Abstract Rationale Sepsis due to pneumonia remains a leading cause of intensive care unit (ICU) admissions and mortality. The development of ICU-acquired infections may further worsen outcomes. This study aimed to evaluate the impact of ICU-acquired infections on 30-day mortality in pneumonia-induced sepsis and to explore associated immune-related gene expression profiles. Methods A secondary analysis was conducted using the publicly available Gene Expression Omnibus dataset GSE65682. Adult ICU patients with sepsis secondary to community-acquired pneumonia (CAP) or hospital-acquired pneumonia (HAP) were included. Patients were stratified based on the development of ICU-acquired infections. Thirty-day mortality and whole-blood leukocyte gene expression at ICU admission were compared between groups using SPSS version 30, with visualizations created in GraphPad Prism version 10. Results Among 144 patients with pneumonia-induced sepsis, 20 developed ICU-acquired infections. In the CAP subgroup, ICU-acquired infections were associated with a significantly higher 30-day mortality rate compared to those without infections (45.5% vs. 18.2%, p = 0.05). This difference was not observed in HAP patients (22.2% vs. 19.6%, p = 0.94). Transcriptomic analysis revealed significant downregulation of interleukin-7 receptor (IL7R) (p = 0.01) in cases with ICU-acquired infections within the CAP subgroup. Protein kinase cAMP-activated catalytic subunit beta (PRKACB) and CD3 delta subunit of T-cell receptor complex (CD3D) also showed a downward trend. Conclusion ICU-acquired infections are associated with increased mortality in CAP-induced sepsis and are linked to early downregulation of key immune-related genes. These findings suggest that immune dysfunction may predispose patients to secondary infections and worse outcomes. Gene expression markers such as IL7R may help identify high-risk patients and guide targeted immune-based interventions. This abstract is funded by: Scientific Research Deanship at University of Ha’il – Saudi Arabia - Project number BA-24 029
Almuntashiri et al. (Fri,) studied this question.