Long COVID-19 symptoms likely caused by Epstein-Barr virus reactivation

Epstein-Barr virus (EBV) reactivation resulting from the inflammatory response to novel coronavirus (COVID-19) infection may be the cause of previously unexplained long COVID symptoms, such as fatigue, brain fog, and rashes, that occur in approximately 30 percent of patients after recovery from initial COVID-19 infection, according to new research published in the journal Pathogens.

For the study, the researchers surveyed 185 randomly selected patients recovered from COVID-19 and found that 30.3 percent had long term symptoms consistent with long COVID after initial recovery from SARS-CoV-2, the virus that causes COVID-19. This included several patients with initially asymptomatic COVID-19 cases who later went on to develop long COVID symptoms.

The researchers then found, in a subset of 68 COVID-19 patients randomly selected from those surveyed, that 66.7 percent of long COVID subjects versus 10 percent of controls were positive for EBV reactivation based on positive EBV early antigen-diffuse (EA-D) IgG or EBV viral capsid antigen (VCA) IgM titers.

"We found similar rates of EBV reactivation in those who had long COVID symptoms for months, as in those with long COVID symptoms that began just weeks after testing positive for COVID-19," said David Hurley, PhD, study co-author and a professor and molecular microbiologist at the University of Georgia. "This indicated to us that EBV reactivation likely occurs simultaneously or soon after COVID-19 infection."

The relationship between SARS-CoV-2 and EBV reactivation described in this study opens up new possibilities for long COVID diagnosis and treatment, the researchers said. Additionally, they said that it may be prudent to test patients newly positive for COVID-19 for evidence of EBV reactivation indicated by positive EBV EA-D IgG, EBV VCA IgM, or serum EBV DNA tests. If patients show signs of EBV reactivation, they can be treated early to reduce the intensity and duration of EBV replication, which may help inhibit the development of long COVID.

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