title: Cytomegalovirus reactivation in a general, nonimmunosuppressed intensive care unit population: incidence, risk factors, associations with organ dysfunction, and inflammatory biomarkers.
abstract: OBJECTIVE
  Cytomegalovirus (CMV) reactivation, a significant cause of morbidity and mortality in immunosuppression, may affect "immunocompetent" seropositive critically ill patients. The aim of this prospective, observational study was to define the incidence, risk factors, and the association with morbidity and mortality of CMV reactivation in a general population of critically ill immunocompetent patients. We also studied the relationship between reactivation and patients' inflammatory response, as expressed by cytokine levels and stress up-regulation by salivary cortisol.
  
  
  METHODS
  This study included mechanically ventilated CMV-seropositive patients. A quantitative real-time polymerase chain reaction (PCR) was performed for CMV plasma DNAemia determination, upon intensive care unit (ICU) admission and weekly thereafter until day 28. Cytomegalovirus reactivation was defined as CMV plasma DNAemia greater than or equal to 500 copies/mL. Upon ICU admission, interferon γ, interleukin (IL) 10, IL-17A, IL-2, IL-6, and tumor necrosis factor α were quantified in plasma, and morning saliva was obtained to measure cortisol. Disease severity was assessed by Acute Physiology and Chronic Health Evaluation II score, whereas the degree of organ dysfunction was quantified by Sequential Organ Failure Assessment score. Mortality, duration of mechanical ventilation, and ICU length of stay were recorded.
  
  
  RESULTS
  During the study period, 80 (51 men) patients with a median age of 63 years fulfilled the inclusion criteria. Reactivation of CMV occurred in 11 patients (13.75%). Median day of reactivation was day 7 post ICU admission. Total number of red blood cell units transfused (odds ratio [OR], 1.50; confidence interval [CI], 1.06-2.13; P = .02) and C-reactive protein levels upon ICU admission (OR, 1.01; CI, 1.00-1.02; P = .02) were independently associated with CMV reactivation. High IL-10 was marginally related to reactivation (P = .06). Sequential Organ Failure Assessment scores were higher in the group with CMV reactivation compared with patients without reactivation during the entire 28-day observation period (P < .006). Salivary cortisol, mortality, length of ICU stay, and duration of mechanical ventilation were similar in the 2 groups.
  
  
  CONCLUSIONS
  Cytomegalovirus reactivation occurred in 13.75% of critically ill, immunocompetent patients. The degree of inflammation and the total number of transfused red blood cells units constituted risk factors. Cytomegalovirus reactivation was associated with more severe of organ dysfunction, but not with a worse clinical outcome.
authors.affiliation: Second Department of Critical Care Medicine, University of Athens, Medical School, "Attikon" Hospital, Athens, Greece. Electronic address: ffrantzeska@gmail.com.
authors.forename: Frantzeska G
authors.initials: FG
authors.lastname: Frantzeskaki
authors.affiliation: Second Department of Critical Care Medicine, University of Athens, Medical School, "Attikon" Hospital, Athens, Greece.
authors.forename: Eirini-Sofia
authors.initials: ES
authors.lastname: Karampi
authors.affiliation: Department of Cytopathology, University of Athens, Medical School, "Attikon" Hospital, Athens, Greece.
authors.forename: Christina
authors.initials: C
authors.lastname: Kottaridi
authors.affiliation: Department of Cytopathology, University of Athens, Medical School, "Attikon" Hospital, Athens, Greece.
authors.forename: Maria
authors.initials: M
authors.lastname: Alepaki
authors.affiliation: First Department of Critical Care Medicine, University of Athens, Medical School, "Evangelismos" Hospital, Athens, Greece.
authors.forename: Christina
authors.initials: C
authors.lastname: Routsi
authors.affiliation: Endocrinology Department, "Evangelismos" Hospital, Athens, Greece.
authors.forename: Marinella
authors.initials: M
authors.lastname: Tzanela
authors.affiliation: Endocrine Unit, Second Department of Internal Medicine, University of Athens, Medical School, "Attikon" Hospital, Athens, Greece.
authors.forename: Dimitra Argyro
authors.initials: DA
authors.lastname: Vassiliadi
authors.affiliation: First Department of Critical Care Medicine, University of Athens, Medical School, "Evangelismos" Hospital, Athens, Greece.
authors.forename: Evangelia
authors.initials: E
authors.lastname: Douka
authors.affiliation: First Department of Critical Care Medicine, University of Athens, Medical School, "Evangelismos" Hospital, Athens, Greece.
authors.forename: Sofia
authors.initials: S
authors.lastname: Tsaousi
authors.affiliation: Department of Microbiology, University of Athens, Medical School, Athens, Greece.
authors.forename: Vasiliki
authors.initials: V
authors.lastname: Gennimata
authors.affiliation: Department of Endocrinology, "Elena" Hospital, Athens, Greece.
authors.forename: Ioannis
authors.initials: I
authors.lastname: Ilias
authors.affiliation: Second Department of Critical Care Medicine, University of Athens, Medical School, "Attikon" Hospital, Athens, Greece.
authors.forename: Nikitas
authors.initials: N
authors.lastname: Nikitas
authors.affiliation: Second Department of Critical Care Medicine, University of Athens, Medical School, "Attikon" Hospital, Athens, Greece.
authors.forename: Apostolos
authors.initials: A
authors.lastname: Armaganidis
authors.affiliation: Department of Cytopathology, University of Athens, Medical School, "Attikon" Hospital, Athens, Greece.
authors.forename: Petros
authors.initials: P
authors.lastname: Karakitsos
authors.affiliation: Third Department of Pediatrics, University of Athens, Medical School, "Attikon" Hospital, Athens, Greece.
authors.forename: Vassiliki
authors.initials: V
authors.lastname: Papaevangelou
authors.affiliation: Second Department of Critical Care Medicine, University of Athens, Medical School, "Attikon" Hospital, Athens, Greece.
authors.forename: Ioanna
authors.initials: I
authors.lastname: Dimopoulou
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015415:Biomarkers; D016638:Critical Illness; D016207:Cytokines / Q000276:immunology*; D003587:Cytomegalovirus / Q000235:genetics / Q000502:physiology*; D003586:Cytomegalovirus Infections / Q000453:epidemiology* / Q000276:immunology; D004279:DNA, Viral / Q000097:blood*; D005260:Female; D006801:Humans; D007121:Immunocompetence; D015994:Incidence; D007362:Intensive Care Units; D008297:Male; D008875:Middle Aged; D009102:Multiple Organ Failure / Q000453:epidemiology / Q000276:immunology; D063305:Organ Dysfunction Scores; D011446:Prospective Studies; D060888:Real-Time Polymerase Chain Reaction; D012121:Respiration, Artificial; D012307:Risk Factors; D012463:Saliva / Q000737:chemistry; D014775:Virus Activation; D055815:Young Adult; D015035:Zinc Oxide-Eugenol Cement / Q000032:analysis
chemical_list: D015415:Biomarkers; C495565:Cortisomol; D016207:Cytokines; D004279:DNA, Viral; D015035:Zinc Oxide-Eugenol Cement
keywords: Critical illness; Cytomegalovirus; Inflammatory biomarkers; Multiorgan dysfunction