The ability of exosomes from MILD COVID-19 patients to act as strong stimulators of CD4+ T-cell activation and growth was confirmed by their proteome cargos, which were related to immune response, cell growth, signal transduction, and MHC class II receptor functionality; in contrast, exosomes derived from SEVERE COVID-19 patient correlated with immune/inflammatory responses (such as regulators of IL-6 proinflammatory signaling), members of the coagulation system, and protein metabolism functions. This evidence concerns the gene CD4 and COVID-19.