de Araujo Alves CC; Laboratory of Clinical Exercise Physiology, Brazil
Goulart CDL; D’Avila L; de Souza Silva et al

Physiological Reports. 14(19):e71103, 2026 Oct. VI 1

Long COVID is frequently associated with persistent exercise intolerance,
although the relative contributions of peripheral vascular dysfunction and
myocardial function remain unclear. We investigated whether persistent
endothelial dysfunction and altered myocardial work (MW) contribute to
exercise intolerance approximately 3 years after SARS-CoV-2 infection.
This case-control study included adults with Long COVID (n = 10) and
controls (n = 11) who underwent cardiopulmonary exercise testing (CPET),
transthoracic echocardiography with global longitudinal strain (GLS) and
MW analysis, and brachial artery flow-mediated dilation (FMD) with
hyperemic shear assessment. Compared with controls, Long COVID
participants exhibited lower peak VO2 (19.6 +/- 2.5 vs. 24.3 +/- 6.5
mL.kg-1.min-1, p = 0.04), percent-predicted peak VO2 (61.1 +/- 8.3 vs.
77.0 +/- 14.2%, p = 0.006), and VO2 at first ventilatory threshold (11.0
+/- 1.4 vs. 13.7 +/- 3.8 mL.kg-1.min-1, p = 0.04). Conventional
echocardiographic parameters and MW indices did not differ between groups
(all p > 0.05). In contrast, endothelial function was impaired in the Long
COVID group, with lower FMD (p < 0.001), peak shear rate (p = 0.01), AUCSR
(p = 0.04), and AUCmax (p = 0.001). FMD correlated positively with
exercise capacity in the Long COVID group (peak VO2: r = 0.68, p =
0.03;percent-predicted peak VO2: r = 0.64, p = 0.04). In conclusion, 3
years after infection, Long COVID remains characterized by endothelial
dysfunction and blunted hyperemic shear despite preserved MW, supporting a
predominantly peripheral vascular basis for persistent exercise
intolerance.