EBV Reactivation in Transplant Recipients following SARS-CoV-2 Infection: A Retrospective Study

Abstract

Reactivation and primary infection with a high Epstein Barr Virus (EBV) DNA level in kidney transplant patients could cause severe complications, including the development of Post-Transplantation Lymphoproliferative Disease (PTLD). While in the general population the reactivation of EBV after SARS-CoV-2 infection has been reported, very few data are available in transplant recipients. Our retrospective study aimed to evaluate a possible EBV reactivation in kidney transplant patients following SARS-CoV-2 infection and a possible impairment of the immune system. In addition, the effects of changes in immunosuppressive therapy on EBV DNA reactivation and vaccination were also evaluated. A total of 166 kidney transplant patients followed at the Kidney–Pancreas Transplant Ambulatory Nephrology Unit at Padova University Hospital were retrospectively considered for an observation period of 6 months from January 2020 to April 2023. EBV DNA level was measured by Rt-PCR and evaluated 6 months before and after SARS-CoV-2 infection. Patients’ serological states were established via quantification of anti-VCA and anti-EBNA (chemiluminescence). Patients’ immune systems were characterized by CD4+/CD8+ lymphocyte ratio (flow cytometry). EBV DNA was reactivated in 50% of the 166 patients with COVID-19 who completed the study. Older patients with more severe forms of COVID-19 had higher EBV reactivation (p < 0.05). EBV reactivation significantly increased in patients with severe SARS-CoV-2 infection requiring hospitalization compared to patients managed at home (p < 0.001). CD4+/CD8+ lymphocyte ratio was reduced in patients with a younger age of transplant (p < 0.01) and on a higher dose of steroids (p < 0.01). The results of our study confirm the role of immunodepression, especially in recent transplant patients and those on high steroids, in EBV reactivation. These results combined with the few available in the literature might contribute to providing an optimal management of immunosuppressive treatment for these patients in order to obtain an immune state unfavorable to the activation of latent viruses, including EBV.

Immunomodulatory Effect of COVID-19 on HLA-Antibody Profile in Renal Transplant Recipients

“…Two positive predictors of de novo DSA development, namely, graft biopsy (performed in patients with a worsening renal function) and the reactivation of EBV after SARS-CoV-2 infection, suggest an immunomodulatory effect of the SARS-CoV-2 virus. COVID-19 infection can lead to the reactivation of latent viruses such as EBV through an impairment of the immune system and lymphopenia [28]. Co-infection with Epstein-Barr virus (EBV) has been associated with severe clinical cases of COVID-19 infection as well as symptoms of long COVID [28,29].…”

“…COVID-19 infection can lead to the reactivation of latent viruses such as EBV through an impairment of the immune system and lymphopenia [28]. Co-infection with Epstein-Barr virus (EBV) has been associated with severe clinical cases of COVID-19 infection as well as symptoms of long COVID [28,29]. Stefanelli et al [28] analyzed EBV DNA six months before and after SARS-CoV-2 infection.…”

“…Co-infection with Epstein-Barr virus (EBV) has been associated with severe clinical cases of COVID-19 infection as well as symptoms of long COVID [28,29]. Stefanelli et al [28] analyzed EBV DNA six months before and after SARS-CoV-2 infection. Of the 166 patients with COVID-19 who completed the study, 50% showed the reactivation of EBV DNA.…”