Extracellular vesicle microRNA biomarkers of late post-sepsis survivors

Sepsis is a life-threatening condition with high hospital mortality. Elevated mortality has also been observed in patients after hospital discharge, associated with post sepsis syndrome (PSS), causing systemic impairments and reduced life quality. The etiology of PSS is still not completely known but certainly involves inflammation. Extracellular vesicles (EV) are recognized as a notable mechanism of intercellular communication in inflammatory processes. It has been reported that EV microRNA (miRNA) production patterns during the acute phase of the disease may persist until after sepsis resolution and are associated with PSS. Methods: We employed mass spectrometry and qPCR to characterize the protein and miRNA composition of plasma-derived EVs of 35 patients during sepsis-related hospitalization and after discharge (post-sepsis) for up to three years. Findings: Fifteen differentially expressed EVs miRNAs (DEMiRs) were identified in septic patients compared to the control group. Predictive analyses revealed that these DEMiRs could influence inflammation by modulating pathways mediated by the activation of NF-κB, STAT3, and TLR4. Thirteen miRNAs (-15b-5p, -16-5p, -20a-5p, -25-3p, -27a-3p, -29a-3p, -30d-5p, -93-5p, -146a-5p, -148a -3p, -191-5p, -195-5p, -223-3p) were downregulated in the death group compared to the survivor group and are candidates for serving as prognostic markers of survival in the Intensive Care Unit. The expression of 11 miRNAs (-15b-5p, -16-5p, -21-5p, -25-3p, -27a-3p, -29a-3p, -30d-5p, -93-5p, -146a-5p -195- 5p and -223-3p) was lower one year after ICU discharge than the control group. Interpretation: The miRNAs identified in the present study represent potential biomarkers for the survival prognosis of post-sepsis patients. Six samples were analyzed, which were divided into 2 groups, septic patients who survived (n=3) and septic patients who died (n=3)