Clinical Characteristics of Enterovirus D68 Respiratory Disease in Colorado Children Over a Decade: 2014-2025

BACKGROUND: Enterovirus D68 (EV-D68) causes cyclical outbreaks worldwide. Though EV-D68 can rarely cause acute flaccid myelitis, it commonly causes respiratory disease. In particular, EV-D68 causes outbreaks of severe asthma-like respiratory disease, but few systems have the capability to detect EV-D68 cases. METHODS: Active, prospective EV-D68 surveillance at Children's Hospital Colorado has been performed since 2014, where a random subset of residual clinical respiratory specimens, primarily from inpatient settings, and positive for rhinovirus/enterovirus are tested for EV-D68 via reverse transcription-polymerase chain reaction. Data via chart review from this surveillance were analyzed from 2014 to 2025 to characterize the clinical characteristics of EV-D68 respiratory disease in children (<18 years). RESULTS: From 2014 to 2025, EV-D68 was detected in 308 patients, of which 271/308 (88%%) were children with respiratory disease. Median age of children with respiratory disease was 6 [interquartile range (IQR): 3.1-10.4] years; 162/271 (59.8%) were males. A majority of children admitted required intensive care unit admission (206/258, 79.8%). Though only 174/271 (64.2%) children had an atopic history, a significant majority required bronchodilator therapy (249/271, 91.9%) and systemic steroids (229/271, 84.5%). Median intensive care unit and hospital length of stay were 2 (IQR: 1-3) and 3 (IQR: 2-5) days, respectively. CONCLUSIONS: Children with EV-D68 respiratory disease commonly presented with severe asthma-like respiratory disease, even in those without atopy. Despite the severity of disease, children quickly improved over short hospitalizations when managed with bronchodilators, steroids, and respiratory support. With improved diagnostics to detect and recognize the true burden of EV-D68, additional studies evaluating short- and long-term management of EV-D68 respiratory disease are needed.