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Several respiratory pathogens are responsible for influenza-like illness (ILI) and severe respiratory infections (SARI), among which human respiratory syncytial virus (hRSV) represents one of the most common aetiologies. We analysed the hRSV prevalence among subjects with ILI or SARI during the five influenza seasons before the emergence of SARS-CoV-2 epidemic in Sicily (Italy). Respiratory specimens from ILI outpatients and SARI inpatients were collected in the framework of the Italian Network for the Influenza Surveillance and molecularly tested for hRSV-A and hRSV-B. Overall, 8.1% of patients resulted positive for hRSV. Prevalence peaked in the age-groups <5 years old (range: 17.6–19.1%) and ≥50 years old (range: 4.8–5.1%). While the two subgroups co-circulated throughout the study period, hRSV-B was slightly predominant over hRSV-A, except for the season 2019–2020 when hRSV-A strongly prevailed (82.9%). In the community setting, the distribution of hRSV subgroups was balanced (47.8% vs. 49.7% for hRSV-A and hRSV-B, respectively), while most infections identified in the hospital setting were caused by hRSV-B (69.5%); also, this latter one was more represented among hRSV cases with underlying diseases, as well as among those who developed a respiratory complication. The molecular surveillance of hRSV infections may provide a valuable insight into the epidemiological features of ILI/SARI. Our findings add new evidence to the existing knowledge on viral aetiology of ILI and SARI in support of public health strategies and may help to define high-risk categories that could benefit from currently available and future vaccines.

Respiratory Syncytial Virus: New Challenges for Molecular Epidemiology Surveillance and Vaccination Strategy in Patients with ILI/SARI