• Sara Fernández, Pedro Castro, and Elie Azoulay.
• Medical Intensive Care Unit, Hospital Clinic of Barcelona, University of Barcelona, Barcelona, Spain. sfernanm@clinic.cat.
• Intensive Care Med. 2025 Jan 7.

PurposeAdvances in therapeutic care are leading to an increase in the number of patients living with overt immunosuppression. These patients are at risk of cytomegalovirus (CMV) infection and disease that can lead to or develop during ICU admission. This manuscript aims to describe the clinical presentation, risk factors, and management of CMV infection and disease in this patient population.MethodsWe conducted a literature search in PubMed up to April 2024, focusing on CMV infection and disease in patients with overt immunosuppression (hematopoietic stem cell and solid organ transplantation, solid or hematologic malignancies, HIV infection, immunosuppressive drugs, including corticosteroids, and primary immunodeficiencies) admitted to the intensive care unit (ICU). As there is limited ICU-specific data on CMV in immunosuppressed patients, many of the findings were extrapolated from the general literature.ResultsCMV infection and disease in immunocompromised critically ill patients is associated with increased mortality and presents significant management challenges. Clinical manifestations are diverse, shaped by the underlying immune deficiency and primary disease. Pneumonia and encephalitis are among the most severe CMV end-organ diseases. CMV infection may also increase the risk of secondary infections and induce life-threatening conditions, such as thrombotic microangiopathy. Importantly, CMV reactivation is not synonymous with CMV disease, and qPCR testing of body fluids cannot reliably differentiate between viral shedding and tissue-invasive infection, which requires histopathological confirmation. Ganciclovir is commonly the first-line anti-viral, though maribavir shows potential for patients unresponsive to other antivirals. Identifying patients who require prophylactic or preemptive antiviral therapy is essential.ConclusionsCMV infection and disease in critically ill immunocompromised patients pose a unique challenge for intensivists. The broad spectrum of clinical presentations and the difficulty in distinguishing CMV-related symptoms from other causes require a high level of clinical suspicion. Accurate interpretation of nucleic acid load levels and careful evaluation of CMV's pathogenic role when it is found are critical. Further studies focusing specifically on CMV infection and disease in critically ill immunocompromised patients are needed to optimize management strategies.© 2025. Springer-Verlag GmbH Germany, part of Springer Nature.

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