Interferon-γ production by CMV-specific CD8+ T lymphocytes provides protection against cytomegalovirus reactivation in critically ill patients.

Abstract

To evaluate the usefulness of the secretion of interferon-γ (IFNγ) by cytomegalovirus (CMV)-specific CD8+ T cells to determine the risk of CMV reactivation in critically ill non-immunosuppressed patients. Two-center prospective cohort study including critically ill non-immunosuppressed CMV-seropositive patients admitted between December 2012 and March 2013. The incidence of CMV reactivation by polymerase chain reaction (real-time PCR) in plasma was investigated. IFNγ secretion by CMV-specific CD8+ T lymphocytes was determined at the time of admission to the intensive care unit (ICU) by means of the QuantiFERON(®)-CMV (QF-CMV) test. Cox regression analyses were performed to investigate CMV reactivation risk factors. Fifty-three patients were included, of whom 13 (24.5%) presented CMV reactivation. Twenty-six patients (49.1%) were QF-CMV "reactive" (QF-CMV(R)). Of the 26 QF-CMV(R) patients, 11.5% (3/26) had CMV reactivation, whereas 37% (10/27) of QF-CMV "non reactive" patients (QF-CMV(NR)) presented reactivation (p = 0.03). By Cox regression, the presence of QF-CMV(R) at ICU admission (HR 0.09, 95% CI 0.02-0.44; p = 0.003) was associated with a decreased risk of CMV reactivation. The sensitivity, specificity, positive predictive value, and negative predictive value of QF-CMV were 77, 57, 37, and 88%, respectively. Eleven of the 53 patients (20.7%) died during the follow-up period. Mortality was more frequent in patients with CMV reactivation (6/13, 46.1 vs. 5/40, 12.5%; p = 0.015). In critically ill non-immunosuppressed patients, the presence of functional CMV-specific CD8+ T lymphocyte response at intensive care unit admission provides protection against CMV reactivation.