Abstract 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 (P0.001). 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. This abstract is funded by: FAPDF
Araujo et al. (Fri,) studied this question.