6 型疱疹病毒的再活化和 IgA/IgM 介导的对激活素-A 的反应是长程 COVID（包括情感症状和慢性疲劳综合征）的基础

IF 3.8 4区医学 Q1 Medicine

Acta Neuropsychiatrica Pub Date : 2024-04-04 DOI:10.1017/neu.2024.10

Aristo Vojdani, Abbas F. Almulla, Bo Zhou, Hussein K. Al-Hakeim, Michael Maes

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引用次数: 0

摘要

背景：严重急性呼吸系统综合征冠状病毒 2（SARS-CoV-2）的持续感染、休眠病毒的再活化以及免疫氧化反应参与了长 COVID 的形成。研究目的研究长期COVID以及抑郁、焦虑和慢性疲劳综合征（CFS）症状是否与SARS-CoV-2、人类疱疹病毒6型（HHV-6）、Epstein-Barr病毒（EBV）的IgA/IgM/IgG以及免疫氧化生物标志物有关。研究方法我们对 90 名长期 COVID 患者和 90 名健康对照者进行了检查。我们测定了血清中针对 HHV-6 和 EBV 及其脱氧尿苷 5′-三磷酸核苷酸水解酶（duTPase）、SARS-CoV-2、活化素-A、C 反应蛋白（CRP）、高级氧化蛋白产物（AOPP）和胰岛素抵抗（HOMA2-IR）的 IgA/IgM/IgG。结果显示长COVID患者的IgG/IgM-SARS-CoV-2、IgG/IgM-HHV-6和HHV-6-duTPase、IgA/IgM-activin-A、CRP、AOPP和HOMA2-IR均明显升高。神经网络分析结果表明，长 COVID 诊断的预测准确率高达 80.6%（灵敏度：78.9%，特异性：81.8%，ROC 曲线下面积 = 0.876）；最主要的预测因子如下：IGA-活化素-A、IgG-HHV-6、IgM-HHV-6-duTPase、IgG-SARS-CoV-2 和 IgM-HHV-6（均为阳性），以及从所有病毒抗原的所有 IgA 水平中提取的一个因子（为阴性）。长 COVID 引起的情感症状的前 5 个预测因子是 IgM-HHV-6-duTPase、IgG-HHV-6、CRP、教育程度、IgA-活化素-A（预测准确率为 r = 0.636）。长 COVID 导致的 CFS 的前 5 个预测因子从高到低依次为CRP、IgG-HHV-6-duTPase、IgM-活化素-A、IgM-SARS-CoV-2 和 IgA-活化素-A（预测准确性：r = 0.709）。结论HHV-6的再激活、SARS-CoV-2的持续存在、对激活素-A的自身免疫反应以及激活的免疫氧化途径在长COVID的病理生理学及其情感症状和CFS的严重程度中起着重要作用。

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Reactivation of herpesvirus type 6 and IgA/IgM-mediated responses to activin-A underpin long COVID, including affective symptoms and chronic fatigue syndrome

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. Objectives: 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). Conclusion: 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.

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来源期刊

Acta Neuropsychiatrica 医学-精神病学

CiteScore

8.50

自引率

5.30%

发文量

审稿时长

6-12 weeks

期刊介绍： Acta Neuropsychiatrica is an international journal focussing on translational neuropsychiatry. It publishes high-quality original research papers and reviews. The Journal''s scope specifically highlights the pathway from discovery to clinical applications, healthcare and global health that can be viewed broadly as the spectrum of work that marks the pathway from discovery to global health.