Post-Pandemic Shifts in Pediatric Respiratory Pathogens and Co-Infection Dynamics in Northwest China: A Large-Scale Retrospective Study from 2021 to 2025

Background and objective The COVID-19 pandemic and subsequent changes in public health policies have profoundly altered respiratory pathogen circulation patterns. This study aimed to characterize pathogen distribution, temporal trends, and co-infection dynamics among pediatric patients with respiratory tract infection (RTI) across epidemic and post-epidemic periods in northwest China. Methods We retrospectively analyzed 37,678 hospitalized pediatric RTI cases at Xi’an Children’s Hospital from July 2021 to April 2025. Multiplex reverse transcription PCR with capillary electrophoresis was used to detect 13 common respiratory pathogens. We compared pathogen prevalence and co-infection rates between the epidemic (2021-2022) and post-epidemic (2023-2025) periods. Multivariate logistic regression and co-infection network visualization were used to identify risk factors and interaction patterns. Results Among all cases, 60.6% tested positive for at least one pathogen, with human rhinovirus (HRV, 11.60%), Mycoplasma pneumoniae (Mp, 9.78%), and human respiratory syncytial virus (HRSV, 8.66%) most frequently detected. Post-epidemic periods saw significant increases in Mp, HRSV, and co-infections (from 4.05% to 11.55%, p < 0.001). The predominant co-infection was HRV-Mp. Co-infection risk was significantly higher in children aged 0-12 years and during the post-epidemic period. Co-infection peaks occurred consistently in late autumn. Conclusion This large-scale study reveals a substantial post-pandemic resurgence of Mp, HRSV, and co-infection among children in northwest China. HRV played a central role in co-infection networks. The findings highlight the importance of enhancing surveillance, optimizing antimicrobial use, and developing preparedness frameworks with specific attention to pediatric co-infection dynamics.