Lower Respiratory Tract Co-infection of Streptococcus pneumoniae and Respiratory Syncytial Virus Shapes Microbial Landscape and Clinical Outcomes in Children

XiaoRan YU¹Xuemei Yang²Yiqin Song³Jie Yu²婷婷 蒋³He Tang³Xiaoxuan Yang³Xi Zeng²Jing Bi³A-dong Shen²Lin Sun^2*

• ¹Peking University, Beijing, China
• ²Beijing Children’s Hospital, Capital Medical University, Beijing, Beijing Municipality, China
• ³Baoding Hospital, Beijing Children’s Hospital, Capital Medical University, Baoding, Hebei Province, China

Lower respiratory tract infections (LRTI), which are most commonly caused by Streptococcus pneumoniae (SP) and respiratory syncytial virus (RSV), pose a substantial global health burden in children. However, the causal pathways of bacterial-viral co-infections, particularly the mechanisms by which commensal microbiota could modulate SP-RSV-associated LRTI outcomes remain to be elucidated. A population-based cross-sectional study was conducted on children aged 0-18 years who were admitted to Beijing Children's Hospital and Baoding Children's Hospital in China from September 2021 to August 2022. Children with LRTI who underwent respiratory pathogen testing were divided into SP single infection and SP-RSV co-infection groups, with sex- and time-matched non-LRTI children as controls. Sputum and LRT secretion samples were collected for microbiota analysis using 16S rRNA sequencing, and child characteristics were obtained from medical records and pharmacy data. A total of 125 children with LRTI (84 with SP infection and 41 with SP-RSV co-infection) and 85 children without LRTI were recruited for this study. We found that LRT microbiota composition was strongly related to age, with a more pronounced increase in Shannon index within the first 5 years of life. Children with SP and RSV infection exhibited significantly altered microbiota composition in comparison to children without LRTI, particularly a higher abundance of Streptococcus. The competitive interactions among respiratory bacteria were found to be more complex in the SP single-infection group and simpler in the SP-RSV co-infection group. Our findings show that RSV co-infection exacerbates SP-induced LRTI microbiota disorder and disease severity. This study may help us to better understand the characteristics of SP-RSV interaction and provide direction for the pathogen diagnosis of LRTI.