Saliva antibody-fingerprint of reactivated latent viruses after mild/asymptomatic COVID-19 is unique in patients with myalgic-encephalomyelitis/chronic fatigue syndrome

Abstract

BackgroundMyalgic 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.MethodsAnti-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.ResultsAt 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.ConclusionOur 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.

COVID-19 as a polymorphic inflammatory spectrum of diseases: a review with focus on the brain

“…Autoimmune reactions in adult patients and allergic reactions in children appear to be critical factors (Ortona & Malorni, 2022; Osmanov et al ., 2022). Reactivated latent viruses (which may affect long COVID symptoms) may also appear after mild asymptomatic COVID-19 (Apostolou et al ., 2022). Historically, immune genes protective against the bubonic plague, especially in Northern European populations, are associated with increased susceptibility to autoimmune diseases (Klunk et al ., 2022).…”

Long COVID: a review and proposed visualization of the complexity of long COVID

“…At 3-6 months after infection, virus-specific antibodies in saliva were substantially induced, indicating a strong reactivation of all three viruses in both cohorts. In patients with ME/CFS, however, antibody responses were significantly stronger, in particular against EBV-encoded nuclear antigen-1 (EBNA1) than in the controls ( 101 ).…”

What Role Does Microthrombosis Play in Long COVID?

“…Although this reflects a reasonable explanation, the presence of persistent latent or asymptomatic virus infection and the rise of antibodies should be proven more robustly. 77 Other than the above, Finlay et al 78 reported that infiltration of T cells expressing interferon-γ to the olfactory epithelium could be the cause of long-term smell loss after COVID-19 infection. They examined 24 olfactory epithelial biopsy specimens in PASC patients and found T cell-mediated inflammatory signaling was accompanied by a reduced number of olfactory sensory neurons.…”