Temporal Immune Trajectory and Candidate Biomarkers in Sepsis Associated with Community-Acquired Pneumonia: A Systematic Review
DOI:
https://doi.org/10.48048/tis.2026.13450Keywords:
Community-acquired pneumonia, Sepsis, Transcriptomic, BiomarkerAbstract
Community-acquired pneumonia (CAP) with sepsis remains a leading cause of morbidity and mortality worldwide. Although numerous immune biomarkers have been proposed, integrated evidence describing how immune responses evolve in CAP-associated sepsis is limited, particularly from blood transcriptomic studies. This systematic review aimed to synthesize evidence on temporal immune trajectories and identify candidate transcriptomic biomarkers associated with outcomes in CAP-associated sepsis. A systematic search of medRxiv, PubMed, and CENTRAL was conducted for studies reporting serial blood transcriptomic or immune biomarker data in adult patients with CAP-associated sepsis. Studies with clearly defined timepoints and clinical outcomes were included. Risk of bias was assessed using an adapted Newcastle-Ottawa Scale with transcriptomic-specific criteria. Due to heterogeneity in study design and timing definitions, findings were integrated using structured narrative synthesis. Six studies met the inclusion criteria. Early sepsis was characterized by consistent upregulation of innate inflammatory pathways, including neutrophil activation, interferon-related genes, and cytokine signaling, largely independent of pathogen type. Survivors demonstrated recovery of antigen presentation and adaptive immune pathways at later time points, whereas non-survivors exhibited persistent inflammatory signatures, impaired lymphocyte-associated transcription, immune checkpoint activation, and endothelial dysfunction. Recurrent candidate biomarkers included inflammatory gene signatures, immune endotype classifications, and transcriptomic indicators of adaptive immune suppression. CAP-associated sepsis follows dynamic immune trajectories rather than a single inflammatory state. Temporal transcriptomic patterns may help identify patients at risk of immune failure and guide immunomodulatory strategies. However, heterogeneity in timing definitions, small sample sizes, and limited validation underscore the need for prospective studies before clinical implementation.
HIGHLIGHTS
- This systematic review analyzed defined temporal immune trajectories in CAP-associated sepsis using blood transcriptomic studies.
- Early hyperinflammation was pathogen-independent and not predictive of mortality.
- Failure of antigen presentation and Th1 immunity characterized poor outcomes.
- Immune checkpoint activation and endothelial dysfunction defined immunoparalysis in non-survivors.
- Candidate transcriptomic biomarkers reflect immune competence and exhaustion.
GRAPHICAL ABSTRACT
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