Acute respiratory infections (ARI) are a leading cause of morbidity and mortality in pediatric patients [1,2]. Viruses are the most common cause of ARI with rhinovirus (RV), influenza virus, and respiratory syncytial virus (RSV) commonly detected [3]. However, a notable proportion of viral ARI is due to enteroviruses (EV) [4,5]. While EV are generally enterotropic, several EV types cause respiratory infections. The four human EV species (A-D) contain many numbered subtypes, e.g., EV-D68 [6,7].

EV-D68 was first detected from pharyngeal swabs in 1962 and it was initially mistakenly categorized as RV in part due to its predominant respiratory presentation [8]. EV-D68 infections were identified primarily via passive surveillance and only sporadically reported up to 2005 [9,10]. In 2014, the first large U.S. outbreak was reported, soon followed by reports of increased EV-D68 numbers in other countries around the world [11], [12], [13], [14], [15]. Since then, a mostly biennial pattern of circulation has been observed with peaks in the late summer through fall (2014,2016 and 2018). As with other pediatric viral infections, the prevalence of EV-D68 in 2020 was lower than anticipated, likely due to non-pharmacologic mitigation strategies targeted against the SARS-CoV-2 pandemic [16].

EV-D68 can cause severe bronchospasm and status asthmaticus requiring intensive care management, particularly in school-age children [17], [18], [19]. Further outbreaks of acute flaccid myelitis (AFM) occur in parallel with increased community circulation of EV-D68 suggesting a causative relationship exists between EV-D68 and AFM [20], [21], [22]. During the 2014 outbreak, the median age of hospitalized EV-D68 infected children has typically been older (4.6 years) than that of children hospitalized with non-EV-D68 viral infections (2.2 years) [11,12]. Common symptoms of EV-D68 infection involve both the upper respiratory and lower respiratory tract [23]. However, severe EV-D68 infection has been associated with a history of asthma [24]. During previous outbreaks, status asthmaticus recalcitrant to albuterol and steroid treatment were common in asthmatic children infected with EV-D68 [12].

Multiplex molecular assays available in U.S. diagnostic laboratories do not specifically detect EV-D68. Rather, EV-D68 is detected generically being reported among rhinovirus/enterovirus (RV/EV) detections. Therefore, EV-D68 is being detected only if a research assay is employed or samples are sent to public health laboratories. Existing clinical and scientific knowledge gaps about EV-D68 suggest a need for both additional education of practitioners about clinical presentations and for increased EV-D68 surveillance infrastructure. Confirmation of EV-D68 community circulation early during outbreaks could help clinicians and public health groups to be more vigilant for EV-D68-like presentations in their areas, including recalcitrant asthma and AFM.

In July 2022, (a year of likely biennial increase in EV-D68 prevalence), increased generic RV/EV detections in patients with symptoms resembling those in previous EV-D68 outbreaks were noted in Kansas City and other areas, earlier than the usual late summer/early autumn biennial seasonality. This and queries from frontline Kansas City clinicians of potential causes for severe RSV-negative bronchiolitis and asthma triggered our initiating EV-D68-specific testing in standard of care RV/EV positive respiratory samples. We decided to examine the emergence of EV-D68 in as near real time as was feasible, particularly in light of the release of the CDC health advisory in early September via the Health Advisory Network (HAN) reporting an increased EV-D68 prevalence in hospitals and clinics nationwide [25]. We sought to identify differences in clinical presentations or illness progression that could aid in earlier clinical identification of EV-D68 patients and to describe use of medical resources during illness management of EV-D68 positive children compared to EV-D68 negative.