Investigation of Long COVID Prevalence and Its Relationship to Epstein-Barr Virus Reactivation

Abstract

Coronavirus disease 2019 (COVID-19) patients sometimes experience long-term symptoms following resolution of acute disease, including fatigue, brain fog, and rashes. Collectively these have become known as long COVID. Our aim was to first determine long COVID prevalence in 185 randomly surveyed COVID-19 patients and, subsequently, to determine if there was an association between occurrence of long COVID symptoms and reactivation of Epstein–Barr virus (EBV) in 68 COVID-19 patients recruited from those surveyed. We found the prevalence of long COVID symptoms to be 30.3% (56/185), which included 4 initially asymptomatic COVID-19 patients who later developed long COVID symptoms. Next, we found that 66.7% (20/30) of long COVID subjects versus 10% (2/20) of control subjects in our primary study group were positive for EBV reactivation based on positive titers for EBV early antigen-diffuse (EA-D) IgG or EBV viral capsid antigen (VCA) IgM. The difference was significant (p < 0.001, Fisher’s exact test). A similar ratio was observed in a secondary group of 18 subjects 21–90 days after testing positive for COVID-19, indicating reactivation may occur soon after or concurrently with COVID-19 infection. These findings suggest that many long COVID symptoms may not be a direct result of the SARS-CoV-2 virus but may be the result of COVID-19 inflammation-induced EBV reactivation.

Long COVID: to investigate immunological mechanisms and sex/gender related aspects as fundamental steps for tailored therapy

“…Organ damage caused by an excessive inflammatory response activated by the virus, persistent reservoirs of SARS-CoV-2 in certain tissues that could trigger post-infection morbidity, re-activation of pathogens due to immune dysregulation, host microbiome alterations, clotting/coagulation issues and autoimmunity due to molecular mimicry between SARS-CoV-2 and self-proteins have been hypothesized to play a role [ 10 ]. Furthermore, it has also been suggested that Long COVID symptoms may not be a direct result of the SARS-CoV-2 infection but may be the consequence of COVID-19 inflammation-induced Epstein Bar virus reactivation [ 11 ]. The search for fine molecular mechanisms underlying Long COVID is also underway.…”

Varicella-zoster virus reactivation causing herpes zoster ophthalmicus (HZO) after SARS-CoV-2 vaccination – report of three cases

“…Other virus reactivations reported after SARS-Cov-2 vaccination including Epstein-Barr virus and we noted a personal case of reactivation of herpes uveitis [ 8 ]. It is not our competence to formulate hypotheses on the mechanisms of reactivation.…”

Stress-Induced Epstein-Barr Virus Reactivation

“…This group had tested positive for COVID at least 90 days prior to the study; in a group of participants who tested positive 21–90 days prior to the study, six of nine patients with long COVID symptoms tested positive for EBV reactivation, while only one of eleven did in the control group. While the EBV antibody EBV EA-D IgG was correlated with experiencing long COVID symptoms, neither EBV VCA IgG antibody nor EBNA-1 IgG antibody demonstrated the same association [ 164 ].…”