Endothelial extracellular vesicles enriched in microRNA-34a predict new-onset diabetes in COVID-19 patients: novel insights for long-COVID metabolic sequelae

: Emerging evidence indicates that the relationship between COVID-19 and diabetes is twofold: 1) it is known that the presence of diabetes and other metabolic alterations poses a considerably high risk to develop a severe COVID-19; 2) patients who survived a SARS-CoV-2 infection have an increased risk of developing new-onset diabetes. However the mechanisms underlying this association are mostly unknown and there are no reliable biomarkers to predict the development of new-onset diabetes. In the present study, we demonstrate that a specific microRNA (miR-34a) contained in circulating extracellular vesicles released by endothelial cells reliably predicts the risk of developing new-onset diabetes in COVID-19. This association was independent of age, sex, BMI, hypertension, dyslipidemia, smoking status, and D-dimer. Significance Statement We demonstrate for the first time that a specific microRNA (miR-34a) contained in circulating extracellular vesicles released by endothelial cells is able to reliably predict the risk of developing new-onset diabetes mellitus after having contracted COVID-19. Strikingly, this association was independent of age, sex, BMI, hypertension, dyslipidemia, smoking status, and D-dimer. Our findings are also relevant when considering the emerging importance of post-acute sequelae of COVID-19, with systemic manifestations observed even months after viral negativization (Long-COVID).