Key Points:

  • The prevalence of persistent symptoms after the resolution of acute illness in COVID-19 is approximately 30%.
  • A variety of clinical manifestations have been associated with EBV reactivation, many of which have similarities with symptoms of long-COVID.
  • A recent retrospective study of patients with long-COVID found that 67.7% were positive for EBV reactivation compared to 10% of control subjects.
  • A portion of long-COVID symptoms may be the result of COVID-19 inflammation-induced EBV reactivation.

The prevalence of persistent symptoms after the resolution of acute illness in COVID-19 is approximately 30%. Known as long-COVID, these symptoms include fatigue, brain fog, sleep difficulties, arthralgia, pharyngitis, myalgia, headaches, fever, gastrointestinal upset, and skin rashes with a variety of presentations. Symptoms of long-COVID have also been observed in those with asymptomatic, mild and severe COVID-19.

Epstein–Barr virus (EBV) is a human gamma-herpesvirus. It is known to have infected and generally become latent in more than 90% of the global population, including more than 95% of healthy adults. When contracted in childhood, EBV is usually asymptomatic; however, if the primary infection occurs in adolescence or adulthood, it commonly results in an acute condition inducing massive lymphocytosis and can sometimes cause chronic infections or serially reactivated infections. 

A variety of clinical manifestations have been associated with Epstein-Barr Virus reactivation, including fatigue, psychoneurosis/brain fog, sleep disturbance, arthralgia, pharyngitis, myalgia, headaches, fever, gastrointestinal complaints, and various skin rashes. Many of these symptoms have similarities with symptoms of long-COVID.

A recent retrospective study aimed to determine if there was evidence of a relationship between the occurrence of long-COVID symptoms and Epstein-Barr Virus reactivation. The analysis of 185 COVID patients, in which 56 (30.3%) reported unabating long-COVID symptoms, found that 67.7% were positive for Epstein-Barr Virus reactivation compared to 10% of control subjects. The rate of EBV reactivation was the same in subjects whose symptoms persisted for longer than 90 days after initial infection and those whose symptoms persisted for 21-90 days after initial infection.

Symptoms of EBV reactivation such as skin lesions, tinnitus and hearing loss resembles the symptoms experienced by COVID-19 patients, such as COVID-toes and some neurological manifestations. EBV reactivation has been reported to play a role in the pathogenesis of myocarditis, inflammatory cardiomyopathy, and acute myocardial infarction. EBV is also associated with a number of lymphoid and epithelial tumours. While rare, given that EBV reactivation has been associated with many serious clinical manifestations, further studies would be prudent to determine if any of these become more frequent in COVID-19 patients.

Clinically, an awareness of the associations between SARS-CoV-2 and EBV reactivation creates new opportunities for long-COVID diagnosis, management, and possible treatments. EBV reactivation may occur soon after or concomitantly with COVID-19 infection, including after initially asymptomatic infections. The SARS-CoV-2 virus may stimulate sequalae involving other infectious agents that contribute to many long-COVID symptoms. Thus, it is worth considering that a portion of long-COVID symptoms may be the result of COVID-19 inflammation-induced EBV reactivation.

Naturopathically, therapies which target the immune dysfunction induced by EBV reactivation may offer a feasible therapeutic approach for this subset of patients.

Source:

Gold, J. E., Okyay, R. A., Licht, W. E., & Hurley, D. J. (2021). Investigation of Long-COVID Prevalence and Its Relationship to Epstein-Barr Virus Reactivation. Pathogens (Basel, Switzerland), 10(6), 763. https://doi.org/10.3390/pathogens10060763