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Updated: Jun 12, 2025

Non-invasive Assessment of Microvascular and Endothelial Function
Published on: January 29, 2013
Follow-up assessment of the microvascular function in patients with long COVID
Marzena Romanowska-Kocejko1, Alicja Braczko2, Agata Jędrzejewska2
1Department of Cardiac Diagnostics, Medical University of Gdansk, Poland.
Insights
Long COVID impairs microvascular function, evidenced by flow-mediated skin fluorescence (FMSF) tests. This dysfunction improved after three months, particularly with cardioprotective therapy, indicating FMSF
Area of Science:
- Cardiovascular Science
- Microcirculation Research
- Long COVID Pathophysiology
Background:
- Long COVID is increasingly recognized as a systemic condition involving microvascular endothelial dysfunction.
- Understanding the mechanisms and measurable indicators of this dysfunction is crucial for effective management.
- Previous studies suggest a link between COVID-19 and impaired circulatory function.
Purpose of the Study:
- To assess microvascular function in long COVID patients using the flow-mediated skin fluorescence (FMSF) technique.
- To investigate the correlation between biochemical markers (L-arginine derivatives, HIF1α) and microvascular parameters.
- To evaluate the recovery of microcirculatory function over a three-month period, especially with therapeutic interventions.
Main Methods:
- Flow-mediated skin fluorescence (FMSF) was used to measure ischemic response (IR) and hyperemic response (HR) in 33 long COVID patients and 30 controls.
- Measurements were repeated after three months.
- Serum levels of L-arginine derivatives and hypoxia-inducible factor 1α (HIF1α) were quantified and correlated with FMSF parameters.
Main Results:
- Long COVID patients exhibited impaired microvascular function (lower/negative IR parameters) compared to controls.
- Serum HIF1α correlated negatively with IR index, and asymmetric dimethyl-L-arginine correlated negatively with HRmax and HR index.
- Microcirculatory function improved significantly after three months, with notable recovery in hypoxia sensitivity in patients receiving ACE-inhibitors and beta-blockers.
Conclusions:
- Flow-mediated skin fluorescence (FMSF) is a sensitive, non-invasive method for assessing microvascular dysfunction in long COVID.
- Microvascular function impairment in long COVID can recover over time, particularly with targeted cardioprotective therapies.
- The study highlights the role of endothelial dysfunction in long COVID and the potential of FMSF for monitoring treatment efficacy.
Abstract:
Long COVID is a complex pathophysiological condition. However, accumulating data suggests that COVID-19 is a systemic microvascular endothelial dysfunction with different clinical manifestations. In this study, a microvascular function was assessed in long COVID patients (n = 33) and healthy controls (n = 30) using flow-mediated skin fluorescence technique (FMSF), based on measurements of nicotinamide adenine dinucleotide fluorescence intensity during brachial artery occlusion (ischemic response, IR) and immediately after occlusion (hyperemic response, HR). Microcirculatory function readings were taken twice, 3 months apart. In addition, we quantified biochemical markers such as the serum L-arginine derivatives and hypoxia-inducible factor 1α (HIF1α) to assess their relation with microvascular parameters evaluated in vivo. In patients with long COVID, serum HIF1α was significantly correlated to IRindex (r = -0.375, p < 0.05). Similarly, there was a significant inverse correlation of serum asymmetric dimethyl-L-arginine levels to both HRmax (r = -0.343, p < 0.05) and HRindex (r = -0.335, p < 0.05). The IR parameters were found lower or negative in long COVID patients and recovered in three-month follow-up. Hypoxia sensitivity value was significantly higher in long COVID patients examined after three months of treatment based on the combination of ACE-inhibitors and beta-adrenolytic compared to baseline condition (85.2 ± 73.8 vs. 39.9 ± 51.7 respectively, p = 0.009). This study provides evidence that FMSF is a sensitive, non-invasive technique to track changes in microvascular function that was impaired in long COVID and recovered after 3 months, especially in patients receiving a cardioprotective therapy.

