Division of Cell Biology, Department of Biomedical and Clinical Sciences, Linköping University, Linköping, Sweden.
Division of Family Medicine and Primary Care, Department of Neurobiology, Care Sciences and Society, Karolinska Institute, Stockholm, Sweden.
Front Immunol. 2022 Oct 20;13:949787. doi: 10.3389/fimmu.2022.949787. eCollection 2022.
Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a chronic disease considered to be triggered by viral infections in a majority of cases. Symptoms overlap largely with those of post-acute sequelae of COVID-19/long-COVID implying common pathogenetic mechanisms. SARS-CoV-2 infection is risk factor for sustained latent virus reactivation that may account for the symptoms of post-viral fatigue syndromes. The aim of this study was first to investigate whether patients with ME/CFS and healthy donors (HDs) differed in their antibody response to mild/asymptomatic SARS-CoV-2 infection. Secondly, to analyze whether COVID-19 imposes latent virus reactivation in the cohorts.
Anti-SARS-CoV-2 antibodies were analyzed in plasma and saliva from non-vaccinated ME/CFS (n=95) and HDs (n=110) using soluble multiplex immunoassay. Reactivation of human herpesviruses 1-6 (HSV1, HSV2, VZV, EBV, CMV, HHV6), and human endogenous retrovirus K (HERV-K) was detected by anti-viral antibody fingerprints in saliva.
At 3-6 months after mild/asymptomatic SARS-CoV-2 infection, virus-specific antibodies in saliva were substantially induced signifying a strong reactivation of latent viruses (EBV, HHV6 and HERV-K) in both cohorts. In patients with ME/CFS, antibody responses were significantly stronger, in particular EBV-encoded nuclear antigen-1 (EBNA1) IgG were elevated in patients with ME/CFS, but not in HDs. EBV-VCA IgG was also elevated at baseline prior to SARS-infection in patients compared to HDs.
Our results denote an altered and chronically aroused anti-viral profile against latent viruses in ME/CFS. SARS-CoV-2 infection even in its mild/asymptomatic form is a potent trigger for reactivation of latent herpesviruses (EBV, HHV6) and endogenous retroviruses (HERV-K), as detected by antibody fingerprints locally in the oral mucosa (saliva samples). This has not been shown before because the antibody elevation is not detected systemically in the circulation/plasma.
肌痛性脑脊髓炎/慢性疲劳综合征（ME/CFS）被认为是一种由大多数情况下的病毒感染引发的慢性疾病。症状与 COVID-19/长新冠的急性后遗症有很大重叠，这意味着存在共同的发病机制。SARS-CoV-2 感染是潜伏病毒持续再激活的危险因素，可能导致病毒性疲劳综合征的症状。本研究的目的首先是调查 ME/CFS 患者和健康供体（HDs）在对轻度/无症状 SARS-CoV-2 感染的抗体反应方面是否存在差异。其次，分析 COVID-19 是否会在队列中引起潜伏病毒再激活。
使用可溶性多重免疫分析检测未经疫苗接种的 ME/CFS（n=95）和 HDs（n=110）的血浆和唾液中的抗 SARS-CoV-2 抗体。通过唾液中的抗病毒抗体指纹分析检测人疱疹病毒 1-6（HSV1、HSV2、VZV、EBV、CMV、HHV6）和人类内源性逆转录病毒 K（HERV-K）的再激活。
在轻度/无症状 SARS-CoV-2 感染后 3-6 个月，唾液中的病毒特异性抗体明显增加，表明两种队列中的潜伏病毒（EBV、HHV6 和 HERV-K）均发生强烈再激活。在 ME/CFS 患者中，抗体反应明显更强，特别是 ME/CFS 患者的 EBV 核抗原-1（EBNA1）IgG 升高，但 HDs 中没有升高。与 HDs 相比，在 SARS 感染前的基线时，EBV-VCA IgG 也升高。
我们的结果表明，ME/CFS 中针对潜伏病毒的抗病毒谱发生了改变且持续被激活。即使是轻度/无症状的 SARS-CoV-2 感染也是潜伏疱疹病毒（EBV、HHV6）和内源性逆转录病毒（HERV-K）再激活的强大触发因素，这是通过口腔黏膜（唾液样本）局部的抗体指纹检测到的。这以前没有被证明过，因为在循环/血浆中没有检测到系统的抗体升高。
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