Enterovirus (EV)-D68 in Pediatric Patients with Respiratory Tract Infection: the Circulation of new B3 Clade in Italy

BACKGROUND: EV-D68 is an emerging infectious agent that has been found associated with both mild and severe respiratory diseases and neurological clinical manifestations. Four clades with a number of subclades that can circulate or co-circulate during different periods have been identified. However, molecular evolution of EV-D68 is not known as it is the possible association between specific genetic variants and the development of severe cases. To solve these problems, genetics of strains identified during an outbreak of EV-D68 infection that occurred in Italy during the period March-October 2016 were studied. METHODS: Nasopharyngeal samples obtained from children admitted to the Emergency Room for respiratory infection were tested with a previously validated specific real-time PCR for detection and quantification of EV-D68. Phylogenetic analysis (PhA) of the virus was performed sequencing the major capsid protein (VP1). Moreover, tests for detection of selective pressure were carried out. RESULTS: Respiratory samples of 390 children were tested. Twenty-two patients (5.6%; median age, 47 months) were infected by EV-D68. All but three had a lower respiratory tract infection but none of these was severe, although in a few cases a transient reduction of SaO2 level was evidenced at admission. All the strains belonged to the EV-D68 subclade B3. No evidence of increased clinical severity associated with specific molecular signatures of VP1 sequence or viral load was shown. B3 strains had 92.3% and 94.7% nucleotide identity with B3 clades identified in other countries where a number of very severe cases was diagnosed. No sign of selective pressure was found. CONCLUSION: EV-D68 subclade B3 was the only cause of the EV-D68 diseases diagnosed in Italy during 2016.The same subclade was found in Northern Europe, China and the USA in the same period. This suggests that all the outbreaks had a common origin and EV-D68 B3 has become the preeminent EV-D68 strain causing disease worldwide. No specific characteristic of EV-D68 VP1 has been found associated with disease characteristics, in contrast with what has been evidenced with other studies. Further studies on full-genome sequencing in larger cohorts of patients are needed. DISCLOSURES: All authors: No reported disclosures.