Cytomegalovirus Infections

Cytomegalovirus (CMV) is a double-stranded DNA virus that belongs to the family of and is also known as herpesvirus-5 (HHV-5). The CMV genome is the largest among human viruses, measuring approximately 230 kb and containing 200 genes that encode proteins.  Infection with CMV is common in both children and adults, with a worldwide seroprevalence ranging from 24% to 100%, which increases with age. Transmission of CMV occurs through the exchange of bodily fluids, eg, saliva, fomites, transfusion of blood products, and by fluids during sexual contact. CMV can also be transmitted via solid organ transplantation (SOT) and hematopoietic stem cell transplantation (HSCT). As with other herpesviruses, it establishes lifelong latency, remaining dormant in monocytes through specific mechanisms of transcriptional silencing. CMV is a globally widespread virus that becomes latent after primary infection and can become reactivated in the setting of severe immunosuppression. In immunocompetent patients, primary CMV typically causes asymptomatic disease or mild to moderate mononucleosis-like or flu-like syndromes, characterized by symptoms such as malaise, fever, lymphadenopathy, and arthralgia. Infection with CMV is a leading cause of morbidity in immunosuppressed individuals, e.g., due to HIV/AIDS, after receiving SOT and HSCT. In the latter population, CMV can cause severe organ damage and even cause rejection of the transplanted organ. Last but not least, mothers who become infected while they are pregnant may pass the virus to the embryo, and in some cases, this can cause congenital CMV.  CMV infection is defined by the detection of active CMV replication in tissue specimens, peripheral blood, or other body fluids, irrespective of clinical manifestations. CMV disease refers to the presence of CMV infection in conjunction with clinically attributable symptoms and signs. It is subclassified into CMV syndrome, characterized by non-specific constitutional symptoms, eg, fever, malaise, and lymphadenopathy, which are often accompanied by hematologic abnormalities such as leukopenia or thrombocytopenia, and tissue-invasive or end-organ CMV disease. CMV syndrome involves direct viral-mediated injury to specific organs, including, but not limited to, the gastrointestinal tract, lungs, hepatobiliary system, renal parenchyma, myocardium, pancreas, central nervous system, and retina. Primary, but mostly reactivated CMV can cause viremia, infecting various organs, including the eyes, stomach, esophagus, and colon, especially in patients with profound immunosuppression. CMV colitis and CMV esophagitis are the two most common gastrointestinal (GI) tract manifestations of CMV disease.   Prevention of CMV viremia and CMV end-organ disease is critical, particularly in immunosuppressed patients. This can be achieved through assessment of CMV serostatus in both donor and recipient, along with regular monitoring for the emergence of viremia via frequent CMV DNA quantification. In high-risk populations, prophylactic strategies may involve universal antiviral administration to all at-risk individuals, targeted prophylaxis for those at highest risk, or a pre-emptive approach. The pre-emptive strategy involves initiating antiviral therapy upon early detection of CMV DNAemia, before the onset of clinical disease.