Introduction: Rhinoviruses (RVs) are well-known trigger of wheezing episodes in children with asthma. Their role in other pediatric chronic medical conditions is not fully know. Methods: Patients ≤21 years hospitalized or evaluated as outpatients with symptomatic RV infection were identified from 2011-2013. Patients were categorized based on the type of underlying disease and differences in clinical parameters, RV loads (CT values), viral and bacterial coinfections and clinical outcomes compared between groups. Multivariable analyses were performed to identify the comorbidities associated with oxygen requirement, PICU admission, and prolonged hospitalization. Results: Of 1,899 children analyzed, 77.7% (n=1477) had an underlying comorbidity including asthma (36.8%), prematurity (7.7%), chronic respiratory diseases (6.4%), congenital heart disease (CHD, 3.2%), immunocompromised hosts (ICH; 1.4%) and others (22.2%). Prevalence of comorbidities increased with age (70%, infants vs 84%-87%, children >1 year; p<0.0001). Median RV loads were intermediate-high (24-26 CT values), irrespective of the underlying disease. RV/ viral co-detections were identified in 11% of ICH vs 20%- 30% in all other children while bacterial co-infections were identified in 2.9% of children. Multivariable models identified asthma, prematurity, CHD and bacterial coinfections consistently associated with all three clinical outcomes (p<0.0001). Older age and higher RV loads were also associated with increased odds of PICU admission.   Conclusions: The prevalence of comorbidities was high in children with RV infections. Of those, asthma, prematurity and CHD were consistently associated with severe disease. Bacterial co-infections and higher RV loads further predicted worse clinical outcomes, highlighting the importance of identifying clinical phenotypes for future targeted interventions.

I have read the journal's policy and the authors of this manuscript have the following competing interests: AM has received fees for participation in Advisory Boards from Janssen, Merck, Pfizer, Moderna, Enanta, AstraZeneca and Sanofi-Pasteur and grants from NIH, Merck and Janssen to institution. OR has received fees for participation in Advisory Boards from Merck, Pfizer, AstraZeneca and Sanofi-Pasteur and grants from NIH, Bill & Melinda Gates Foundation, Merck and Janssen to institution. ALL has received research grants from BioFire, Cepheid, Luminex, and Diasorin, and consulting fees from Medscape, Biorad and BioFire. The remaining authors have no conflicts of interest.

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