Microvascular Dysfunction and Redox Imbalance in Long COVID.

OBJECTIVE

Endothelial and microvascular dysfunction are key features of Long COVID. Disturbances in cellular redox balance, reflected by altered nicotinamide adenine dinucleotide (NAD+/NADH) dynamics, may underlie vascular impairment. Flow-Mediated Skin Fluorescence (FMSF) evaluates microvascular function by monitoring NADH fluorescence during ischemia and reperfusion. We integrated FMSF-derived microvascular phenotyping with targeted NAD+ metabolite profiling to determine whether altered NAD+ metabolism is associated with impaired microvascular responses in Long COVID.

METHODS

Microvascular function was assessed in 36 patients with Long COVID and 47 age-matched controls using FMSF. NADH fluorescence changes during ischemia and hyperemia were analyzed as markers of endothelial responsiveness. NAD+ and related metabolites were measured using high-performance liquid chromatography and mass spectrometry.

RESULTS

Patients with Long COVID showed impaired FMSF parameters, including blunted ischemic responses and delayed recovery after hyperemia, indicating microvascular dysfunction. These changes were accompanied by a reduced NAD+/NADH ratio and lower NADP levels, consistent with redox imbalance. Abnormal fluorescence profiles were associated with altered NAD+ metabolism, including reduced precursor availability and accumulation of degradation products. Higher NR concentrations showed associations with selected microvascular and eNOS-related parameters.

CONCLUSIONS

FMSF provides a clinically applicable tool for detecting microvascular dysfunction in Long COVID. NAD+ redox imbalance is linked to impaired microcirculatory responses, supporting FMSF as a functional marker of microvascular impairment associated with altered NAD+ metabolism.