title: Interferon-γ production by CMV-specific CD8+ T lymphocytes provides protection against cytomegalovirus reactivation in critically ill patients.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  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.
  
  
  RESULTS
  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).
  
  
  CONCLUSIONS
  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.
authors.affiliation: Unit of Infecious Diseases, Department of Internal Medicine, Hospital General Universitario, Universidad de Castilla La Mancha, Ciudad Real, Spain.|Spanish Network for the Research in Infectious Diseases (REIPI RD12/0015), Madrid, Spain.
authors.forename: Juan José
authors.initials: JJ
authors.lastname: Castón
authors.affiliation: Spanish Network for the Research in Infectious Diseases (REIPI RD12/0015), Madrid, Spain. sacanti@hotmail.com.|Clinical Unit of Infectious Diseases, Instituto Maimónides de Investigación Biomédica de Córdoba (IMIBIC), Reina Sofía University Hospital, University of Cordoba, Avda, Menéndez Pidal s/n, 14004, Cordoba, Spain. sacanti@hotmail.com.
authors.forename: Sara
authors.initials: S
authors.lastname: Cantisán
authors.affiliation: Unit of Infecious Diseases, Department of Internal Medicine, Hospital General Universitario, Universidad de Castilla La Mancha, Ciudad Real, Spain.
authors.forename: Francisco
authors.initials: F
authors.lastname: González-Gasca
authors.affiliation: Clinical Unit of Infectious Diseases, Instituto Maimónides de Investigación Biomédica de Córdoba (IMIBIC), Reina Sofía University Hospital, University of Cordoba, Avda, Menéndez Pidal s/n, 14004, Cordoba, Spain.
authors.forename: Aurora
authors.initials: A
authors.lastname: Páez-Vega
authors.affiliation: Intensive Care Unit, Hospital General Universitario, Ciudad Real, Spain.
authors.forename: Hasania
authors.initials: H
authors.lastname: Abdel-Hadi
authors.affiliation: Service of Microbiology, Hospital General Universitario, Ciudad Real, Spain.
authors.forename: Soledad
authors.initials: S
authors.lastname: Illescas
authors.affiliation: Intensive Care Unit, Hospital Universitario Reina Sofía, Cordoba, Spain.
authors.forename: Gema
authors.initials: G
authors.lastname: Alonso
authors.affiliation: Spanish Network for the Research in Infectious Diseases (REIPI RD12/0015), Madrid, Spain.|Clinical Unit of Infectious Diseases, Instituto Maimónides de Investigación Biomédica de Córdoba (IMIBIC), Reina Sofía University Hospital, University of Cordoba, Avda, Menéndez Pidal s/n, 14004, Cordoba, Spain.
authors.forename: Julián
authors.initials: J
authors.lastname: Torre-Cisneros
mesh_terms: D000328:Adult; D000368:Aged; D000998:Antiviral Agents / Q000627:therapeutic use; D015415:Biomarkers / Q000097:blood; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D018890:Chemoprevention / Q000379:methods / Q000592:standards; D016638:Critical Illness; D003587:Cytomegalovirus / Q000276:immunology* / Q000302:isolation & purification; D003586:Cytomegalovirus Infections / Q000453:epidemiology / Q000276:immunology* / Q000517:prevention & control; D005260:Female; D006801:Humans; D007121:Immunocompetence / Q000502:physiology; D007362:Intensive Care Units / Q000706:statistics & numerical data; D007371:Interferon-gamma / Q000097:blood / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D015337:Multicenter Studies as Topic; D016016:Proportional Hazards Models; D011446:Prospective Studies; D065840:Protective Factors; D060888:Real-Time Polymerase Chain Reaction; D012121:Respiration, Artificial / Q000009:adverse effects; D018570:Risk Assessment / Q000379:methods; D016036:Seroepidemiologic Studies; D013030:Spain / Q000453:epidemiology; D018709:Statistics, Nonparametric
chemical_list: D000998:Antiviral Agents; D015415:Biomarkers; D007371:Interferon-gamma
keywords: Critical care; Cytomegalovirus; Interferon-γ; Mechanical ventilation; Mortality; Replication