Follow-up assessment of the microvascular function in patients with long COVID, 2025, Romanowska-Kocejko et al.

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Follow-up assessment of the microvascular function in patients with long COVID
Romanowska-Kocejko; Braczko; Jędrzejewska; Żarczyńska-Buchowiecka; Kocejko; Kutryb-Zając; Hellmann

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.

Highlights
• FMSF is a sensitive technique to track changes in the microvascular function in long COVID.

• FMSF parameters are associated with biochemical endothelial markers showing altered endothelial function after SARS-CoV-2 infection.

• Cardioprotective therapy improve microvascular function in long COVID patients.

Link (Microvascular Research)

 

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Follow on from Red Blood Cell Adenylate Energetics Is Related to Endothelial and Microvascular Function in Long COVID (2024, Biomedicines)

 

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Several methods are now available to study skin microcirculation and aim to quantify blood flow or oxygenation. However, we can assess the changes in tissue biochemistry in vivo using the measurements of a nicotinamide adenine dinucleotide (NADH) fluorescence signal intensity. Indeed, NADH fluorescence is the strongest component of the fluorescence emitted from the human epidermis. Flow-mediated skin fluorescence (FMSF) is a non-invasive optical technique to study microcirculation and metabolic regulation based on the measurements of skin fluorescence intensity. The newly developed FMSF device enables measurement of the changes in epidermis NADH fluorescence over time in response to brachial artery occlusion.

In addition to endothelium-dependent hyperemic response (HR), FMSF allows to assessment of ischemic response (IR) which may reflect tissue sensitivity to hypoxia. Indeed, the epidermis is particularly sensitive to hypoxia. Therefore, such measurements could be of particular interest in long COVID patients.

Thus, the principal aim of this study was to monitor microvascular function in long COVID patients for three months. Additionally, we investigated the relationship between microvascular parameters recorded using FMSF technique and serum soluble biomarkers of endothelial function, such as L-arginine derivatives and a hypoxia-inducible factor 1 alpha (HIF1α) that plays an integral role in the body’s response to hypoxia.

This study enrolled thirty-three consecutive patients with long COVID from the cardiology outpatient clinic in the university hospital in Gdansk. […] The study’s participants experienced persistent symptoms linked with long COVID, while a cohort of healthy individuals with no prior diagnosis of SARS-CoV-2 infection served as controls.