Autoantibody-Driven Monocyte Dysfunction in Post-COVID Syndrome with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome

Post-COVID syndrome (PCS) has emerged as a significant health concern with persisting symptoms. A subset of PCS patients develops severe myalgic encephalomyelitis/chronic fatigue syndrome (pcME/CFS). Dysregulated autoantibodies (AABs) have been implicated in PCS, contributing to immune dysregulation, impairment of autonomous nerve and vascular function. As recently shown in autoimmune diseases, IgG fractions translate disease-specific pathways into various cells. Therefore, we asked whether IgG fractions from PCS patients could be applied in-vitro to identify specific cytokine responses for PCS patients without (nPCS) and with pcME/CSF. To assess this, we have stimulated monocyte cell lines with IgG fractions from PCS patients. Our findings reveal distinct cytokine responses induced by patient derived AABs which are suggested in vascular and immune dysfunction. In contrast to nPCS, pcME/CSF AABs induced enhanced neurotrophic responses, characterized by significant cytokine correlations involving brain-derived neurotrophic factor (BDNF), glial cell-derived neurotrophic factor (GDNF) and tumor necrosis factor superfamily member 14 ( LIGHT). Further, AAB-induced cytokine levels correlate with clinical symptoms. This study emphasizes a contribution of AABs in PCS, in mitigating long-term immune dysregulation, and a need for therapies modulating IgG-induced signaling pathways.