Background: Predicting which lung transplant recipients (LTR) will develop CMV infection remains challenging. We previously explored the Quantiferon®-CMV (QF-CMV) assay and found that R+ patients were mostly QF-CMV positive, with many developing CMV infection despite this result. The aim of this retrospective cohort study was to explore two biomarkers of global immunity, the absolute lymphocyte count (ALC) and the mitogen component of the QF-CMV assay, as predictors of CMV infection in R+ LTR.
Methods: R+ LTR who had QF-CMV testing performed at the time of prophylaxis discontinuation were included. Cox models were used to evaluate ALC and mitogen values as predictors of CMV infection >150 IU/mL in blood and/or bronchoalveolar lavage fluid (BAL), controlling for duration of antiviral prophylaxis as a time-varying covariate. Optimal cutoffs were calculated with receiver-operating characteristic curves.
Results: Our cohort included 204 LTR (122 D+/R+, 82 D-/R+). Median prophylaxis duration was 5.5 months (IQR 5.2-5.2). QF-CMV results were mostly positive (155, 91%) with 30 (15%) testing negative and 19 (9%%) indeterminate. CMV infection occurred in 111 (76%), including 42 (21%) in blood and 103 (50%) in BAL. Patients with a CMV seropositive donor (D+) were more likely to develop CMV infection (HR 2.24, 95% CI 1.48-3.39, p<0.001). Median ALC values amongst patients who did and did not subsequently develop CMV infection were 1.1 cells/μL (IQR 0.6-1.7) and 1.4 cells/μL (IQR 1.1-1.7) respectively (p=0.006). Mitogen values were lower in patients who had CMV infection (median 2.8 IU/mL, IQR 0.6-8.8 vs. 4.6 IU/mL, 0.6-8.8, p=0.13). After adjusting for serostatus and duration of antiviral prophylaxis, both ALC (HR 0.70 for every 1x10³ cells/μL increase, 95% CI 0.53-0.94, p=0.016) and mitogen value (HR 0.94 for every 1.0 IU/mL increase, 95% CI 0.89-1.00, p=0.03) were independently associated with CMV infection. Using the calculated optimal cutoffs, patients with an ALC ≤1.0 x 1000 cells/μL (adjusted HR 1.92, 95% CI 1.28-2.89, p=0.002) and a mitogen value ≤3.6 IU/mL (adjusted HR 1.57, 95% CI 1.05-2.37, p=0.03) were more likely to experience CMV infection.
Conclusion: Within R+ LTR, the ALC and the mitogen component of the QF-CMV assay were able to predict post-prophylaxis CMV infection. D+ patients were higher risk, and extending antiviral prophylaxis was protective. These values could be used to risk-stratify patients and inform decision making regarding duration of antiviral prophylaxis and frequency of virologic monitoring. Additional studies are needed to further explore the role of immune biomarkers in the prediction of CMV and other opportunistic infections in LTR.