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.
Study Type
OBSERVATIONAL
Enrollment
290
Anesthésie
Colombes, France
Médecine Intensive Réanimation -Hôpital Louis Mourier
Colombes, France
Longitudinal leukocyte transcriptomic endotype classification
Classification of patients into longitudinal leukocyte transcriptomic endotypes based on sequential circulating leukocyte RNA sequencing. Endotype membership will be determined using transcriptomic profiling and reported as categorical group assignment over time, including comparison with critically ill non-infected control patients.
Time frame: From Day 1 to Month 12 after sepsis onset
Alternative splicing events in monocytes
Differential splice variant expression in circulating monocytes, measured by RNA sequencing over time in sepsis and control patients.
Time frame: From Day 1 to Month 12 after sepsis onset
ICU length of stay
Length of ICU stay, measured in days from ICU admission to ICU discharge.
Time frame: From ICU admission to ICU discharge
ICU mortality
All-cause mortality during ICU stay, reported as % of patients.
Time frame: From ICU admission to ICU discharge
Nosocomial infections during ICU stay
Percentage of patients with ≥1 nosocomial infection during ICU stay.
Time frame: From ICU admission to ICU discharge
Rehospitalizations within 12 months
Number of rehospitalizations for any cause within 12 months post-ICU discharge.
Time frame: From ICU discharge to 12 months after sepsis diagnosis
New infectious episodes within 12 months
Percentage of patients with ≥1 new infectious episode within 12 months post-ICU discharge.
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Time frame: From ICU discharge to 12 months after sepsis diagnosis
Cardiovascular events within 12 months
Percentage of patients with ≥1 cardiovascular event (MI, stroke, heart failure) within 12 months post-ICU discharge.
Time frame: From ICU discharge to 12 months after sepsis diagnosis
Incidence of clinical complications by longitudinal transcriptomic endotype
Percentage of patients experiencing ≥1 predefined clinical complication according to longitudinal transcriptomic endotype membership.
Time frame: From Day 1 to Month 12 after sepsis onset
Genetic variants associated with longitudinal transcriptomic endotypes
Frequency of selected genetic polymorphisms associated with longitudinal transcriptomic endotype membership, assessed using genome-wide genotyping arrays.
Time frame: From Day 1 to Month 12 after sepsis onset