While previous studies have identified DHF biomarkers, our dual-seropositive patients showed overlapping proteins and unique TGF-β signaling and complement activation, highlighting novel ADE–autoantibody synergy, where SARS-CoV-2 exposure creates vascular leakage via THBS1 and STXBP5 as “second hits”. The gene discussed is STXBP5; the disease is acute disseminated encephalomyelitis.