Chronic Critical Illness Elicits a Unique Circulating Leukocyte Transcriptome in Sepsis Survivors

Area of Science:

• Immunology
• Genomics
• Critical Care Medicine

Background:

• Sepsis presents distinct patient trajectories, including rapid recovery and chronic critical illness (CCI).
• Understanding the molecular differences between these sepsis outcomes is crucial for targeted interventions.

Purpose of the Study:

• To investigate if sepsis survivors who develop CCI exhibit unique blood leukocyte transcriptomes in late sepsis.
• To compare the transcriptomic profiles of CCI sepsis survivors with those who experience rapid recovery.

Main Methods:

• Prospective cohort study of surgical intensive care unit (ICU) patients.
• Genome-wide expression analysis of total leukocytes from whole blood.
• Samples collected on days 1 and 14 from sepsis survivors with rapid recovery or CCI (ICU stay ≥ 14 days with persistent organ dysfunction).

Main Results:

• Both CCI and rapid recovery sepsis survivors showed significant genome-wide expression changes from day 1 through day 14.
• CCI patients displayed differential expression of 185 unique genes compared to rapid recovery patients at day 14 (p < 0.001).
• Transcriptomic patterns indicate persistent immune dysregulation, including inflammation and immunosuppression, in CCI survivors.

Conclusions:

• Sepsis survivors, particularly those with CCI, exhibit persistent immune dyscrasia at the blood leukocyte transcriptome level.
• Specific gene expression patterns in CCI survivors may serve as prognostic markers.
• Identified genes represent potential therapeutic targets for managing chronic critical illness in sepsis.