Role of RNA Metabolism Alterations in Persistent Immune Dysfunction After Sepsis

Rôle Des Altérations Du Métabolisme De L'ARN Dans La Persistance Des Perturbations Immunitaires Au Décours Du Sepsis

This study includes adult ICU patients with sepsis (according to SEPSIS 3.0) or critically ill non-septic patients with severe non-infectious conditions at Louis Mourier Hospital. It is a prospective multicentre observational study aiming to describe leukocyte transcriptome changes and molecular trajectories (endotypes) during the acute, recovery, and convalescence phases of sepsis. A total of 290 participants will be included: 200 septic patients, 50 critically ill non-septic patients, and 40 control participants.

The study will be a prospective, multicentre, observational study including adult ICU patients hospitalized with sepsis (according to SEPSIS 3.0 definitions) or critically ill non-septic patients with severe non-infectious conditions at Louis Mourier Hospital.

Participants will be assigned to one of three groups:

• Septic patients group: 200 patients with suspected or documented infection and a SOFA score ≥2.
• Critically ill non-septic patients group: 50 patients without infection and a SOFA score ≥2.
• Control group: 40 ambulatory participants without infection, matched for age and sex.

Blood samples for transcriptome and immunomonitoring analyses will be collected at predefined time points during ICU stay and post-ICU follow-up (J1, J3, J7, J14, M3, M6, M12). Routine clinical and laboratory parameters will also be recorded.

The primary objective is to describe longitudinal molecular trajectories (endotypes) of circulating leukocytes over the natural course of sepsis. The primary endpoint is the identification of molecular endotypes from sequential transcriptome analyses.

Secondary analyses will compare molecular profiles between septic and non-septic patients, evaluate the effects of alternative splicing on the cellular proteome, and correlate endotypes with clinical outcomes during ICU stay and up to 12 months post-inclusion. Bioinformatic methods (JLCMM, KmL) and pathway analysis (Ingenuity Pathway Analysis, Qiagen) will be used to identify patient groups with similar molecular profiles over time.

- Septic patients group: Age ≥ 18 years Hospitalized in Intensive Care Medicine Suspected or confirmed infection SOFA score ≥ 2

- Critically ill non-septic patients group: Age ≥ 18 years Hospitalized in Intensive Care Medicine No infection (neither suspected nor confirmed) SOFA score ≥ 2

- Healthy control group Age ≥ 18 years Ambulatory patient (not hospitalized) No infection at the time of consultation