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.