RSV. This association, together with an eosinophil-predominant inflammatory profile, remained significant after adjustment for prior wheezing history. These findings should be interpreted as associations rather than evidence of causality.