Reactivation of EBV is significantly related to the dysfunction of cellular immunity[8]. EBV is latent in near 90% of people, which is the highest rate of herpes virus[9]. Therefore, EBV viremia can also be considered as one of the measures of functional exhaustion of cellular immunity. SARS-CoV-2 virus infection can cause functional exhaustion of antiviral lymphocytes as well as the cytopathic effect[10], This study showed that EBV reactivation in many COVID-19 patients. Various treatments have been proposed for COVID-19, but there is no established treatment yet. In this regard, immune dysfunction is likely to have a profound effect on the patient's prognosis, and patients with EBV viremia need more careful observation and treatment.
The possibility that EBV is not simply an indicator of reduced immunity, but also a cause of worsening of immune function cannot be ruled out. During the reactivation of EBV, EBV can interfere with the activity of NK cells and helper T cells. EBV occurs B cell’s transformation[11], and produces proteins that primarily impair the production of interferons during the lysis phase[12]. With this mechanism, infection or reactivation of EBV can reduce defense to infection with other pathogens. However, the role of EBV has not been studied in COVID-19.
The real pathogenicity of the reactivated EBV is still being discussed. A study has reported that EBV DNA is detected in the low respiratory tract of patients with severe respiratory tract with no other pathogen detected[13]. However, it is difficult to conclude that EBV has a cytopathic effect in all cases where other pathogens have not been identified, because it is not easy to identify the pathogen of pneumonia in many cases. Still, some say reactivated EBV may be pathogenic as a result of immunocompromise, others claim it is just an indicator of severe illness[8].
CMV showed a lower incidence than EBV. This tended to be similar in previous studies of EBV and CMV viremia in severe patients[5]. CMV may be overlooked due to low incidence, but it needs to be noted because it can cause serious complications such as pneumonia, enteritis, and CNS infection[14]. In our study, 2 patients developed CMV viremia. One of them developed CMV pneumonia and esophagitis, and the patient eventually died. Considering the frequent use of steroids in severe patients with COVID-19, it is necessary to pay attention to the immunocompromised status. Invasive aspergillosis has attracted attention with relatively many reports[15]. In addition to aspergillosis, other opportunistic infections such as CMV need to be noted, but not yet. physicians need to be cautious about monitoring for opportunistic infections such as CMV.
This study has several limitations. First, it was a very small number of patients. Second, the incidence of EBV viremia may vary depending on the severity of the infection. Third, because it is a simple observational study, it was not possible to observe the prognosis of EBV viremia and the cellular immunity associated with EBV viremia. Further studies are needed for more patients and the mechanism of EBV viremia.
In conclusion, it was found in patients with EBV and CMV viremia COVID-19, suggesting an immunocompromised condition. Further studies are needed to determine the role of EBV and CMV viremia in COVID-19.