Unexpected Pediatric Cluster of Enterovirus C105, Verona, Italy

Abstract

In an epidemiologic investigation of Enterovirus (EV) infections in a Verona hospital, September 2022-September 2024, we detected EV-C105 in six pediatric patients with upper respiratory symptoms between March and May 2023. The primary objective was to describe the local incidence of EV cases. The secondary objective was to perform Sanger's genomic characterization and the whole-genome sequencing (WGS) of EV-C105. The proportion of positive EV results was calculated based on routine molecular method testing. An available cohort of 114 underwent Sanger sequencing, and the six EV-C105 were characterized with WGS. Overall, 96% EV results were from the upper respiratory tract. The total proportion of positives in children was 83%. Out of the typed 114, 90% were Rhinoviruses and 9%, EVs. Notably, six pediatric cases were EV-C105, placing together in a unique cluster with 99% of nucleotides belonging to the European lineage with the highest Average Nucleotide Identity, including EV-C104, EV-C109, and EV-C118. Our data describes the first cluster indicating that EV-C105 incidence may be higher than previously estimated. However, a limitation for affirming this hypothesis is the lack of a more in-depth epidemiological investigation on a larger case series with the possibility of including data from coordinated laboratories.

Keywords: RNA; Sanger sequencing; enterovirus; enterovirus-C105; rhinovirus; whole-genome sequencing.

Figure 1

Weekly distribution of the 208 cumulative positive EV/RV cases in 2022 and 2024. EV-C105s are identified in orange.

Figure 2

Phylogenetic trees based on partial VP1 (A) and whole-genome nucleotide sequences (B) with all available Enterovirus C105 genome sequences. The heatmap indicates the sampling date (2007–2023), while each node is colored according to the origin continent (Europe, Northern America, Southern America, Africa, Asia). The robustness of the branches is shown on the label nodes with bootstrap values (bootstrap support cutoff, ≥70%). The units of branch length are the number of substitutions divided by the length of the sequence. Enterovirus C109 sequences were used as outgroups.