Another major unresolved issue is whether CMV infection is associated with overt disease or clinical manifestations directly attributable to this virus in critically ill patients. CMV infection in immunocompetent patients generally presents with mononucleosis-like symptoms including fever and malaise with liver enzyme abnormalities [60, 61] , which are typically benign. However, 31 to 42% of the hospitalized patients with CMV infection may have organ involvement [60, 62] and rarely life-threatening CMV infection has also been reported [63, 64] . In critically ill patients, 10% (2/20) of those with CMV infection eventually developed severe CMV disease (pneumonitis, neurologic disease) in one study [10] . CMV pneumonia has also been diagnosed in 29 to 50% of patients with ARDS or VAP [29] [30] [31] ; however, this does not necessarily mean that CMV is the cause of ARDS or VAP. Critical illness due to serious pulmonary disease may predispose these patients to CMV infection in the lungs. In a cohort study in the ICU, 17% of critically ill patients who experienced fever for three or more days had CMV infection [18] . Current guidelines for the evaluation of new fever in critically ill adult patients list transfusion-asso- ciated CMV mononucleosis as a cause of fever [65] . However, it remains to be determined whether and how often CMV produces febrile syndrome and whether coexistent infection with HHV-6 is a contributor to this entity as shown in the transplant setting [34, [36] [37] [38] [39] [40] .