Exosomes Recovered From the Plasma of COVID-19 Patients Expose SARS-CoV-2 Spike-Derived Fragments and Contribute to the Adaptive Immune Response
Elisa Pesce, Nicola Manfrini, Chiara Cordiglieri, Spartaco Santi, Alessandra Bandera, Andrea Gobbini, Paola Gruarin, Andrea Favalli, Mauro Bombaci, Alessandro Cuomo, Federica Collino, Giulia Cricrì, Riccardo Ungaro, Andrea Lombardi, Davide Mangioni, Antonio Muscatello, Stefano Aliberti, Francesco Blasi, Andrea Gori, Sergio Abrignani, Raffaele De Francesco, Stefano Biffo, Renata Grifantini
Abstract
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.