Seasonal shifts in respiratory pathogen co-infections and the associated differential induction of cytokines in children.

In the post-pandemic era, research on respiratory diseases should refocus on pathogens other than the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Respiratory pathogens, highly infectious to children, with to different modes of infection, such as single-pathogen infections and co-infections. Understanding the seasonal patterns of these pathogens, alongside identifying single infections and co-infections and their impact on the pediatric immune status, is crucial for clinical diagnosis, treatment, and prognosis in children. Our study found that from December 2023 to April 2024, the main co-infection combinations in children shifted from Mycoplasma pneumonia and influenza virus A (MP + IVA) to Bordetella pertussis and rhinovirus (BP + RhV). To explore the impact of these infections, two cohorts were established to analyze the effects of single and co-infections of four respiratory pathogens, MP, IVA, BP, and RhV, on the immune status of pediatric patients. Using multi-cytokine analysis, cytokines, such as PDGF-BB, that were differentially expressed between patients with single and co-infections were identified. Additionally, we observed that children with single-pathogen infections generally exhibited more severe conditions, as evidenced by higher overall cytokine expression than those with co-infections. Our findings provide an important theoretical basis for understanding the pathogenic mechanisms of single and co-infections of respiratory pathogens and clinically differentiating pediatric patients with various respiratory infections.