Introduction: Respiratory syncytial virus represents one of the most important respiratory pathogens affecting all age groups. Following the extensive non-pharmaceutical interventions (NPIs) and societal behavioral changes of 2020 and 2021 in wake of the SARS-CoV-2 pandemic, a marked epidemiological shift was observed in 2022 and 2023.

Methods: The aim of this study was to characterize the local molecular epidemiology of RSV infections in the seasons of 2021/2022 and 2022/2023 to the three pre-pandemic seasons by sequence analysis of the complete G and F genes. Additionally, clinical data were retrieved from patient charts to determine the clinical significance of RSV infections of the same period.

Findings: In season 2021/2022 the peak of RSV detections occurred in calendar week 40 of 2021, 18 weeks before the usual peak observed in the three pre-pandemic seasons. In season 2022/2023, the peak was detected in week 1 of 2023. The sequence analysis of RSV-A and RSV-B strains revealed a close phylogenetic relatedness with assignment to the same genotype regardless of the season of origin in the G gene. The analysis of the F gene revealed a close relatedness as well, however, an amino acid drift in the antigenic regions was observed especially for RSV-B. Although the positivity rates were comparable, the cases numbers for seasons 2021/2022 and 2022/2023 were markedly different. While in season 2022/2023 as many cases as in all pre-pandemic seasons were detected, season 2021/2022 showed the lowest case number and a significantly higher amount of patients under the age of 60 (<0.001). Most of the assessed clinical parameters were similar in comparison to the three pre-pandemic seasons. High rates of comorbidities, lower respiratory tract infections, and ICU admissions prevailed in the studied adult population.

Conclusion: The NPIs in wake of the SARS-CoV-2 pandemic had a tremendous impact on the epidemiologic characteristics and seasonality of RSV. The continued effect of behavioral changes on the circulation of respiratory viruses as well as the potential implementations of new treatment strategies warrant further epidemiologic studies of this common pathogen.