ABSTRACT
There are several human herpesviruses. A common characteristic of infection by these viruses is latency, by which the virus assumes a non-replicative state, subverting the attentions of the host's immune response. In immunocompetent hosts, herpesviruses are immunologically controlled, although periodic virus shedding can occur. In situations where immunological control is lost, herpesviruses can reactivate and produce clinically apparent disease. It is now becoming apparent that COVID-19 or exposure to COVID-19 vaccines can exert several effects on the immune system. The pandemic of COVID-19 shows no sign of abating, with new severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) variants continuing to evolve. Several COVID-19 vaccines have been developed, and much of the world's population has either experienced COVID-19 or been vaccinated against it. There are an increasing number of reports of associations between herpesvirus infections or reactivations and COVID-19 or COVID-19 vaccination. For instance, a positive cytomegalovirus serostatus may indicate a greater likelihood of severe COVID-19, and herpes simplex virus reactivation may be linked to increased mortality. Epstein-Barr virus reactivation appears to be associated with post-acute sequelae of COVID-19. Finally, herpes zoster has been reported to be associated with COVID-19 vaccination. This brief narrative review will provide several insights into associations between herpesvirus infections or reactivations and COVID-19 or SARS-CoV-2 vaccination.
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.