Abstract / Description
Lower respiratory infections (LRIs) are the foremost cause of infection-related mortality worldwide. However, the specific aetiological agents responsible for high hospitalisation rates and elevated coinfection risks across different populations have not been systematically investigated, primarily constrained by clinical practices that often target few pathogens and employ inconsistent testing methods across hospitals. Here, we collected 695,142 bronchoalveolar lavage fluid (BALF) samples from patients hospitalised with LRIs across 4758 hospitals of Chinese mainland between January 2022 and May 2025 and analysed 28 common respiratory pathogens using targeted next-generation sequencing (tNGS). Based on the real-world pathogen spectrum, we stratified the hospitalised patients undergoing BALF sampling into eight distinct age groups, corresponding to eight life-stages, and established life-stage-specific patterns of pathogen distribution. Subsequently, we identified 124 coinfecting pathogen pairs and three characteristic co-detection networks. 79.03% of observed co-detections occurred within these networks. Furthermore, our analysis revealed that bacteria and fungi such as KPN, PJ, and ABA were more frequently detected in hospitalised male patients, which indicates sex-specific differences in detection patterns. We also observed that males aged 0-4 years and 35+ years were more frequently represented among hospitalised patients with severe LRIs. These findings may inform age- and sex- stratified infectious disease prevention, control, and clinical management. Specifically, they may support public health practitioners in optimizing vaccination strategies; assist diagnostic developers in creating life-stage-specific diagnostic panels that prioritize commonly detected pathogens; and aid clinicians in assessing patterns of hospitalisation and co-detection based on nationwide data from BALF-sampled hospitalised LRI cases.