Clinical Insights and Severity of Enterovirus D68 Respiratory Infections in Vietnamese Children.

Background: Enterovirus D68 (EVD68) causes respiratory disease, yet the risk of severe respiratory disease remains incompletely quantified, especially when stratified by comorbidity status. This study aims to describe the clinical features and risk of severe disease in children with EVD68 compared with those with other Rhinoviruses/Enteroviruses, accounting for comorbidity. Methods: We analyzed 1100 pediatric EV-positive cases from surveillance in Vietnam (2019-2022), excluding viral coinfections. EVD68 was confirmed by real-time PCR. We examined clinical features, treatments, and comorbidities. Standardization methods estimated risk differences (RDs) and risk ratios (RRs) stratified by (1) general comorbidity, (2) asthma, and (3) either of these. Time-to-recovery in intensive care unit (ICU) was compared using Kaplan-Meier methods. Results: EVD68 was detected in 55/1100 cases (5.0%). Children with EVD68 more often had wheeze, pneumonia, oxygen therapy, and ICU admission. For wheeze, EVD68 was associated with similar elevated risk with and without general comorbidity (RR 1.40 in both; RD 0.27). Pneumonia risk was likewise elevated with EVD68 (with comorbidity: RR 1.17; RD 0.12; without: RR 1.73; RD 0.14). By asthma status, EVD68 increased wheeze risk in both groups; however, the excess was smaller in asthma (RR 1.10; RD 0.09) than non-asthma (RR 1.43; RD 0.29), consistent with baseline wheeze susceptibility in asthma. Pneumonia risk was similar regardless of asthma status. During ICU stay, wheeze persisted longest in both groups. Time-to-recovery was similar between groups. Conclusions: EVD68 infection was associated with a higher risk of severe disease than Rhinoviruses/Enteroviruses, independent of documented comorbidity, indicating substantial risk even among previously healthy children.