The association of cytomegalovirus infection and cytomegalovirus serostatus with invasive fungal infections in allogeneic haematopoietic stem cell transplant recipients: a systematic review and meta-analysis

Abstract

Background: In allogeneic haematopoietic stem cell transplant (allo-HSCT) recipients, the inter-relationship between post-transplant cytomegalovirus (CMV) and subsequent invasive fungal infections (IFIs) is conflicting and the association of CMV serostatus with IFIs has not been evaluated. Objectives: To determine the relationship between CMV infection/serostatus and IFIs in allo-HSCT populations. Data sources: A systematic literature search was conducted from existence until 11 July 2021 using Medline, Embase and ISI Web of Science databases. Study eligibility criteria: Cross-sectional, prospective cohort, retrospective cohort and case–control studies that reported allo-HSCT recipients with CMV and without CMV who developed or did not develop IFIs after CMV infection. Participants: Allo-HSCT recipients. Interventions: Not applicable. Methods: A systematic search, screening, data extracting and assessing study quality were independently conducted by two reviewers. The Newcastle–Ottawa scale was used to assess risk of bias. data were analysed using the pooled effect estimates of a random-effects model. Results: A total of 18 and 12 studies were included for systematic review and meta-analysis, respectively. Post-transplant CMV infection significantly increased the risk of IFIs with a pooled hazard ratio (pHR) of 2.58 (1.78, 3.74), I2 = 75%. Further subgroup analyses by timing of IFIs, CMV definitions, study continents, study design and adjustment of effect estimates showed that post-transplant CMV infection consistently increased the risk of subsequent IFIs. High-risk CMV serostatus (D–/R+) increased the risk of IFIs with a pooled odds ratio (OR) of 1.33 (1.04, 1.71), I2 = 0%, but low-risk CMV serostatus (D–/R–) decreased the risk of IFIs with a pOR of 0.69 (0.55, 0.87), I2 = 0%. Conclusions: Post-transplant CMV infection and high-risk CMV serostatus increased the risk of IFIs, but low-risk CMV serostatus decreased risk of IFIs among allo-HSCT recipients. Further studies are needed to identify at-risk allo-HSCT recipients as well as to focus on fungal diagnostics and prophylaxis to prevent this fungal-after-viral phenomenon.