Persistent mitochondrial and endothelial dysfunction in non-hospitalized patients with Long COVID

Long COVID, a major post-acute infection syndrome (PAIS), characterized by prolonged or new-onset symptoms following acute COVID-19, critically affects patients' quality of life. Establishing easily measurable and objective biomarkers that reflect disease severity is essential for clinical management. This retrospective cohort study evaluated serum levels of growth differentiation factor 15 (GDF-15), a mitochondrial stress marker, and vascular cell adhesion molecule-1 (VCAM-1), a vascular endothelial stress marker, in 32 patients with Long COVID who presented with persistent systemic or neurological symptoms and had not required acute-phase hospitalization. Serum GDF-15, VCAM-1, and inflammatory cytokine levels were measured at the initial visit and at 3 and 6 months. Differences between patients who recovered at 6 months and those who did not (non-improved group) were analyzed using linear mixed-effects models (LMMs). Most inflammatory cytokines remained near their lower detection limits and were excluded from the longitudinal analysis. The LMMs revealed sustained elevation of both GDF-15 ( p = 0.02) and VCAM-1 ( p = 0.03) levels in the non-improved group. These findings suggest that longitudinal tracking of these two markers may offer clinically relevant insights into disease activity and treatment-resistant pathophysiology in mild acute-phase Long COVID.