miRNome profiling of extracellular vesicles in severe COVID-19 patients and identification of predictors of mortality.

ABSTRACT

BACKGROUND: Extracellular vesicles (EVs), containing microRNAs (miRNAs) and other molecules, play a central role in intercellular communication, especially in viral infections caused by SARS-CoV-2. This study explores the miRNA profiles in plasma-derived EVs from severe COVID-19 patients referred to controls, identifying potential mortality miRNA predictors. METHODS: A prospective study was carried out, including 36 severe COVID-19 patients and 33 non-COVID-19 controls. EVs-derived miRNAs were sequenced, and bioinformatics and differential expression analysis between groups were performed. The plasma miRNA profile of an additional cohort of severe COVID-19 patients (n=32) and non-COVID-19 controls (n=12) was used to compare with our data. Survival analysis was used to identify potential mortality predictors among the SDE miRNAs in EVs. RESULTS: Severe COVID-19 patients showed 50 significantly differentially expressed (SDE) miRNAs in plasma-derived EVs. These miRNAs were associated with pathways related to inflammation and cell adhesion. Fifteen of these plasma-derived EVs miRNAs were also SDE in the plasma of severe patients vs controls. Two miRNAs, hsa-miR-1469 and hsa-miR-6124, were identified as strong mortality predictors with an área under the ROC Curve (AUC) of 0.938. CONCLUSION: This research provides insights into the role of miRNAs found within EVs in severe COVID-19 and their potential as clinical biomarkers for mortality.