Ecological reshaping of pediatric respiratory pathogen profiles after COVID-19-related non-pharmaceutical interventions were lifted: a 5-year interrupted time-series study

Background COVID-19-related non-pharmaceutical interventions (NPIs) disrupted the circulation of many respiratory pathogens. After these measures were lifted, pediatric respiratory pathogen activity may have changed in pathogen-specific ways. However, laboratory-based evidence using continuous multi-year data, interrupted time-series analysis, and contextual factors such as meteorology, air quality, and school calendars remains limited. Methods We conducted a single-center retrospective laboratory study of pediatric and neonatal inpatients aged 0–14 years with clinically diagnosed lower respiratory tract infection from January 2021 to December 2025. After 7-day deduplication within the same child, 20,250 throat-swab testing records were included. The NPI period was January 2021–December 2022, and the post-NPI period was January 2023–December 2025. Thirteen pathogen categories were analyzed using period comparisons, interrupted time-series models, and multivariable logistic regression incorporating meteorological factors, air quality index, and school-term status. Results Overall positivity was higher in the post-NPI period than in the NPI period (75.4% vs. 58.8%), and co-detection was also higher in the post-NPI period (15.2% vs. 6.0%). Pathogen-specific interrupted time-series analysis showed heterogeneous patterns: human adenovirus showed a robust immediate level decrease (−13.00 percentage points; 95% CI, −20.13 to −5.87; FDR-adjusted P = 0.005), whereas human rhinovirus showed a significant positive trend change after the January 2023 interruption (+1.07 percentage points per month; 95% CI, 0.63–1.50; FDR-adjusted P < 0.001), with a positive post-NPI slope (+0.64 percentage points per month). Higher temperature was associated with lower positivity of human respiratory syncytial virus, influenza A H1N1 (2009) virus, and influenza B virus, but higher positivity of human parainfluenza virus and human bocavirus. School-term status was associated with higher human rhinovirus positivity (aOR, 1.84; 95% CI, 1.34–2.52; FDR-adjusted P = 0.002). Conclusion The NPI and post-NPI periods showed distinct and heterogeneous temporal patterns in pediatric respiratory pathogen detection. These findings support integrated hospital-based laboratory surveillance centered on pathogen-specific temporal trends and interpreted alongside demographic, multi-pathogen, environmental, school-calendar, and longer-term temporal context.