Serum-derived extracellular vesicles: Novel biomarkers reflecting the disease severity of COVID-19 patients.

COVID-19 is characterized by a wide spectrum of disease severity, whose indicators and underlying mechanisms need to be identified. The role of extracellular vesicles (EVs) in COVID-19 and their biomarker potential, however, remains largely unknown. Aiming to identify specific EV signatures of patients with mild compared to severe COVID-19, we characterized the EV composition of 20 mild and 26 severe COVID-19 patients along with 16 sex and age-matched healthy donors with a panel of eight different antibodies by imaging flow cytometry (IFCM). We correlated the obtained data with 37 clinical, prerecorded biochemical and immunological parameters. Severe patients' sera contained increased amounts of CD13+ and CD82+ EVs, which positively correlated with IL-6-producing and circulating myeloid-derived suppressor cells (MDSCs) and with the serum concentration of proinflammatory cytokines, respectively. Sera of mild COVID-19 patients contained more HLA-ABC+ EVs than sera of the healthy donors and more CD24+ EVs than severe COVID-19 patients. Their increased abundance negatively correlated with disease severity and accumulation of MDSCs, being considered as key drivers of immunopathogenesis in COVID-19. Altogether, our results support the potential of serum EVs as powerful biomarkers for COVID-19 severity and pave the way for future investigations aiming to unravel the role of EVs in COVID-19 progression.

Extracellular Vesicles and Acute Kidney Injury: Potential Therapeutic Avenue for Renal Repair and Regeneration.

Acute kidney injury (AKI) is a sudden decline of renal function and represents a global clinical problem due to an elevated morbidity and mortality. Despite many efforts, currently there are no treatments to halt this devastating condition. Extracellular vesicles (EVs) are nanoparticles secreted by various cell types in both physiological and pathological conditions. EVs can arise from distinct parts of the kidney and can mediate intercellular communication between various cell types along the nephron. Besides their potential as diagnostic tools, EVs have been proposed as powerful new tools for regenerative medicine and have been broadly studied as therapeutic mediators in different models of experimental AKI. In this review, we present an overview of the basic features and biological relevance of EVs, with an emphasis on their functional role in cell-to-cell communication in the kidney. We explore versatile roles of EVs in crucial pathophysiological mechanisms contributing to AKI and give a detailed description of the renoprotective effects of EVs from different origins in AKI. Finally, we explain known mechanisms of action of EVs in AKI and provide an outlook on the potential clinical translation of EVs in the setting of AKI.