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Persistent endothelial dysfunction is associated with exercise intolerance in adults despite preserved myocardial work 3 years after SARS-CoV-2 infection.

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Title: Persistent endothelial dysfunction is associated with exercise intolerance in adults despite preserved myocardial work 3 years after SARS-CoV-2 infection.
Authors: de Araújo Alves CC; Laboratory of Clinical Exercise Physiology, FCE, University of Brasília (UnB), Brasília, DF, Brazil., Goulart CDL; Laboratory of Clinical Exercise Physiology, FCE, University of Brasília (UnB), Brasília, DF, Brazil.; Internal Medicine Department, Federal University of Rio Grande Do Sul (UFRGS), Porto Alegre, RS, Brazil., D'Ávila L; Laboratory of Clinical Exercise Physiology, FCE, University of Brasília (UnB), Brasília, DF, Brazil., de Souza Silva BHE; Laboratory of Clinical Exercise Physiology, FCE, University of Brasília (UnB), Brasília, DF, Brazil., Alves IM; Laboratory of Clinical Exercise Physiology, FCE, University of Brasília (UnB), Brasília, DF, Brazil., Aguiar BVS; Laboratory of Clinical Exercise Physiology, FCE, University of Brasília (UnB), Brasília, DF, Brazil., Conde C; Laboratory of Clinical Exercise Physiology, FCE, University of Brasília (UnB), Brasília, DF, Brazil., Stein R; Internal Medicine Department, Federal University of Rio Grande Do Sul (UFRGS), Porto Alegre, RS, Brazil.; Exercise Cardiology Research Group, Hospital de Clínicas de Porto Alegre (CardioEx-HCPA), Porto Alegre, RS, Brazil., Cipriano G Jr; Laboratory of Clinical Exercise Physiology, FCE, University of Brasília (UnB), Brasília, DF, Brazil.
Source: Physiological reports [Physiol Rep] 2026 Oct; Vol. 14 (19), pp. e71103.
Publication Type: Journal Article
Language: English
Journal Info: Publisher: published by Wiley Periodicals, Inc. on behalf of the American Physiological Society and The Physiological Society Country of Publication: United States NLM ID: 101607800 Publication Model: Print Cited Medium: Internet ISSN: 2051-817X (Electronic) Linking ISSN: 2051817X NLM ISO Abbreviation: Physiol Rep Subsets: MEDLINE
Imprint Name(s): Original Publication: [Malden MA] : published by Wiley Periodicals, Inc. on behalf of the American Physiological Society and The Physiological Society, 2013-
MeSH Terms: Endothelium, Vascular*/physiopathology , Exercise Tolerance*/physiology , COVID-19*/physiopathology , COVID-19*/complications, Brachial Artery/physiopathology ; Humans ; Male ; Female ; Middle Aged ; Post-Acute COVID-19 Syndrome ; Case-Control Studies ; Exercise Test ; Adult ; Global Longitudinal Strain ; Oxygen Consumption ; Vasodilation ; Echocardiography
Abstract: 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 V̇O2 (19.6 ± 2.5 vs. 24.3 ± 6.5 mL·kg-1·min-1, p = 0.04), percent-predicted peak V̇O2 (61.1 ± 8.3 vs. 77.0 ± 14.2%, p = 0.006), and V̇O2 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 V̇O2: r = 0.68, p = 0.03;percent-predicted peak V̇O2: 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.
(© 2026 The Author(s). Physiological Reports published by Wiley Periodicals LLC on behalf of The Physiological Society and the American Physiological Society.)
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Contributed Indexing: Keywords: Long COVID; brachial flow‐mediated dilation; exercise tolerance; myocardial work; vascular endothelium
Entry Date(s): Date Created: 20260929 Date Completed: 20260929 Latest Revision: 20261001
Update Code: 20261001
DOI: 10.14814/phy2.71103
PMID: 42810981
Database: MEDLINE
Description
ISSN:2051-817X
DOI:10.14814/phy2.71103