Epstein-Barr virus (EBV) reactivation in post COVID-19

Abstract

Objective: To determine if there is a link between prolonged COVID symptoms and the reactivation of EBV.

Methods: This study was an observational (case-control) analysis involving 140 patients who tested positive for COVID-19 and are experiencing persistent symptoms such as fatigue and post-exertional malaise. Additionally, a control group of 80 individuals, matched for age and gender, who have fully recovered from SARS-CoV-2 infection without these symptoms, was included. The research took place between December 2023 and March 2024 at Benha University Hospitals in Benha, Egypt. The reactivation of the Epstein-Barr virus (EBV) was identified by detecting EBV genetic material using TaqMan probes, along with at least one set of primers (BamHI and LMP2).

Results: Initial hospitalization during acute COVID-19 infection is significantly associated with post-COVID fatigue (p-value 0.007*). No significant associations were found for risk factors like diabetes and hypertension. EBV replication observed was due to EBV reactivation rather than primary infection. EBV-specific antibody titers EBNA-1 IgG (p-value 0.004*) and EA-D IgG (p-value 0.008*). 40/140 (28.6 %) patients with COVID-19 with persistent fatigue showed EBV reactivation in contrast to 9/80 (11.3 %) of controls (P-value 0.003*) using the same detection methods.

Conclusion: EBV reactivation plays a role in Long-COVID syndrome following COVID-19 infection supporting the usage of EBV inhibitors for long-term COVID-19 treatment.

Keywords: COVID-19; Epstein-Barr virus (EBV); Long-COVID; SARS-CoV-2; fatigue.