Severity-associated endothelial dysfunction in post-COVID-19 patients: flow-mediated dilation and vasoactive...

COVID-19 is frequently associated with endothelial dysfunction, characterized by an imbalance between vasodilatory and vasoconstrictive mediators. This study evaluated endothelial function in the early post-COVID-19 period across groups of acute disease severity using flow-mediated dilation (FMD), circulating vasoactive biomarkers, and echocardiography. Serum endothelin-1 (ET-1), arginase-1 (Arg1), thromboxane A₂ (TxA₂)-related immunoreactivity, and prostacyclin (PGI₂)-related immunoreactivity were measured by enzyme-linked immunosorbent assay. An impaired FMD response was defined as < 10% brachial artery dilation from baseline. Overall, 502 post-COVID-19 patients were classified by acute COVID-19 severity as mild (n = 262), moderate (n = 183), severe (n = 41), or critical (n = 16); 27 healthy individuals served as a reference group. Impaired FMD responses were more frequent after severe (90.24%) and critical (100.00%) disease than in the reference group (18.52%). Greater acute disease severity was associated with progressively lower FMD values, smaller absolute brachial artery diameter changes, higher ET-1, Arg1, and TxA₂-related immunoreactivity, and lower PGI₂-related immunoreactivity. After adjustment for age, sex, body mass index, systolic blood pressure, smoking, diabetes mellitus, pre-existing cardiovascular disease, and post-COVID-19 interval, acute disease severity remained associated with impaired FMD (adjusted odds ratio 3.32, 95% confidence interval 2.29-4.82; p < 0.001 per one-category increase). Biomarker-FMD correlations were generally weak. Among patients assessed during the early post-COVID-19 period, greater acute COVID-19 severity was associated with greater impairment of endothelium-dependent vasodilation and an altered profile of circulating vasoactive biomarkers. These findings indicate associated functional and biochemical vascular abnormalities without establishing causality or a mechanistic relationship. Prospective longitudinal studies are needed to clarify their temporal evolution and clinical significance.