Immune Monitoring Using QuantiFERON®-CMV Assay in Congenital Cytomegalovirus Infection: Correlation With Clinical Presentation and CMV DNA Load

Background. Cytomegalovirus (CMV)-specific CD8 + T-cell responses can be detected early in fetal life, but their role in the manifestations of congenital CMV (cCMV) infection remains largely unknown. Methods. CMV-specific CD8 + T-cell responses were assessed in neonates with cCMV using QuantiFERON (R)-CMV assay, within day 14 of life (T-0) and during the second month of life (T-1). Detection and quantification of CMV DNA in whole blood and urine samples were performed at both time points. QuantiFERON (R)-CMV results were evaluated in relation to timing of maternal infection, clinical manifestations of cCMV and CMV DNA levels. Results. Thirty neonates were enrolled (10/30 [33%] symptomatic; 20/30 [67%] asymptomatic). At T-0 16/30 (53%) subjects had a reactive QuantiFERON (R)-CMV result and 16/16 (100%) were asymptomatic, whereas 14/30 (47%) had a nonreactive or indeterminate QuantiFERON (R)-CMV result and 4/14 (29%) were asymptomatic. At T-1, 17/29 (59%) subjects had a reactive QuantiFERON (R) CMV result, and 17/17 (100%) were asymptomatic, whereas 12/29 (41%) had a nonreactive or indeterminate result and 3/12 (25%) were asymptomatic. At both T-0 and T-1 reactive QuantiFERON (R)-CMV results correlated with lack of symptoms (P = .0001). At T-1 median CMV DNAemia was lower in subjects with reactive QuantiFERON (R)-CMV results as compared with subjects with nonreactive or indeterminate results (1.82 log IU/mL [1.82-2.89] vs 2.55 log IU/mL [1.82-4.42], P = .009). No correlation was found between QuantiFERON (R)-CMV results and gestational age at maternal infection nor with urine CMV DNA levels. Conclusions. A detectable CMV-specific CD8 + T-cell response, evaluated using the QuantiFERON (R)-CMV assay, correlates with the lack of CMV-related symptoms and the control of CMV DNAemia.