Exosomes recovered from the plasma of COVID-19 patients have an active role in enhancing the immune response

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.

Researchers at the INGM, Italy performed a comparative study on exosomes recovered from the plasma of either MILD or SEVERE COVID-19 patients. They 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, the researchers 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.

Imaging analysis confirms the increased presence of SARS-CoV-2-S on the surface of exosomes recovered from MILD COVID-19 patients

(A) STED analysis of SARS-CoV-2-S expression in bead-captured exosomes. (B) Scheme of TEM sample preparation via suspension-stained sample dripping onto carbon-coated Formavar grids. No embedding nor cutting was performed. (C) Representative TEM micrographs at lower and higher magnification of anti-SARS-CoV-2-S-RBD*gold labeled exosomes recovered from plasma of HD (upper row) or MILD (middle row left and lower enlarged image) or SEVERE (middle row right) COVID-19 patients immunocaptured with lattice beads. (D) Scheme of single-molecule localization microscopy via TRF/direct-STORM on conjugated immunolabeled RBD on the surface of exosomes recovered from MILD COVID-19 patient plasma, immunocaptured via lattice beads. (E) Diffracted-limited widefield image of one representative autofluorescent bead (contoured by magenta dotted circle) capturing several af647-RBD-labeled exosomes. (F) STORM acquisition and reconstruction of blinking af647-anti-RBD molecules from the chosen bead shown in panel (D) (G) 3D-STORM acquisition and reconstruction with x, y, z coordinates of single molecule localization within the TIRF plan for 3D view of a representative MILD COVID-19 plasma-recovered exosome immunolabeled for RBD. 

Pesce E, Manfrini N, Cordiglieri C, Santi S, Bandera A, Gobbini A, Gruarin P, Favalli A, Bombaci M, Cuomo A, Collino F, Cricrì G, Ungaro R, Lombardi A, Mangioni D, Muscatello A, Aliberti S, Blasi F, Gori A, Abrignani S, De Francesco R, Biffo S, Grifantini R. (2022) Exosomes Recovered From the Plasma of COVID-19 Patients Expose SARS-CoV-2 Spike-Derived Fragments and Contribute to the Adaptive Immune Response. Front Immunol 12:785941. [article]

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