Is Epstein-Barr Virus (EBV) related to Long COVID?

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Last updated: June 30, 2025 • View editorial policy

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From the Guidelines

There is a potential link between Epstein-Barr Virus (EBV) reactivation and Long COVID, suggesting that EBV may contribute to the development of persistent symptoms in some patients. According to a recent study published in Nature Reviews Microbiology 1, EBV reactivation is one of the several hypotheses suggested for the pathogenesis of Long COVID, alongside persisting reservoirs of SARS-CoV-2, immune dysregulation, and autoimmunity. The study highlights that Long COVID is associated with a range of symptoms, including fatigue, cognitive difficulties, and neurological symptoms, which could be related to EBV reactivation.

Some key points to consider:

  • EBV is a common herpesvirus that infects most people during their lifetime and remains dormant in the body after initial infection 1.
  • The stress of acute COVID-19 may trigger EBV reactivation in some individuals, potentially contributing to ongoing symptoms 1.
  • Some clinicians are beginning to test for EBV reactivation in Long COVID patients using blood tests that measure EBV viral capsid antigen (VCA) antibodies, early antigen (EA) antibodies, and EBV DNA levels 1.
  • If EBV reactivation is detected, antiviral medications like valacyclovir (typically 1 gram three times daily for several weeks) might be considered, though this approach remains experimental and is not yet part of standard treatment guidelines 1.

It is essential to note that the current evidence is based on small-scale pilot studies, and more research is needed to fully understand the relationship between EBV and Long COVID. However, considering the potential link between EBV reactivation and Long COVID, testing for EBV reactivation and considering antiviral treatment may be a viable option for some patients, particularly those with persistent symptoms and no other clear underlying cause.

From the Research

Relationship Between EBV and Long COVID

  • Epstein-Barr Virus (EBV) reactivation has been proposed as a potential contributor to long COVID, with studies suggesting a link between EBV reactivation and long COVID symptoms such as fatigue and neurocognitive dysfunction 2, 3.
  • Research has shown that EBV reactivation is more common in individuals with long COVID, with one study finding that 66.7% of long COVID subjects were positive for EBV reactivation compared to 10% of control subjects 3.
  • Another study found that COVID-19 patients experienced increased reactivation of EBV compared to COVID-negative patients, with 27.1% of EBV reactivations occurring in the COVID-positive group 4.

Mechanisms and Associations

  • The exact mechanisms by which EBV reactivation contributes to long COVID are unclear, but it is thought that EBV reactivation may trigger hyperinflammation and autoimmunity, leading to persistent symptoms 5, 6.
  • Studies have also found associations between EBV reactivation and other factors, such as corticosteroid use and underlying medical conditions, which may contribute to the development of long COVID 5.
  • The reactivation of other latent viruses, such as human herpesvirus 6 (HHV-6), has also been implicated in the development of long COVID, highlighting the potential for multiple viral factors to contribute to the disorder 6.

Clinical Implications

  • The findings of these studies suggest that EBV reactivation may be a significant contributor to long COVID, and that targeted treatments may be beneficial in reducing symptoms and improving outcomes 2, 5.
  • Further research is needed to fully understand the relationship between EBV reactivation and long COVID, and to develop effective diagnostic and treatment strategies for this complex disorder 6.

References

1
Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

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Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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