Multi-Year Analysis of Respiratory Viral Dynamics Reveals Significance of Rhinovirus in Young Children with Severe Respiratory Illness.

: We aimed to analyze the landscape of viral respiratory illnesses (VRIs) in a large metropolitan area in Southern California with a focus on the COVID-19 pandemic. : We conducted a retrospective cohort study within the UCLA Health System, which evaluated children aged 0-5 years who received comprehensive respiratory viral panel (cRVP) testing during August-February of 2018-2023. The patient demographics, disease severity, and clinical course were specifically compared during the pandemic. Predictors of significant VRI were determined by multivariate logistic regression. : A total of 1321 children underwent cRVP testing, and 753 positive subjects were identified during the study period. Rhinovirus (RV) was by far the most frequent virus detected across 5 years, even during the COVID-19 pandemic, followed by respiratory syncytial virus (RSV). Along with RSV and human metapneumovirus, RV was identified as an independent risk for significant disease and occurred irrespective of co-infection with other viruses. : RV was the most common viral pathogen in young children, even during the height of the COVID-19 pandemic, and was an independent driver of moderate-to-severe disease, particularly in children with comorbidities. Ethnic disparities were also observed as a risk for significant disease, underscoring the need for targeted interventions and heightened clinical vigilance in pediatric populations.