Inflammatory Mediation of the Association Between Latent Clinical Phenotypes and Multidimensional Outcomes in Pediatric Community-Acquired Pneumonia.

INTRODUCTION: To analyse the association between latent clinical phenotypes and multidimensional outcomes in pediatric community-acquired pneumonia and evaluate the role of inflammation in this relationship. METHODS: This retrospective observational cohort study included 700 hospitalized children with community-acquired pneumonia at Shanghai Sixth People's Hospital from January 1, 2023 to June 30, 2025. Latent class analysis was performed to identify clinical phenotypes. We assessed the association between community-acquired pneumonia subgroups and multidimensional outcomes. Joint effects of community-acquired pneumonia subgroups and c-reactive protein/interleukin-6 on multidimensional outcomes were investigated. Associations between individual respiratory pathogens and multidimensional outcomes were also assessed. Mediation analyses were conducted to examine the role of c-reactive protein/interleukin-6 in the association between clinical phenotypes/pathogens and multidimensional outcomes. RESULTS: Older-full term-Mycoplasma pneumoniae infection subgroup showed higher risk of severe pneumonia and kidney injury, longer disease duration, lower risk of cardiac injury, lower serum aspartate aminotransferase, and higher urine protein level. C-reactive protein mediated 4.6%, 10.3%, and 6.9% of the effect of older-full term-Mycoplasma pneumoniae infection subgroup on the risk of severe pneumonia, cardiac injury, and kidney injury, respectively. Interleukin-6 mediated 6.1% and 12.5% of the effect of older-full term-Mycoplasma pneumoniae infection subgroup on the risk of severe pneumonia, and kidney injury, respectively. Older-full term-Mycoplasma pneumoniae infection subgroup with higher c-reactive protein/interleukin-6 showed higher risk of severe pneumonia and kidney injury and lower risk of cardiac injury. Mycoplasma pneumoniae infection was associated with higher risk of severe pneumonia, kidney injury, and longer disease duration. Adenovirus infection was associated with higher risk of kidney injury. Interleukin-6 mediated 5.9% and 11.6% of the effect of Mycoplasma pneumoniae infection on the risk of severe pneumonia and kidney injury, respectively. C-reactive protein mediated 17.5% of the effect of adenovirus infection on the risk of kidney injury. CONCLUSION: The older-full term-Mycoplasma pneumoniae infection subgroup showed an unfavorable outcome profile, whereas the younger-preterm-virus infection subgroup was associated with higher cardiac injury risk. Mycoplasma pneumoniae and adenovirus were associated with specific poor outcomes in pediatric community-acquired pneumonia. Inflammation partially mediated the associations between phenotypes, pathogens, and outcomes, supporting phenotype-based risk assessment.