Mikuteit Marie, Baskal Svetlana, Klawitter Sandra, Dopfer-Jablonka Alexandra, Behrens Georg M N, Müller Frank, Schröder Dominik, Klawonn Frank, Steffens Sandra, Tsikas Dimitrios
Department of Rheumatology and Immunology, Hannover Medical School, Hannover, Germany.
Hannover Medical School, Dean's Office-Curriculum Development, Hannover, Germany.
Amino Acids. 2023 Sep;55(9):1173-1188. doi: 10.1007/s00726-023-03305-1. Epub 2023 Jul 29.
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-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.
在本研究中，我们调查了2022年收集的长新冠（LoCo，n = 124）和康复新冠（ExCo，n = 24）人类受试者血清和尿液样本中氨基酸的状态、其翻译后修饰（PTM）、主要一氧化氮（NO）代谢物以及作为氧化应激生物标志物的丙二醛（MDA）。使用稳定同位素标记类似物作为内标，通过气相色谱 - 质谱（GC-MS）方法测量氨基酸和代谢物。循环和排泄的精氨酸及不对称二甲基精氨酸（ADMA）方面没有差异。LoCo参与者排泄的胍基乙酸量高于ExCo参与者（17.8±10.4 μM/mM对12.6±8.86 μM/mM，P = 0.005）。相比之下，LoCo参与者排泄的晚期糖基化终产物（AGE）N - 羧乙基精氨酸（CEA）量低于ExCo参与者（0.675±0.781 μM/mM对1.16±2.04 μM/mM，P = 0.0326）。两组之间MDA的血清浓度没有差异，表明LoCo或ExCo中氧化应激没有升高。LoCo的血清亚硝酸盐浓度低于ExCo（1.96±0.92 μM对2.56±1.08 μM；AUC，0.718），表明内皮中NO合成改变。血清亚硝酸盐浓度与症状焦虑呈负相关（r = - 0.293，P = 0.0003）。肌酐校正后的赖氨酸及其代谢物L - 5 - 羟基赖氨酸的尿排泄量与新冠脚趾（r = 0.306，P = 0.00027）和喉咙痛（r = 0.302，P = 0.0003）呈正相关。我们的结果表明，长新冠中氨基酸代谢、PTM和氧化应激没有受到严重影响。LoCo参与者的循环NO储备可能低于ExCo。
