Coinfection rates and clinical outcome data for cytomegalovirus and Epstein-Barr virus in post-transplant patients: A systematic review of the literature

Background In transplant recipients, cytomegalovirus (CMV) infection increases morbidity and mortality; furthermore, coinfection with other human herpesviruses like the Epstein-Barr virus (EBV) may complicate their management. This systematic literature review aimed to summarize rates of CMV-EBV coinfection and associated clinical outcomes among solid organ transplant (SOT) and hematopoietic stem cell transplant (HSCT) recipients. Methods An electronic literature search was performed using pre-specified search strategies (January 1, 2010-October 31, 2018) and following established/best practice methodology. Of 316 publications identified, 294 did not report CMV-EBV coinfection and were excluded. Studies meeting the inclusion criteria were further analyzed. Due to limited reporting/heterogeneity, data were not meta-analyzable. Results Nine studies (six SOT; three HSCT) reported CMV-EBV coinfection; rates of coinfection post transplantation varied between 2.6% and 32.7%. Two studies indicated CMV reactivation to be an independent variable associated with EBV reactivation. Among SOT studies, higher rates of graft dysfunction (47.4% vs 22.9%), rejection episodes (20.0% vs 8.9%), or acute rejection (50.0% vs 31.0%) were reported for patients with coinfection than without. In HSCT studies, patients with graft-vs-host disease were not reported separately for coinfection. Two studies described cases of post-transplant lymphoproliferative disorder (PTLD) in patients with CMV-EBV coinfection and reported rates of PTLD of 92% and 100%. Conclusion The CMV-EBV coinfection rate in HSCT and SOT recipients varied and was associated with increased graft rejection and PTLD compared with patients without coinfection. Further research may improve understanding of the burden of CMV-EBV coinfection among transplant recipients.