Extracellular vesicles subtypes in sera of COVID-19 patients as indicators of immune dysregulation and disease severity
Kosanović, Maja
Tomić, Sergej
Giebel, Bernd
Gruden Movsesijan, Alisa
Stevanović, Dejan
Radojević, Dušan
Ilić, Nataša
Djokić, Jelena
Tertel, Tobias
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.
engleski
2021
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Biomarkers, chronic inflammation and fibrosis, endo‐ and exocytic vesicles in immunity