Molecular and Clinical Comparison of Enterovirus D68 Outbreaks Among Hospitalized Children, Ohio, USA, 2014 and 2018

Huanyu Wang; Alejandro Diaz; Katherine Moyer; Maria Mele-Casas; Maria Fatima Ara-Montojo; Isabel Torrus; Karen McCoy; Asuncion Mejias; Amy L. Leber


Emerging Infectious Diseases. 2019;25(11):2055-2063. 

In This Article

Abstract and Introduction


Enterovirus D68 (EV-D68) causes respiratory tract infections and neurologic manifestations. We compared the clinical manifestations from 2 EV-D68 outbreaks in 2014 and 2018 and a low-activity period in 2016 among hospitalized children in central Ohio, USA, and used PCR and sequencing to enable phylogenetic comparisons. During both outbreak periods, infected children had respiratory manifestations that led to an increase in hospital admissions for asthma. The 2018 EV-D68 outbreak appeared to be milder in terms of respiratory illness, as shown by lower rates of pediatric intensive care unit admission. However, the frequency of severe neurologic manifestations was higher in 2018 than in 2014. During the same period in 2016, we noted neither an increase in EV-D68 nor a significant increase in asthma-related admissions. Phylogenetic analyses showed that EV-D68 isolates from 2018 clustered differently within clade B than did isolates from 2014 and are perhaps associated with a different EV-D68 subclade.


Enterovirus D68 (EV-D68) was originally identified in 1962 in children with severe respiratory tract infections in California, USA.[1] The virus shares biological features with enteroviruses and rhinoviruses and was reported sporadically after these initial reports.[2] However, EV-D68 gained epidemiologic and clinical relevance in 2014 after it was identified as an important pathogen associated with severe lower respiratory tract infections and, in some cases, with central nervous system disease (i.e., acute flaccid myelitis [AFM]).[3–5]

Nationwide Children's Hospital (NCH) in Columbus, Ohio, USA, experienced a first outbreak of EV-D68 in 2014 that was associated with respiratory distress and disproportionately affected children with asthma; no case of AFM was identified.[3] Although EV-D68 reportedly has a biennial seasonality, NCH did not have an EV-D68 outbreak in 2016. EV-D68 emerged again in 2018 and caused respiratory infections and, in some cases, neurologic manifestations.

The objective of this study was to compare differences in clinical characteristics and disease severity among children hospitalized with EV-D68 infection at NCH in 2018 with those identified during the 2014 outbreak and during a low-activity period (2016). We also sought to define the overlap between EV-D68 circulation and hospitalizations for asthma and compare the sequence variation of EV-D68 strains identified during the 2018 outbreak with strains identified in previous years.