BackgroundCo-infection with other pathogens can alter the severity and clinical outcomes of viral infections. However, the information regarding viral co-infections in pediatric coronavirus disease 2019 (COVID-19) cases is still limited. MethodsThis is a nationwide, retrospective cohort study using the data from the COVID-19 Registry Japan. The pediatric (<18 years), laboratory confirmed, hospitalized COVID-19 patients in the Omicron variant of concern predominant period (January 2022 to January 2024) were included. Co-infection was investigated by multiplex PCR. We compared clinical characteristics, symptoms, severity, and outcomes between children with and without co-infection. ResultsAmong 245 hospitalized pediatric COVID-19 patients, 78 (31.8%) had co-infections. The patient backgrounds of the “co-infection” and “SARS-CoV-2 alone” groups were similar, although age distribution was different, with a lower number of patients over 12 years in the co-infection group (n=2, 2.6% vs. n=29, 17.4%; P<0.001). Among the patients with co-infection, the most common pathogen was enterovirus/rhinovirus (51.3%), followed by parainfluenza virus (23.1%) and adenovirus (12.8%). Patients with co-infection more commonly had respiratory symptoms, including SpO2 < 96%, shortness of breath, runny nose, and wheezing. Requirement of non-invasive oxygen support was higher in the co-infection group (n=27, 34.6% vs. n=28, 16.8%, P=0.006). By multivariable logistic regression analysis, co-infection and presence of any comorbidity were identified as significant risk factors for necessity of oxygen therapy (odds ratio [95% confidence interval] 2.44 [1.29-4.63] and 3.99 [2.07-7.82], respectively). ConclusionsViral co-infection may increase the risk of respiratory distress in pediatric COVID-19 patients.