AUTHOR=Pesce Elisa , Manfrini Nicola , Cordiglieri Chiara , Santi Spartaco , Bandera Alessandra , Gobbini Andrea , Gruarin Paola , Favalli Andrea , Bombaci Mauro , Cuomo Alessandro , Collino Federica , Cricrì Giulia , Ungaro Riccardo , Lombardi Andrea , Mangioni Davide , Muscatello Antonio , Aliberti Stefano , Blasi Francesco , Gori Andrea , Abrignani Sergio , De Francesco Raffaele , Biffo Stefano , Grifantini Renata 

TITLE=Exosomes Recovered From the Plasma of COVID-19 Patients Expose SARS-CoV-2 Spike-Derived Fragments and Contribute to the Adaptive Immune Response

JOURNAL=Frontiers in Immunology

VOLUME=Volume 12 - 2021

YEAR=2022

URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2021.785941

DOI=10.3389/fimmu.2021.785941

ISSN=1664-3224

ABSTRACT=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 exosomes recovered from the plasma 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 exosomes 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 exosomes recovered from the plasma 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.