Al Masoodi Wasim Talib Mahdi, Radhi Sami Waheed, Abdalsada Habiba Khdair, Niu Mengqi, Al-Hakeim Hussein Kadhem, Maes Michael
Department of Chemistry, College of Science, University of Kufa, Najaf, Iraq.
Department of Chemistry, Faculty of Medicine, University of Al-Ameed, Karbala, Iraq.
PLoS One. 2025 Mar 6;20(3):e0316373. doi: 10.1371/journal.pone.0316373. eCollection 2025.
Patients with Long COVID (LC) often experience neuropsychiatric symptoms such as depression, anxiety, and chronic fatigue syndrome (CFS), collectively referred to as the physio-affective phenome of LC. Activated immune-inflammatory pathways and insulin resistance significantly contribute to the physio-affective phenome associated with LC.
In a cohort of 90 individuals, categorized into those with and without LC, we evaluated, 3-6 months following acute SARS-CoV-2 infection, the correlations between the Hamilton Depression (HAMD), Hamilton Anxiety (HAMA), and Fibro-Fatigue (FF) Rating Scale scores, and serum C-reactive protein (CRP), prostaglandin E2 (PGE2), galanin-galanin receptor 1 (GAL-GALR1) signaling, insulin resistance, insulin-like growth factor (IGF-1), plasminogen activator inhibitor-1 (PAI1), S100B and neuron-specific enolase (NSE).
HAMD, HAMA, FF scores, CRP, PGE2, GAL-GALR1 signaling, insulin resistance, PAI1, NSE, and S100B are all higher in people with LC compared to those without LC. The HAMD/HAMA/FF scores were significantly correlated with PGE, CRP, GAL, GALR1, insulin resistance, and PAI1 levels, and a composite score based on peak body temperature (PBT) - oxygen saturation (SpO2) (PBT/SpO2 index) during the acute infectious phase. A combination of biomarkers explained a large part of the variance in CFS and affective scores (33.6%-42.0%), with GAL-GALR1 signaling, PGE2, and CRP being the top 3 most important biomarkers. The inclusion of the PBT/SpO2 index increased the prediction (55.3%-67.1%). The PBT/SpO2 index predicted the increases in GAL-GALR1 signaling.
These results indicate that the CFS and affective symptoms that are linked to LC are the consequence of metabolic aberrations, activated immune-inflammatory pathways, and the severity of inflammation during the acute phase of SARS-CoV-2 infection.
长期新冠（LC）患者常出现神经精神症状，如抑郁、焦虑和慢性疲劳综合征（CFS），统称为LC的生理情感表型。激活的免疫炎症途径和胰岛素抵抗显著促成了与LC相关的生理情感表型。
在一个由90名个体组成的队列中，分为有LC和无LC两组，我们在急性SARS-CoV-2感染后3至6个月，评估了汉密尔顿抑郁量表（HAMD）、汉密尔顿焦虑量表（HAMA）和纤维肌痛-疲劳（FF）评定量表得分，与血清C反应蛋白（CRP）、前列腺素E2（PGE2）、甘丙肽-甘丙肽受体1（GAL-GALR1）信号传导、胰岛素抵抗、胰岛素样生长因子（IGF-1）、纤溶酶原激活物抑制剂-1（PAI1）、S100B和神经元特异性烯醇化酶（NSE）之间的相关性。
与无LC的人相比，LC患者的HAMD、HAMA、FF得分、CRP、PGE2、GAL-GALR1信号传导、胰岛素抵抗、PAI1、NSE和S100B均更高。HAMD/HAMA/FF得分与PGE、CRP、GAL、GALR1、胰岛素抵抗和PAI1水平，以及急性感染期基于最高体温（PBT）-血氧饱和度（SpO2）的综合评分（PBT/SpO2指数）显著相关。一组生物标志物解释了CFS和情感得分中很大一部分的方差（33.6%-42.0%），其中GAL-GALR1信号传导、PGE2和CRP是最重要的前3种生物标志物。纳入PBT/SpO2指数提高了预测能力（55.3%-67.1%）。PBT/SpO2指数预测了GAL-GALR信号传导的增加。
这些结果表明，与LC相关的CFS和情感症状是代谢异常、激活的免疫炎症途径以及SARS-CoV-2感染急性期炎症严重程度的结果。
