C97-03 Persistent Endothelial Dysfunction and Impaired Hyperemia in Long COVID With Exercise Intolerance Three Years After Infection

Rationale Long COVID is characterized by persistent symptoms and reduced exercise capacity. Endothelial dysfunction has been proposed as a central mechanism underlying these sequelae. Flow-mediated dilation (FMD) of the brachial artery provides a noninvasive, clinically relevant index of endothelial function. However, data regarding endothelial status beyond two years after infection remain scarce. Methods Observational case-control study conducted in 2023-2024. Adults with Long COVID and cardiopulmonary exercise testing (CPET)-confirmed exercise intolerance (VO2peak <70% predicted), 3 years post-infection. Participants underwent clinical profiling, CPET, transthoracic echocardiography including longitudinal strain (GLS) and myocardial work (MW) indices, and brachial-artery FMD with reactive hyperemia assessment. Group differences, effect sizes (Cohen’s D), and correlations were analyzed with P < 0.05 considered significant. Results Twenty-two participants completed the study (Long COVID n = 10; controls n = 12). At baseline individuals with Long COVID presented with higher BMI (32.9±4.5 vs 28.2±3.8 kg·m⁻²; P = 0.01) and reported depressive symptoms more frequently (30% vs 0%; P = 0.04). All participants with Long COVID reported at least one persistent symptom, most commonly fatigue (60%), exercise intolerance (50%) and dyspnea (40%). Functional status, assessed by Post-COVID-19 Functional Status scale (PCFS), was worse in the Long COVID group (P<0.001). Individuals with Long COVID demonstrated reduced exercise capacity, as indicated by lower peak oxygen uptake (VO2peak; 20.0±3.3 vs 24.3±6.5 mL·kg⁻¹·min⁻¹; d = 0.64; P=0.04; VO2peak as a % of the predicted value) 61.1±8.3 vs 77.0±14.2 %; d = 1.33; P=0.006; and VO2 at the ventilatory threshold 1 (VT1); 11.0±1.4 vs 13.7±3.8 mL·kg⁻¹·min⁻¹; d = 0.91; P=0.04. Echocardiographic structure and function were preserved in both groups, with no significant differences in conventional parameters, GLS, or MW indices (all P > 0.05). In contrast, endothelial function was impaired in Long COVID participants, evidenced by lower flow mediated dilatation (FMD 5.4±1.6 vs 7.9±1.1 %; d = 1.10; P < 0.001). The hyperemic stimulus was also attenuated with lower peak shear rate (578±161 vs 958±465 s⁻¹; d = 1.02; P=0.02) and area under the curve of shear rate (7576± 3865 vs 14647±5924 s⁻¹; d = 1.17; P=0.004). Conclusion Three years after the acute phase, individuals with Long COVID and CPET-confirmed exercise intolerance continue to exhibit endothelial dysfunction and an attenuated hyperemic response. These findings suggest that, at this late post-COVID stage, exercise intolerance is primarily driven by peripheral vascular rather than central cardiac limitation.