SARS-CoV-2-induced IgG repertoires shape T cell responses, microRNA regulation, and autoreactivity according to disease severity

SARS-CoV-2 infection can generate IgG repertoires with functions beyond viral neutralization. We purified IgG from non-exposed healthy controls, moderate and severe COVID-19 patients, and IVIg, and assessed their effects on healthy-donor PBMCs. COVID-19 IgG bound CD4+ and CD8+ T cells without inducing apoptosis. Severe-COVID IgG reduced Treg frequencies, enhanced IFN-γ production, and expanded autoreactivity toward proteins linked to proteostasis, whereas moderate-COVID IgG promoted CD8+ IL-22 and selective miRNA downregulation. These findings identify disease-severity-associated antibody-mediated immune modulation in vitro and motivate patient-resolved longitudinal validation.