Background
Coronavirus disease 2019 (COVID-19) can reactivate several latent viruses. Epstein–Barr virus (EBV) is a latent virus that is frequently reactivated in patients with critical illnesses. Recently, a high incidence of viremia has been reported in patients with severe COVID-19. However, it is unclear whether EBV viremia is the result of the severity of COVID-19 or if it affects the severity of COVID-19. Therefore, we conducted a cohort study to evaluate the effects of EBV on the progression of COVID-19.

Methods
We compared the incidence of EBV viremia between the COVID-19 and non-COVID-19 groups. Simplified Acute Physiology Score (SAPS) II and lymphocyte subsets were analyzed in patients with COVID-19. We also observed that patients with COVID-19 with EBV viremia progressed to severe pneumonia more often than those without EBV viremia.

Results
Two hundred and nine patients with COVID-19 were compared with the control (non-COVID-19) group. The incidence of EBV viremia was lower in the COVID-19 group than in the non-COVID-19 group (17.1% vs. 26.8%, P=0.034). In the subgroup analysis of the COVID-19 group, the EBV-positive group patients had more severe COVID-19 infection than the EBV-negative group (SAPS II, 22.3 vs. 17.4%; P=0.002). However, progression to moderate or severe pneumonia in patients with mild COVID-19 was rather high in the EBV-negative group (not statistically significant), contrary to our expectations.

Conclusions
Although the severity of COVID-19 may affect EBV viremia, there is no evidence that EBV viremia is a factor that exacerbates pneumonia in patients with early COVID-19. The effect of EBV viremia on prolonged organizing pneumonia should be further studied.