Does post-transplant cytomegalovirus increase the risk of invasive aspergillosis in solid organ transplant recipients? A systematic review and meta-analysis

Abstract

Background: Cytomegalovirus (CMV) and invasive aspergillosis (IA) cause high morbid-ity and mortality in solid organ transplant (SOT) recipients. There are conflicting data with respect to the impact of CMV on IA development in SOT recipients. Methods: A literature search was con-ducted from existence through to 2 April 2021 using MEDLINE, Embase, and ISI Web of Science databases. This review contained observational studies including cross-sectional, prospective co-hort, retrospective cohort, and case-control studies that reported SOT recipients with post-trans-plant CMV (exposure) and without post-transplant CMV (non-exposure) who developed or did not develop subsequent IA. A random-effects model was used to calculate the pooled effect estimate. Results: A total of 16 studies were included for systematic review and meta-analysis. There were 5437 SOT patients included in the study, with 449 SOT recipients developing post-transplant IA. Post-transplant CMV significantly increased the risk of subsequent IA with pORs of 3.31 (2.34, 4.69), I2 = 30%. Subgroup analyses showed that CMV increased the risk of IA development regardless of the study period (before and after 2003), types of organ transplantation (intra-thoracic and intra-abdominal transplantation), and timing after transplant (early vs. late IA development). Further analyses by CMV definitions showed CMV disease/syndrome increased the risk of IA development, but asymptomatic CMV viremia/infection did not increase the risk of IA. Conclusions: Post-trans-plant CMV, particularly CMV disease/syndrome, significantly increased the risks of IA, which high-lights the importance of CMV prevention strategies in SOT recipients. Further studies are needed to understand the impact of programmatic fungal surveillance or antifungal prophylaxis to prevent this fungal-after-viral phenomenon.