Enterovirus D68 in Hospitalized Children: Sequence Variation, Viral Loads and Clinical Outcomes

Moyer, Katherine; Wang, Huanyu; Salamon, Douglas; Leber, Amy; Mejías, Asunción

doi:10.1371/journal.pone.0167111

Cited by 21 publications

(28 citation statements)

References 24 publications

(36 reference statements)

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“…Preexisting asthma was significantly associated with medically attended EV-D68 infection, confirming observations from other studies [4, 9, 26, 27]. The prospective study design with systematic testing for EV-D68 is a strength of our study and reduced the potential for selection bias compared with case series or retrospective studies in which testing was performed on the basis of clinician discretion.…”

Section: Discussionsupporting

confidence: 85%

“…Although children with asthma were more likely to have medically attended EV-D68 infection and were more often admitted from the ED, hospital outcomes were similar between children with and without preexisting asthma. Some reports have shown a more severe clinical course among hospitalized children with EV-D68 infection who have preexisting asthma [4, 9], whereas others have not observed this difference [8]. It is possible that differences in study design or power could explain differences in findings.…”

Section: Discussionmentioning

confidence: 99%

“…During the 2014 outbreak, a history of asthma or reactive airway disease was common among children with medically attended EV-D68 infection [8] and in some studies was associated with more severe illness [4, 9]. …”

mentioning

confidence: 99%

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Enterovirus D68 Infection Among Children With Medically Attended Acute Respiratory Illness, Cincinnati, Ohio, July–October 2014

Biggs

McNeal

Nix

et al. 2017

Clinical Infectious Diseases

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Background Enterovirus D68 (EV-D68) caused a widespread outbreak of respiratory illness in the United States in 2014, predominantly affecting children. We describe EV-D68 rates, spectrum of illness, and risk factors from prospective, population-based acute respiratory illness (ARI) surveillance at a large US pediatric hospital. Methods Children <13 years of age with ARI and residence in Hamilton County, Ohio were enrolled from the inpatient and emergency department (ED) settings at a children’s hospital in Cincinnati, Ohio, from 1 July to 31 October 2014. For each participant, we interviewed parents, reviewed medical records, and tested nasal and throat swabs for EV-D68 using real-time reverse-transcription polymerase chain reaction assay. Results EV-D68 infection was detected in 51 of 207 (25%) inpatients and 58 of 505 (11%) ED patients. Rates of EV-D68 hospitalization and ED visit were 1.3 (95% confidence interval [CI], 1.0–1.6) and 8.4 per 1000 children <13 years of age, respectively. Preexisting asthma was associated with EV-D68 infection (adjusted odds ratio, 3.2; 95% CI, 2.0–5.1). Compared with other ARI, children with EV-D68 were more likely to be admitted from the ED (P ≤ .001), receive supplemental oxygen (P = .001), and require intensive care unit admission (P = .04); however, mechanical ventilation was uncommon (2/51 inpatients; P = .64), and no deaths occurred. Conclusions During the 2014 EV-D68 epidemic, high rates of pediatric hospitalizations and ED visits were observed. Children with asthma were at increased risk for medically attended EV-D68 illness. Preparedness planning for a high-activity EV-D68 season in the United States should take into account increased healthcare utilization, particularly among children with asthma, during the late summer and early fall.

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Section: Discussionsupporting

confidence: 85%

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Enterovirus D68 Infection Among Children With Medically Attended Acute Respiratory Illness, Cincinnati, Ohio, July–October 2014

Biggs

McNeal

Nix

et al. 2017

Clinical Infectious Diseases

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“…Testing was mostly PCR based; either a laboratory developed real-time PCR or a multiplex PCR panel (FilmArray Respiratory Panel; BioFire, Salt Lake City, UT). (17) EHR were reviewed for demographic and clinical data including presence of comorbidities, which were categorized in: prematurity, congenital heart disease, chronic lung disease, immunodeficiency, neuromuscular disorders and genetic syndromes. (18–21) Information regarding length of stay, need and duration of PICU stay, mechanical ventilation, and hospital readmissions was also collected.…”

