Abstract
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.
Highlights
The 2014 enterovirus D68 (EV-D68) strains clustered into a new sublineage within clade B. This is one of the largest pediatric cohorts described from the EV-D68 outbreak
[1] Since the circulation of EV-D68 has been limited to individual cases and small outbreaks as reported by the National Enterovirus Surveillance System (NESS). [2,3,4,5,6] In late summer of 2014, a large outbreak of EV-D68 associated with severe respiratory illness was identified in the Midwestern United States (US)
[7] Studies showed that the EV-D68 outbreak strains were associated with respiratory distress and disproportionately affected asthmatic children compared with rhinovirus/enterovirus (RV/EV-nonEV-D68) infections, which are the most common infectious triggers of asthma. [8,9,10,11,12,13,14] Those studies, 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]
Summary
Enterovirus D68 (EV-D68) was originally identified in 1962 in four children with severe respiratory tract infection in California. [1] Since the circulation of EV-D68 has been limited to individual cases and small outbreaks as reported by the National Enterovirus Surveillance System (NESS). [2,3,4,5,6] In late summer of 2014, a large outbreak of EV-D68 associated with severe respiratory illness was identified in the Midwestern United States (US). [7] Studies showed that the EV-D68 outbreak strains were associated with respiratory distress and disproportionately affected asthmatic children compared with rhinovirus/enterovirus (RV/EV-nonEV-D68) infections, which are the most common infectious triggers of asthma. [8,9,10,11,12,13,14] Those studies, 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]During the outbreak, the sequence variability of the EV-D68 strains from the US was compared with worldwide sequences, and it was shown that these EV-D68 strains mainly belonged to clade B. [15, 16] The characterization and circulation of EV-D68 strains within the same institution over time, and whether EV-D68 genomic loads are associated with enhanced clinical disease has not been described.The objectives of this study were to define the clinical and virologic impact of EV-D68 in a large cohort of children, including those with chronic medical conditions, hospitalized from May 2014 to November 2014 at our center. [8,9,10,11,12,13,14] Those studies, 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. [15, 16] The characterization and circulation of EV-D68 strains within the same institution over time, and whether EV-D68 genomic loads are associated with enhanced clinical disease has not been described. 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
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