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Background During COVID-19-related public health non-pharmaceutical prevention measures, such as social distancing, lockdown periods and use of face masks, a decrease in viral respiratory and gastroenterological infections was observed worldwide. Following discontinuation of preventative measures, a potential increase of respective infections outside of their usual seasons was a matter of concern. Method We aimed to illustrate annual distribution of confirmed viral infections between 2017 and 2021 based on 32,506 clinical samples in a German pediatric tertiary care center and to explore the impact of the COVID-19 pandemic on the epidemiology of these infections in children. Results While a decrease in overall viral infections was observed during the first and second lockdown period, an extraordinary increase in the number of viral respiratory infections, predominantly caused by human Rhino-/Enterovirus and respiratory syncytial virus (RSV), was observed after relaxation of preventive measures. Notably, Rhino-/Enterovirus infections increased 4-fold (2020 vs. 2019) and 16-fold (2021 vs. 2019). The occurrence of RSV was observed beginning from June to August 2021 and reached an all-time record with a 25- to 50-fold increase in numbers in September and October 2021 in relation to previous pre-pandemic years (2017–2019). In contrast, for non-respiratory viruses (i.e. Rota-/Norovirus), the effect on respective seasonal patterns was only minimal compared to previous years. Conclusion The observed increase in respiratory infections in children is worrying and is already causing hospitals to become overburdened. Enhanced vigilance will be key to face clinical challenges due to these epidemiological changes in viral disease patterns in the months to come.

The rising of old foes: impact of lockdown periods on “non-SARS-CoV-2” viral respiratory and gastrointestinal infections