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

• Published in: Frontiers in immunology Vol. 12; p. 785941
• Main Authors: 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
• Format: Journal Article
• Language: English
• Published: Switzerland Frontiers Media S.A 17-01-2022
• Subjects: Acute Disease; Adaptive Immunity; Adult; Aged; antigen-presenting cells (APCs); COVID-19; COVID-19 - blood; COVID-19 - immunology; exosomes; Exosomes - immunology; Exosomes - metabolism; Female; Humans; immune activation; Immunology; Male; Middle Aged; Plasma; SARS-CoV-2; SARS-CoV-2 - immunology; SARS-CoV-2 - metabolism; soluble mediators in immunity; Spike Glycoprotein, Coronavirus - blood; Spike Glycoprotein, Coronavirus - immunology; COVID-19; SARS-CoV-2; soluble mediators in immunity; antigen-presenting cells (APCs); exosomes; immune activation
• ISSN: 1664-3224; 1664-3224
• DOI: 10.3389/fimmu.2021.785941

Coronavirus disease 2019 (COVID-19) is an infectious disease caused by beta-coronavirus severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that 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 of efficiently regulating 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 that reflects the pathological state of patients in the acute phase of the disease.