D2.429 - Virus-Specific Regulatory T-Cell Dysregulation in Post-COVID-19 and EBV-Associated Vasculitis

Vasculitic manifestations emerging after viral infections  often persist despite viral clearance. Failure of immune regulation, rather than direct viral injury, contributes to sustained vascular inflammation. Regulatory T cells (Tregs) are central to immune tolerance and endothelial stability, yet their involvement in virus-associated vasculitis is insufficiently explored. This study compares regulatory T-cell activity and immune remodeling in post-COVID-19 cutaneous vasculitis and in secondary systemic vasculitis associated with active Epstein–Barr virus (EBV) replication.

Patients with post-COVID-19 cutaneous vasculitis (n = 26) and EBV-associated secondary systemic vasculitis with PCR-confirmed viremia (n = 32) were investigated using multiparametric flow cytometry. Regulatory T cells were identified as CD4⁺CD25^brightCD127^low/negative lymphocytes. Additional analyses included naïve and memory T-cell subsets, B-cell compartments, NK-cell populations, and T-cell activation markers. Results of these assays were compared with healthy controls (n = 20).

Post-COVID-19 cutaneous vasculitis was associated with a lower proportion of circulating regulatory T cells compared with EBV-associated vasculitis (6.1 ± 1.5% vs 7.3 ± 1.8%, p < 0.05). This reduction coincided with a shift toward memory CD4⁺ T-cell predominance and a relative depletion of naïve CD4⁺ T cells (23.1 ± 6.4% vs 17.9 ± 5.8%, p < 0.01). In contrast, EBV-associated secondary systemic vasculitis showed preserved Treg frequencies but demonstrated signs of sustained immune activation, including reduced memory B-cell pools, expansion of cytotoxic NK-cell subsets (p < 0.01), and higher HLA-DR expression on CD3⁺ T cells (6.9 ± 2.4% vs 5.6 ± 2.1%, p < 0.05).

Post-COVID-19 cutaneous vasculitis is predominantly associated with impaired immunoregulatory control, reflected by quantitative Treg deficiency. In contrast, EBV-associated secondary systemic vasculitis appears to be driven by persistent immune activation involving both adaptive and innate compartments. These distinct immune patterns may support translational stratification and targeted immunomodulatory approaches in virus-associated vasculitis.