Section: Methodsmentioning

confidence: 99%

Discharge Criteria for Bronchiolitis

Garcia-Maurino

Moore‐Clingenpeel

Wallihan

et al. 2018

Pediatric Infectious Disease Journal

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Background: Admission criteria and standardized management strategies for bronchiolitis are addressed in several guidelines and have shown to be beneficial; however, guidance regarding discharge criteria is limited and widely variable. We assessed the impact on clinical outcomes of a discharge protocol for children <2 years of age hospitalized with bronchiolitis in a tertiary care pediatric hospital. Methods: In October 2013, a protocol to standardize the discharge of children with bronchiolitis was implemented in the infectious diseases (ID) ward but not in other pediatric units caring for these children (non-ID). The protocol included objective clinical criteria and a standardized oxygen weaning pathway. Patients were identified via International Classification of Diseases-9 codes and data manually reviewed. We compared length of stay (LOS) and readmission rates within 2 weeks of discharge according to protocol implementation (ID versus non-ID), adjusted for demographic factors, comorbidities, viral etiology and stratified by pediatric intensive care unit admission. Results: From October 2013 to May 2015, 1118 children were hospitalized in ID and 695 in non-ID units. Median age was 4.5 months, 55% were males and 28% had comorbidities. LOS was 36% longer in non-ID units (risk ratio: 1.36 [1.27–1.45]; P < 0.001) adjusted for age, gender, comorbidities and viral etiology. Difference in LOS remained significant after excluding children with comorbidities and stratifying by pediatric intensive care unit admission. Readmission rates were comparable between units (ID, 2.9% versus non-ID, 2.6%). Conclusions: A standardized discharge protocol for bronchiolitis reduced LOS without increasing readmission rates. Unifying bronchiolitis discharge criteria and oxygen weaning pathways could positively impact hospital-based patient care for this condition.

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“…Factors associated with inpatient admission in these patients are not well described, and the role of viral load in disease severity has not been investigated systematically. Pediatric patients with asthma are of particular interest as asthma affects nearly 10% of children, and data regarding EV‐D68 disease severity within this group have been conflicting . Our study aims to define the burden of EV‐D68 in a large cohort of pediatric patients presenting for urgent or emergent care in the ED or urgent care clinic at a regional children's hospital and to compare the clinical presentation, role of comorbidities, and outcomes between patients with EV‐D68 and those with other strains of human rhinovirus/enterovirus (HRV/EV) during an outbreak.…”

Section: Introductionmentioning

confidence: 99%

Enterovirus D‐68 in children presenting for acute care in the hospital setting

Savage

Kuypers

Chu

et al. 2018

Influenza Resp Viruses

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BackgroundSevere respiratory disease associated with enterovirus D68 (EV‐D68) has been reported in hospitalized pediatric patients. Virologic and clinical characteristics of EV‐D68 infections exclusively in patients presenting to a hospital Emergency Department (ED) or urgent care have not been well defined.MethodsMid‐nasal swabs from pediatric patients with respiratory symptoms presenting to the ED or urgent care were evaluated using a commercial multiplex PCR platform. Specimens positive for rhinovirus/enterovirus (HRV/EV) were subsequently tested using real‐time reverse‐transcriptase PCR for EV‐D68. The PCR cycle threshold (CT) was used as a viral load proxy. Clinical outcomes were compared between patients with EV‐D68 and patients without EV‐D68 who tested positive for HRV/EV.ResultsFrom August to December 2014, 511 swabs from patients with HRV/EV were available. EV‐D68 was detected in 170 (33%) HRV/EV‐positive samples. In multivariable models adjusted for age and underlying asthma, patients with EV‐D68 were more likely to require hospitalization for respiratory reasons (odds ratio (OR): 3.11, CI: 1.85‐5.25), require respiratory support (OR: 1.69, CI: 1.09‐2.62), have confirmed/probable lower respiratory tract infection (LRTI; OR: 3.78, CI: 2.03‐7.04), and require continuous albuterol or steroids (OR: 3.91, CI: 2.22‐6.88 and OR: 4.73, CI: 2.65‐8.46, respectively). Higher EV‐D68 viral load was associated with need for respiratory support and LRTI in multivariate models.ConclusionsAmong pediatric patients presenting to the ED or urgent care, EV‐D68 causes more severe disease than non‐EV‐D68 HRV/EV independent of underlying asthma. High viral load was associated with worse clinical outcomes. Rapid and quantitative viral testing may help identify and risk stratify patients.

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Enterovirus D68 in Hospitalized Children: Sequence Variation, Viral Loads and Clinical Outcomes

Cited by 21 publications

References 24 publications

Enterovirus D68 Infection Among Children With Medically Attended Acute Respiratory Illness, Cincinnati, Ohio, July–October 2014

Enterovirus D68 Infection Among Children With Medically Attended Acute Respiratory Illness, Cincinnati, Ohio, July–October 2014

Discharge Criteria for Bronchiolitis

Enterovirus D‐68 in children presenting for acute care in the hospital setting

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