ICU-acquired infections and mortality in community-acquired pneumonia–induced sepsis: Insights from a transcriptomic analysis

Objectives To evaluate the association between ICU-acquired infections and 28-day mortality in pneumonia-induced sepsis and to explore associated immune-related gene expression patterns. Methods A secondary analysis was performed using the publicly available GSE65682 dataset, including adult ICU patients with sepsis secondary to community-acquired pneumonia (CAP) or hospital-acquired pneumonia (HAP). Patients were stratified based on the development of ICU-acquired infections. 28-day mortality and whole-blood leukocyte gene expression at ICU admission were compared between groups. Results Among 144 patients, 20 developed ICU-acquired infections. In the CAP subgroup, ICU-acquired infections were associated with numerically higher 28-day mortality compared to those without infection (45.5% vs. 18.2%, p = 0.05), although this finding should be interpreted with caution given the retrospective study design and limited sample size. In HAP patients, a similar pattern was not observed (22.2% vs. 19.6%). Transcriptomic analysis showed significant downregulation of the interleukin-7 receptor (IL7R) in CAP patients who developed ICU-acquired infections, with PRKACB and CD3D also demonstrating a downward trend. Conclusion These findings suggest that early immune dysregulation may be associated with an increased susceptibility to secondary infections and potentially worse outcomes among CAP patients. IL7R may represent a candidate signal of immune dysregulation and warrants further investigation and validation in future studies.