o:36003 Extracellular vesicles subtypes in sera of COVID-19 patients as indicators of immune dysregulation and disease severity en ABSTRACT Investigations, the underlying mechanisms, and indicators of COVID‐19 immunopathogenesis are largely missing. Extracellular vesicles (EVs) emerged as key mechanisms of cell‐to cell communication and excellent biomarkers in many infectious and immune‐related diseases. However, their role COVID‐19 is largely unknown. Here we analyzed a set of clinical, biochemical and immunological markers in 46 COVID‐19 patients (20 with mild symptoms, and 26 with severe symptoms) and 16 sex/age‐matched healthy individuals, along with the imaging flow cytometry EVs characterization from donors’ sera. We found an increased number of CD13+ EVs/ml in COVID‐19 patients, and their number was significantly higher in the group of severe patients, along with the number of CD82+ EVs. Additionally, the number of CD13+ EVs positively correlated with the number of inflammatory monocytes and IL‐6‐producing myeloid‐derived suppressor cells (MDSCs) in severe COVID‐19 patients. In contrast, the patients with mild COVID‐19 symptoms displayed an increased number of HLA‐ABC+EVs compared to healthy donors, and significantly higher number of CD24+ EVs, compared to severe COVID‐19 patients. HLA‐DR‐ABC+ EVs and CD24+ EVs predicted positive outcome of COVID‐19, as they negatively correlated with disease severity and accumulation of IL‐10‐producing MDSCs, the mediators of immune paralysis in severe COVID‐19 patients. These results indicate for the first time that EVs in sera are excellent indicators of COVID‐19 pathogenesis and disease progression, but the exact mechanisms underlining EVs actions in COVID‐19 require further investigations. Biomarkers, chronic inflammation and fibrosis, endo‐ and exocytic vesicles in immunity 1552099 10.1002/eji.202170200 2025-03-04T10:02:20.247Z 44 yes 46 Maja Kosanović University of Belgrade, Institute for the Application of Nuclear Energy INEP, Serbia doktor bioloških nauka 0000-0002-1143-1805 Sergej Tomić University of Belgrade, Institute for the Application of Nuclear Energy INEP, Serbia doktor bioloških nauka person 0000-0003-2570-1295 Bernd Giebel Institute for Transfusion Medicine, University Hospital Essen, University of Duisburg‐Essen, Essen, Germany person Alisa Gruden Movsesijan University of Belgrade, Institute for the Application of Nuclear Energy INEP, Serbia doktor bioloških nauka person 0000-0002-3061-5474 Dejan Stevanović Clinical Hospital Center Zemun, Faculty of Medicine, University of Belgrade, Belgrade, Serbia person Dušan Radojević Laboratory for Molecular Microbiology, Institute of Molecular Genetics and Genetic Engineering, University of Belgrade, Belgrade, Serbia person Nataša Ilić University of Belgrade, Institute for the Application of Nuclear Energy INEP, Serbia person Jelena Djokić Laboratory for Molecular Microbiology, Institute of Molecular Genetics and Genetic Engineering, University of Belgrade, Belgrade, Serbia person Tobias Tertel Institute for Transfusion Medicine, University Hospital Essen, University of Duisburg‐Essen, Essen, Germany person application/pdf 1222014 https://phaidrabg.bg.ac.rs/o:36003 no yes 16 70 92000004 11A29 11A2904 11A26 11A32 11A3283 European Journal of Immunology 51 Suppl. 1 WILEY-VCH Verlag GmbH 2021