Abstract
Background: 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.
Methods: 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.
Results: 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.
Conclusion: 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.
Keywords: COVID-19; EBV; HERV; HHV6A; ME/CFS; herpesvirus reactivation; latent virus; myalgic encephalomyelitis/chronic fatigue syndrome.
【저자키워드】 COVID-19, ME/CFS, EBV, HERV, latent virus, herpesvirus reactivation, HHV6A, myalgic encephalomyelitis/chronic fatigue syndrome., 【초록키워드】 IgG, viral infection, Saliva, fatigue, antibody, SARS-COV-2 infection, Antibody Response, Symptom, risk factor, virus, chronic disease, Anti-viral, immunoassay, Post-viral fatigue, Reactivation, Patient, CMV, plasma, mechanisms, multiplex, overlap, syndrome, cohorts, anti-viral antibody, HERV-K, retrovirus, HSV2, nuclear, oral mucosa, healthy donor, shown, analyzed, virus, significantly, elevated, majority, triggered, sustained, systemically, baseline, herpesvirus, 【제목키워드】 fatigue, Patient, syndrome, virus, unique,