Key result
Long COVID is linked to ~23% lower serum nitrite versus ex-COVID, suggesting altered NO synthesis.
Cross-Sectional (n=148)
Yes
Long COVID is associated with lower circulating nitrite levels, suggesting altered endothelial nitric oxide synthesis, but not with severe alterations in amino acid metabolism or oxidative stress.
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Reduced nitrite in long COVID may signal endothelial changes; leaves open whether NO pathway targeting warrants prospective trials.
In this study, we investigated the status of amino acids, their post-translational modifications (PTM), major nitric oxide (NO) metabolites and of malondialdehyde (MDA) as a biomarker of oxidative stress in serum and urine samples of long COVID (LoCo, n = 124) and ex COVID (ExCo, n = 24) human subjects collected in 2022. Amino acids and metabolites were measured by gas chromatography–mass spectrometry (GC–MS) methods using stable-isotope labelled analogs as internal standards. There were no differences with respect to circulating and excretory arginine and asymmetric dimethylarginine (ADMA). LoCo participants excreted higher amounts of guanidino acetate than ExCo participants (17.8 ± 10.4 µM/mM vs. 12.6 ± 8.86 µM/mM, P = 0.005). By contrast, LoCo participants excreted lower amounts of the advanced glycation end-product (AGE) N G -carboxyethylarginine (CEA) than ExCo participants did (0.675 ± 0.781 µM/mM vs. 1.16 ± 2.04 µM/mM, P = 0.0326). The serum concentrations of MDA did not differ between the groups, indicating no elevated oxidative stress in LoCo or ExCo. The serum concentration of nitrite was lower in LoCo compared to ExCo (1.96 ± 0.92 µM vs. 2.56 ± 1.08 µM; AUC, 0.718), suggesting altered NO synthesis in the endothelium. The serum concentration of nitrite correlated inversely with the symptom anxiety ( r = − 0.293, P = 0.0003). The creatinine-corrected urinary excretion of Lys and its metabolite L-5-hydroxy-Lys correlated positively with COVID toes ( r = 0.306, P = 0.00027) and sore throat ( r = 0.302, P = 0.0003). Our results suggest that amino acid metabolism, PTM and oxidative stress are not severely affected in long COVID. LoCo participants may have a lower circulating NO reservoir than ExCo.
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Mikuteit et al. (2023) conducted a cross-sectional in Long COVID (n=148). Long COVID vs. Ex COVID was evaluated on Serum concentration of nitrite (µM) (p=0.0006). Long COVID participants had lower serum nitrite concentrations compared to ex-COVID participants (1.96 vs 2.56 µM), suggesting altered nitric oxide synthesis in the endothelium.
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