Global Immune Biomarkers and Donor Serostatus Can Predict Cytomegalovirus Infection Within Seropositive Lung Transplant Recipients

Background. Predicting which lung transplant recipients (LTR) will develop cytomegalovirus (CMV) infection remains challenging. The aim of this retrospective cohort study was to further explore the predictive utility of global immune biomarkers within recipient seropositive (R + ) LTRs, focusing on the mitogen component of the QuantiFERON (QF)-CMV assay and the absolute lymphocyte count (ALC). Methods. R + LTR with QF-CMV testing performed at 5 mo posttransplant were included. ALC and mitogen were evaluated as predictors of CMV infection (>150 IU/mL) in plasma and/or bronchoalveolar lavage fluid using Cox regression, controlling for antiviral prophylaxis. Optimal cutoffs were calculated with receiver-operating characteristic curves. Results. CMV infection occurred in 111 of 204 patients (54%) and was associated with donor seropositivity (80/111 [72%] versus 42/93 [45%], P < 0.001), lower ALC (median 1.1 versus 1.4 × 1000 cells/μL, P = 0.004), and lower mitogen (2.8 versus 4.6, P = 0.03) values. Adjusted for serostatus and prophylaxis, each unit decrease in ALC (hazard ratio, 1.56 per 1000 cells/μL; 95% confidence interval, 1.19-2.08; P = 0.002) and mitogen (hazard ratio, 1.09 per 1 IU/mL; 95% confidence interval, 1.03-1.14; P = 0.001) were independently associated with CMV. Combining these 2 biomarkers did not substantially improve model performance. Conclusions. In R + LTRs, donor serostatus, ALC values, and the mitogen component of the QF-CMV assay were able to predict postprophylaxis CMV infection. Combining serostatus with either biomarker alone improved predictions, but using both tests together did not increase predictive utility further. These values could be used to risk stratify patients and inform decision-making regarding the duration of antiviral prophylaxis and frequency of virologic monitoring.