Plasma-derived Exosome-Like Vesicles (ELVs) of COVID-19 patients expose SARS-CoV-2-Spike-derived fragments and contribute to the adaptive immune response

COVID-19 is an infectious disease caused by beta-coronavirus SARS-CoV-2 which has rapidly spread across the globe starting from February 2020. It is well established that during viral infection extracellular vesicles become delivery/presenting vectors of viral material. However, studies regarding extracellular vesicle function in COVID-19 pathology are still scanty. Here, we performed a comparative study on plasma-derived Exosome-Like Vesicles (ELVs) of either MILD or SEVERE COVID-19 patients. We show that, although both types of vesicles efficiently display SARS-CoV-2-Spike-derived peptides and carry immunomodulatory molecules, only those of MILD patients are capable to efficiently regulate antigen-specific CD4+ T cell responses. Accordingly, by mass spectrometry we show that the proteome of ELVs of MILD patients correlates with a proper functioning of the immune system, while that of SEVERE patients is associated with increased and chronic inflammation. Overall, we show, that plasma-derived ELVs of COVID-19 patients possess SARS-CoV-2-derived protein material, have an active role in enhancing the immune response and possess a cargo which reflects the pathological state of patients in the acute phase of the disease.