AbstractBackground and Research QuestionThe host response plays a central role in the pathophysiology of sepsis and severe injuries. So far, no study has comprehensively described the overtime changes of the injury-induced immune profile in a large cohort of critically ill patients with different etiologies.Study Design and Methods353 septic, trauma and surgical patients and 175 healthy volunteers were prospectively included in the REAnimation Low Immune Status Marker (REALISM) study. Extensive immune profiling was performed by assessing cellular phenotypes and functions, protein and mRNA levels at days 1-2, 3-4 and 5-7 after inclusion using a panel of 30 standardized immune markers.ResultsUsing REALISM immunomonitoring panel, no specificity in the immune profile was observed between septic, trauma and surgical patients. This common injury-induced immune response was characterized by an initial adaptive (i.e. physiologic) response engaging all constituents of the immune system (pro- and anti-inflammatory cytokine release, innate and adaptive immune responses) but not associated with increased risk of secondary infections. In contrary, the persistence in a subgroup of patients of profound immune alterations at the end of the first week after admission was associated with increased risk of secondary infections independently of exposure to invasive devices. The combined monitoring of markers of pro/anti-inflammatory, innate and adaptive immune responses allowed a better enrichment of patients with risk of secondary infections in the selected population.InterpretationThese results illustrate the delayed development of a common maladaptive injury-acquired immunodeficiency in a subgroup of severely injured patients independently of initial etiologies. Critically ill patients’ immune status could be captured through the combined monitoring a common panel of complementary markers of pro/anti-inflammatory, innate and adaptive immune responses. Such immune monitoring panel will help clinicians to identify critically ill patients who could benefit from tailored immunoadjuvant therapies.Clinical Trial Registrationclinicaltrials.gov: NCT02638779Summary conflict of interest statementsJT, SB, VM and AP are employees of bioMérieux SA, an in vitro diagnostic company. FV, TR, YB, BD, OM, TG, CT and GM are employees of Hospices Civils de Lyon. JT, TR, SB, VM, AP, FV and GM work in a joint research unit, co funded by the Hospices Civils de Lyon and bioMérieux. JT, AP, GM and FV are co-inventors in patent applications covering the following markers: CX3CR1, CD127, IL10 and S100A9. LKT and CT are employees of and hold stock and shares in GlaxoSmithKline. LQU is an employee of Sanofi Pasteur. PC was employee of Sanofi, Inc. and declares no other competing interests.Funding informationThis study received funding from the Agence Nationale de la Recherche through a grant awarded to BIOASTER (Grant number #ANR-10-AIRT-03) and from bioMérieux, Sanofi and GSK.
Identification of risk and protective human leukocyte antigens in COVID-19 using genotyping and structural modeling
