Al-Hakeim Hussein Kadhem, Khairi Abed Anwar, Rouf Moustafa Shatha, Almulla Abbas F, Maes Michael
Department of Chemistry, College of Science, University of Kufa, Kufa, Iraq.
Clinical Analysis Department, College of Pharmacy, Hawler Medical University, Erbil, Iraq.
Front Mol Neurosci. 2023 Jun 2;16:1194769. doi: 10.3389/fnmol.2023.1194769. eCollection 2023.
Critical COVID-19 disease is accompanied by depletion of plasma tryptophan (TRY) and increases in indoleamine-dioxygenase (IDO)-stimulated production of neuroactive tryptophan catabolites (TRYCATs), including kynurenine (KYN). The TRYCAT pathway has not been studied extensively in association with the physiosomatic and affective symptoms of Long COVID. In the present study, we measured serum TRY, TRYCATs, insulin resistance (using the Homeostatic Model Assessment Index 2-insulin resistance, HOMA2-IR), C-reactive protein (CRP), physiosomatic, depression, and anxiety symptoms in 90 Long COVID patients, 3-10 months after remission of acute infection. We were able to construct an endophenotypic class of severe Long COVID (22% of the patients) with very low TRY and oxygen saturation (SpO2, during acute infection), increased kynurenine, KYN/TRY ratio, CRP, and very high ratings on all symptom domains. One factor could be extracted from physiosomatic symptoms (including chronic fatigue-fibromyalgia), depression, and anxiety symptoms, indicating that all domains are manifestations of the common physio-affective phenome. Three Long COVID biomarkers (CRP, KYN/TRY, and IR) explained around 40% of the variance in the physio-affective phenome. The latter and the KYN/TRY ratio were significantly predicted by peak body temperature (PBT) and lowered SpO2 during acute infection. One validated latent vector could be extracted from the three symptom domains and a composite based on CRP, KYN/TRY, and IR (Long COVID), and PBT and SpO2 (acute COVID-19). In conclusion, the physio-affective phenome of Long COVID is a manifestation of inflammatory responses during acute and Long COVID, and lowered plasma tryptophan and increased kynurenine may contribute to these effects.
重症新型冠状病毒肺炎（COVID-19）患者伴有血浆色氨酸（TRY）耗竭，且吲哚胺2,3-双加氧酶（IDO）刺激产生的神经活性色氨酸分解代谢产物（TRYCATs）增加，包括犬尿氨酸（KYN）。TRYCAT途径与长期新冠的身心症状和情感症状之间的关联尚未得到广泛研究。在本研究中，我们测量了90例长期新冠患者在急性感染缓解后3至10个月的血清TRY、TRYCATs、胰岛素抵抗（使用稳态模型评估指数2-胰岛素抵抗，HOMA2-IR）、C反应蛋白（CRP）、身心症状、抑郁和焦虑症状。我们能够构建一个严重长期新冠的内表型类别（占患者的22%），其TRY和氧饱和度（SpO2，急性感染期间）极低，犬尿氨酸、KYN/TRY比值、CRP升高，且在所有症状领域的评分都非常高。可以从身心症状（包括慢性疲劳-纤维肌痛）、抑郁和焦虑症状中提取一个因素，表明所有领域都是共同的生理-情感表型的表现。三种长期新冠生物标志物（CRP、KYN/TRY和IR）解释了生理-情感表型中约40%的变异。后者和KYN/TRY比值由急性感染期间的最高体温（PBT）和降低的SpO2显著预测。可以从三个症状领域以及基于CRP、KYN/TRY和IR（长期新冠）以及PBT和SpO2（急性COVID-19）的综合指标中提取一个经过验证的潜在向量。总之，长期新冠的生理-情感表型是急性和长期新冠期间炎症反应的表现，血浆色氨酸降低和犬尿氨酸增加可能导致这些影响。
