Abstract：
BACKGROUND: Persistent infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), reactivation of dormant viruses, and immune-oxidative responses are involved in long COVID.
OBJECTIVE: To investigate whether long COVID and depressive, anxiety, and chronic fatigue syndrome (CFS) symptoms are associated with IgA/IgM/IgG to SARS-CoV-2, human herpesvirus type 6 (HHV-6), Epstein-Barr Virus (EBV), and immune-oxidative biomarkers.
METHODS: We examined 90 long COVID patients and ninety healthy controls. We measured serum IgA/IgM/IgG against HHV-6 and EBV and their deoxyuridine 5′-triphosphate nucleotidohydrolase (duTPase), SARS-CoV-2, and activin-A, C-reactive protein (CRP), advanced oxidation protein products (AOPP), and insulin resistance (HOMA2-IR).
RESULTS: Long COVID patients showed significant elevations in IgG/IgM-SARS-CoV-2, IgG/IgM-HHV-6, and HHV-6-duTPase, IgA/IgM-activin-A, CRP, AOPP, and HOMA2-IR. Neural network analysis yielded a highly significant predictive accuracy of 80.6% for the long COVID diagnosis (sensitivity: 78.9%, specificity: 81.8%, area under the ROC curve = 0.876); the topmost predictors were as follows: IGA-activin-A, IgG-HHV-6, IgM-HHV-6-duTPase, IgG-SARS-CoV-2, and IgM-HHV-6 (all positively) and a factor extracted from all IgA levels to all viral antigens (inversely). The top 5 predictors of affective symptoms due to long COVID were IgM-HHV-6-duTPase, IgG-HHV-6, CRP, education, IgA-activin-A (predictive accuracy of r = 0.636). The top 5 predictors of CFS due to long COVID were in descending order: CRP, IgG-HHV-6-duTPase, IgM-activin-A, IgM-SARS-CoV-2, and IgA-activin-A (predictive accuracy: r = 0.709).
CONCLUSIONS: Reactivation of HHV-6, SARS-CoV-2 persistence, and autoimmune reactions to activin-A combined with activated immune-oxidative pathways play a major role in the pathophysiology of long COVID as well as the severity of its affective symptoms and CFS.
OBJECTIVE: To investigate whether long COVID and depressive, anxiety, and chronic fatigue syndrome (CFS) symptoms are associated with IgA/IgM/IgG to SARS-CoV-2, human herpesvirus type 6 (HHV-6), Epstein-Barr Virus (EBV), and immune-oxidative biomarkers.
METHODS: We examined 90 long COVID patients and ninety healthy controls. We measured serum IgA/IgM/IgG against HHV-6 and EBV and their deoxyuridine 5′-triphosphate nucleotidohydrolase (duTPase), SARS-CoV-2, and activin-A, C-reactive protein (CRP), advanced oxidation protein products (AOPP), and insulin resistance (HOMA2-IR).
RESULTS: Long COVID patients showed significant elevations in IgG/IgM-SARS-CoV-2, IgG/IgM-HHV-6, and HHV-6-duTPase, IgA/IgM-activin-A, CRP, AOPP, and HOMA2-IR. Neural network analysis yielded a highly significant predictive accuracy of 80.6% for the long COVID diagnosis (sensitivity: 78.9%, specificity: 81.8%, area under the ROC curve = 0.876); the topmost predictors were as follows: IGA-activin-A, IgG-HHV-6, IgM-HHV-6-duTPase, IgG-SARS-CoV-2, and IgM-HHV-6 (all positively) and a factor extracted from all IgA levels to all viral antigens (inversely). The top 5 predictors of affective symptoms due to long COVID were IgM-HHV-6-duTPase, IgG-HHV-6, CRP, education, IgA-activin-A (predictive accuracy of r = 0.636). The top 5 predictors of CFS due to long COVID were in descending order: CRP, IgG-HHV-6-duTPase, IgM-activin-A, IgM-SARS-CoV-2, and IgA-activin-A (predictive accuracy: r = 0.709).
CONCLUSIONS: Reactivation of HHV-6, SARS-CoV-2 persistence, and autoimmune reactions to activin-A combined with activated immune-oxidative pathways play a major role in the pathophysiology of long COVID as well as the severity of its affective symptoms and CFS.
