Clinical Characteristics of Seasonal Human Coronavirus Infections Among Children in the Post-COVID-19 Pandemic Era: A Retrospective Study Comparing HCoV Species and SARS-CoV-2 in Hokkaido, Japan, From April 2021 to September 2025.
BACKGROUND Seasonal human coronaviruses (HCoVs) can cause acute respiratory infections in children; however, their epidemiology and clinical features in the post-coronavirus disease 2019 era remain incompletely characterized. METHODS We retrospectively analyzed children under 16 years old with respiratory symptoms who underwent multiplex polymerase chain reaction testing at a hospital in Hokkaido, Japan, between April 2021 and September 2025. Demographic and clinical data were extracted from medical records. RESULTS Among 15,197 specimens, 1212 (8.0%) tested positive for HCoVs, including 361 (29.8%) single infections. OC43 was the most frequently detected species (530/1212; 43.7%), followed by NL63 (382/1212; 31.5%), HKU1 (277/1212; 22.9%) and 229E (56/1212; 4.6%). HCoVs circulated year-round, with seasonal peaks shifting from autumn to winter in 2021 and summer in 2022 to winter-spring from 2023 onward. Among single HCoV infections, the median age was 2.0 (interquartile range, 1.0-4.0) years, and 64.8% were male children. Upper respiratory infection was the most common diagnosis, and 14.7% of patients required hospitalization. Species-specific differences were observed: OC43 was associated with younger age, NL63 with croup and HKU1 with headache. Compared with severe acute respiratory syndrome coronavirus 2, seasonal HCoV infections occurred at younger ages and were more frequently associated with lower respiratory tract involvement, despite similar hospitalization rates. CONCLUSIONS Seasonal patterns of HCoVs were temporarily altered during the coronavirus disease 2019 pandemic but returned to their pre-pandemic winter-spring predominance from 2023. Species-specific clinical differences were observed; compared with severe acute respiratory syndrome coronavirus 2, HCoV infections occurred at younger ages and were more often associated with lower respiratory tract involvement.