Retrospective Study of the Upsurge of Enterovirus D68 Clade D1 among Adults (2014-2018)

Abstract

Enterovirus D68 (EV-D68) has emerged as an agent of epidemic respiratory illness and acute flaccid myelitis in the paediatric population but data are lacking in adult patients. We performed a 4.5-year single-centre retrospective study of all patients who tested positive for EV-D68 and analysed full-length EV-D68 genomes of the predominant clades B3 and D1. Between 1 June 2014, and 31 December 2018, 73 of the 11,365 patients investigated for respiratory pathogens tested positive for EV-D68, of whom 20 (27%) were adults (median age 53.7 years [IQR 34.0-65.7]) and 53 (73%) were children (median age 1.9 years [IQR 0.2-4.0]). The proportion of adults increased from 12% in 2014 to 48% in 2018 (p = 0.01). All adults had an underlying comorbidity factor, including chronic lung disease in 12 (60%), diabetes mellitus in six (30%), and chronic heart disease in five (25%). Clade D1 infected a higher proportion of adults than clades B3 and B2 (p = 0.001). Clade D1 was more divergent than clade B3: 5 of 19 amino acid changes in the capsid proteins were located in putative antigenic sites. Adult patients with underlying conditions are more likely to present with severe complications associated with EV-D68, notably the emergent clade D1.

Keywords: adult patients; enterovirus D68; molecular epidemiology; next-generation sequencing; paediatric patients; respiratory conditions.

Figure 1

Monthly distribution of EV-D68 infections, Clermont-Ferrand, 2014–2018. Histogram colours match the EV-D68 clade related to the infection case as indicated on the graph. Hatched colours match EV-D68 in adult patients. Solid colours match EV-D68 in paediatric patients. UT: untyped.

Figure 2

Phylogeny of EV-D68 clade D and molecular variation of viral proteins. (A) The phylogenetic tree was obtained with the Nextstrain pipeline using a global dataset of 734 EV-D68 whole genomes available in Genbank (as of 1 February 2020) and 30 new sequences obtained in this study. The solid red diamonds indicate statistical support of main nodes (posterior probability ≥0.98). The colours of sequence names match with age groups of related patients: red and blue colours match with adults (>16 years) and children (≤16 years), respectively. Sequence names in black had no corresponding information on related patient age. The branches are coloured according to the geographic origin. (B) Identification of protein positions having amino acid residues specific to clade D. The amino acid positions from other EV-D68 clades are expressed in percentages on the graph with Weblogo 3 [14]. Amino acids with pink background indicate specific positions. Amino acids with blue background match unspecific positions. Amino acids are coloured according to their chemistry.

Figure 3

Phylogeny of EV-D68 clade B3 and molecular variation of viral proteins. (A) The phylogenetic tree was obtained with the Nextstrain pipeline using a global dataset of 734 EV-D68 whole genomes available in Genbank (as of 1 February 2020) and 30 new sequences obtained in this study. The solid red diamonds indicate statistical support of main nodes (posterior probability ≥0.98). The colours of sequence names match with age groups of related patients: red and blue colours match with adults (>16 years) and children (≤16 years), respectively. Sequence names in black had no corresponding information on related patient age. The branches are coloured according to the geographic origin. (B) Identification of protein positions having amino acid residues specific to clade B3. The amino acid positions from other EV-D68 clades are expressed in percentages on the graph with Weblogo 3 [14]. Amino acids with pink background indicate specific positions. Amino acids with blue background match unspecific positions. Amino acids are coloured according to their chemistry.