Incidence, Risk Factors and Outcomes of Delayed-onset Cytomegalovirus Disease in a Large Retrospective Cohort of Lung Transplant Recipients

Abstract

Background Cytomegalovirus (CMV) replication and disease commonly occur in lung transplant recipients after stopping anti-CMV prophylaxis. The epidemiology of CMV disease is not well-studied given difficulties in assembling representative study populations with prolonged follow-up. We hypothesized that delayed-onset CMV disease (> 100 days post-transplant) occurs more commonly than early-onset CMV disease in lung transplant recipients, and is associated with an increased risk of death. Methods We assembled a large cohort of lung transplant recipients using 2004 to 2010 ICD-9-CM billing data from 3 Agency for Healthcare Research and Quality (AHRQ) State Inpatient Databases (SID), and identified demographics, comorbidities, CMV disease coded during hospital readmission and inpatient death. We used Cox proportional hazard multivariate analyses to assess for an independent association between delayed-onset CMV disease and death. Results In the cohort of 1,528 lung transplant recipients from 12 transplant centers, delayed-onset CMV disease occurred in 13.7% (n=210) and early-onset CMV disease occurred in 3.3% (n=51). Delayed-onset CMV pneumonitis was associated with inpatient death > 100 days post-transplant (aHR 1.6, 95% CI 1.1-2.5), after adjusting for transplant failure/rejection (aHR 2.5, 95% CI 1.5-4.1), bacterial pneumonia (aHR 2.8, 95% CI 2.0-3.9), viral pneumonia (aHR 1.5, 95% CI 1.1-2.1), fungal pneumonia (aHR 1.8, 95% CI 1.3-2.3), single lung transplant (aHR 1.3, 95% CI 1.0-1.7) and idiopathic pulmonary fibrosis (aHR 1.4, 95% CI 1.0-1.8). Conclusions Delayed-onset CMV disease occurred more commonly than early-onset CMV disease among lung transplant recipients. These results suggest that delayed-onset CMV pneumonitis was independently associated with an increased risk of death.

Impact of donor and recipient cytomegalovirus serology on long‐term survival of lung transplant recipients

“…First, we evaluated CMV infection but not the impact of CMV syndrome or CMV disease on mortality; we also did not quantify infection in our study. CMV disease has been associated with increased risk of mortality in lung transplantation . Additionally, in monitoring for CMV infection, not all patients are monitored with the same intensity, the method of detecting CMV infection changed over time and we did not have data regarding the compliance with and duration of antiviral therapy receipt in individual patients.…”

Respiratory Viral Infections in Solid Organ and Hematopoietic Stem Cell Transplantation

“…179 Delayed-onset CMV pneumonitis (>100 days posttransplant), donor with positive CMV serology, asymptomatic CMV infection, and CMV disease at any time have been associated with increased mortality in lung transplant recipients. [182][183][184] CMV in HSCT patients can also cause a wide array of clinical manifestations, with CMV pneumonia being the most serious, resulting in a mortality of approximately 30%. 185,186 CMV reactivation alone is associated with lower overall mortality following HSCT.…”

Clinical significance of post‐prophylaxis cytomegalovirus infection in lung transplant recipients

“…Cytomegalovirus (CMV) is the most important viral pathogen developing in SOT recipients . Overt CMV disease, and particularly CMV pneumonitis, has been associated with impaired allograft function and survival in lung transplantation, in particular before the era of universal antiviral prophylaxis . However, the clinical impact of CMV replication on allograft outcomes, in particular after the discontinuation of antiviral prophylaxis (ie, post‐prophylaxis CMV infection), has not been completely established …”