LAUSR

Abstract 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.