Clinical severity of pediatric respiratory illness with enterovirus D68 compared with rhinovirus or other enterovirus genotypes

Mertz, Dominik; Alawfi, Abdulsalam; Pernica, Jeffrey M.; Rutherford, Candy; Luinstra, Kathy; Śmieja, Marek

doi:10.1503/cmaj.150619

Cited by 18 publications

(23 citation statements)

References 9 publications

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“…[13] In our study 68% of children with EV-D68 were admitted to the PICU, which is similar to the rates reported by Midgley et al [11], but significantly higher compared to the 20% reported by others. [10, 13, 14] Nevertheless, once admitted, PICU length of stay was comparable between children with EV-D68 vs. those in the RV/EV-non-EV-D68 group. The variance in PICU admissions between our study and others could be attributed to differences in clinical practices followed at different institutions.…”

Section: Discussionmentioning

confidence: 93%

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

et al. 2016

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BackgroundAn outbreak of enterovirus D68 (EV-D68) caused severe respiratory illness in 2014. The disease spectrum of EV-D68 infections in children with underlying medical conditions other than asthma, the role of EV-D68 loads on clinical illness, and the variation of EV-D68 strains within the same institution over time have not been described. We sought to define the association between EV-D68 loads and sequence variation, and the clinical characteristic in hospitalized children at our institution from 2011 to 2014.MethodsMay through November 2014, and August to September 2011 to 2013, a convenience sample of nasopharyngeal specimens from children with rhinovirus (RV)/EV respiratory infections were tested for EV-D68 by RT-PCR. Clinical data were compared between children with RV/EV-non-EV-D68 and EV-D68 infections, and among children with EV-D68 infections categorized as healthy, asthmatics, and chronic medical conditions. EV-D68 loads were analyzed in relation to disease severity parameters and sequence variability characterized over time.ResultsIn 2014, 44% (192/438) of samples tested positive for EV-D68 vs. 10% (13/130) in 2011–13 (p<0.0001). PICU admissions (p<0.0001) and non-invasive ventilation (p<0.0001) were more common in children with EV-D68 vs. RV/EV-non-EV-D68 infections. Asthmatic EV-D68+ children, required supplemental oxygen administration (p = 0.03) and PICU admissions (p <0.001) more frequently than healthy children or those with chronic medical conditions; however oxygen duration (p<0.0001), and both PICU and total hospital stay (p<0.01) were greater in children with underlying medical conditions, irrespective of viral burden. By phylogenetic analysis, the 2014 EV-D68 strains clustered into a new sublineage within clade B.ConclusionsThis is one of the largest pediatric cohorts described from the EV-D68 outbreak. Irrespective of viral loads, EV-D68 was associated with high morbidity in children with asthma and co-morbidities. While EV-D68 circulated before 2014, the outbreak isolates clustered differently than those from prior years.

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Section: Discussionmentioning

confidence: 93%

“…[8–14] Those studies, however, were mainly focused in otherwise healthy children and included limited data regarding the disease spectrum of EV-D68 in children with underlying medical conditions other than asthma. [10, 13, 14]…”

Section: Introductionmentioning

confidence: 99%

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

et al. 2016

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“…In this report, we describe a cohort of 511 patients with EV‐D68 and non‐EV‐D68 HRV/EV who presented to the ED and urgent care at Seattle Children's Hospital during the late summer and fall of 2014. This study provides a unique focus on patients who presented to the ED or urgent care and is the largest study to date of patients with EV‐D68 in this setting . Our large sample size enabled us to robustly demonstrate that pediatric patients in the ED or urgent care with EV‐D68 were hospitalized, had LRTI, and required respiratory support, albuterol, and steroids more often than their counterparts with non‐EV‐D68 HRV/EV.…”

Section: Discussionmentioning

confidence: 94%

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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“…Iwasaki et al reported low‐Ab responses against EV, such as echovirus, in children aged 2‐5 years presenting to hospitals with asthma exacerbations . Mertz et al also reported that EV68 is associated with asthma in children. These reports imply that EV may play a key role in allergic respiratory diseases such as asthma …”

Section: Introductionmentioning

confidence: 99%

Effect of enterovirus infections on asthma in young children: A national cohort study

Yeh

Lin

Hsu

2017

Eur J Clin Investigation

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Clinical severity of pediatric respiratory illness with enterovirus D68 compared with rhinovirus or other enterovirus genotypes

Cited by 18 publications

References 9 publications

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

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

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

Effect of enterovirus infections on asthma in young children: A national cohort study

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