摘要：
背景：严重急性呼吸道综合征冠状病毒2（SARS-CoV-2）持续感染，重新激活休眠病毒，和免疫氧化反应参与长COVID。
目的：调查长期COVID和抑郁，焦虑,和慢性疲劳综合征（CFS）症状与IgA/IgM/IgG到SARS-CoV-2，人疱疹病毒6型（HHV-6），爱泼斯坦-巴尔病毒(EBV)和免疫氧化生物标志物。
方法：我们检查了90例长型COVID患者和90例健康对照。我们测量了针对HHV-6和EBV及其脱氧尿苷5'-三磷酸核苷酸水解酶（duTPase）的血清IgA/IgM/IgG，SARS-CoV-2和激活素A,C反应蛋白(CRP),高级氧化蛋白产品（AOPP），胰岛素抵抗（HOMA2-IR）。
结果：长型COVID患者IgG/IgM-SARS-CoV-2、IgG/IgM-HHV-6和HHV-6-duTPase显著升高，IgA/IgM-活化素-A，CRP,AOPP,HOMA2-IR神经网络分析对长期COVID诊断的预测准确率为80.6%(灵敏度：78.9%，特异性：81.8%，ROC曲线下面积=0.876)；最重要的预测因素如下：IGA-激活素-A，IgG-HHV-6,IgM-HHV-6-duTPase,IgG-SARS-CoV-2和IgM-HHV-6（均为阳性）以及从所有IgA水平提取到所有病毒抗原的因子（相反）。长期COVID引起的情感症状的前5位预测因子是IgM-HHV-6-duTPase，IgG-HHV-6,CRP,教育,IgA-激活素-A(预测准确度r=0.636)。长期COVID导致CFS的前5个预测因子依次为：CRP，IgG-HHV-6-duTPase，IgM-激活素-A,IgM-SARS-CoV-2和IgA-激活素-A(预测准确度:r=0.709)。
结论：HHV-6，SARS-CoV-2持久性的再激活，对活化素A的自身免疫反应与激活的免疫氧化途径相结合，在长型COVID的病理生理以及其情感症状和CFS的严重程度中起着重要作用。
目的：调查长期COVID和抑郁，焦虑,和慢性疲劳综合征（CFS）症状与IgA/IgM/IgG到SARS-CoV-2，人疱疹病毒6型（HHV-6），爱泼斯坦-巴尔病毒(EBV)和免疫氧化生物标志物。
方法：我们检查了90例长型COVID患者和90例健康对照。我们测量了针对HHV-6和EBV及其脱氧尿苷5'-三磷酸核苷酸水解酶（duTPase）的血清IgA/IgM/IgG，SARS-CoV-2和激活素A,C反应蛋白(CRP),高级氧化蛋白产品（AOPP），胰岛素抵抗（HOMA2-IR）。
结果：长型COVID患者IgG/IgM-SARS-CoV-2、IgG/IgM-HHV-6和HHV-6-duTPase显著升高，IgA/IgM-活化素-A，CRP,AOPP,HOMA2-IR神经网络分析对长期COVID诊断的预测准确率为80.6%(灵敏度：78.9%，特异性：81.8%，ROC曲线下面积=0.876)；最重要的预测因素如下：IGA-激活素-A，IgG-HHV-6,IgM-HHV-6-duTPase,IgG-SARS-CoV-2和IgM-HHV-6（均为阳性）以及从所有IgA水平提取到所有病毒抗原的因子（相反）。长期COVID引起的情感症状的前5位预测因子是IgM-HHV-6-duTPase，IgG-HHV-6,CRP,教育,IgA-激活素-A(预测准确度r=0.636)。长期COVID导致CFS的前5个预测因子依次为：CRP，IgG-HHV-6-duTPase，IgM-激活素-A,IgM-SARS-CoV-2和IgA-激活素-A(预测准确度:r=0.709)。
结论：HHV-6，SARS-CoV-2持久性的再激活，对活化素A的自身免疫反应与激活的免疫氧化途径相结合，在长型COVID的病理生理以及其情感症状和CFS的严重程度中起着重要作用。
