Volume 82, August 2024, 154766Author links open overlay panel, , , , , , , , , AbstractBackground

Cytomegalovirus (CMV) infection is associated with poor outcome in ICU patients. However, data on immunocompromised patients are scarce. This study aims to describe characteristics and outcomes of critically ill hematological patients and CMV infection. CMV disease characteristics and relationship between CMV viral load, CMV disease, coinfections by other pathogens and outcomes are described.

Methods

Retrospective single center study (Jan 2010-Dec 2017). Adult patients, admitted to the ICU, having underlying hematological malignancy and CMV infection were included. Results are reported as median (interquartile) or n (%). Factors associated with hospital mortality or CMV disease were analysed using logistic regression.

Results

178 patients were included (median age 55y [42–64], 69.1% male). Hospital mortality was 53% (n = 95). Median viral load was 2.7 Log [2.3–3.5]. CMV disease occurred in 44 (24.7%) patients. Coinfections concerned 159 patients (89.3%). After adjustment for confounders, need for vasopressors (OR 2.53; 95%CI 1.11–5.97) and viral load (OR 1.88 per Log; 95%CI 1.29–2.85) were associated with hospital mortality. However, neither CMV disease nor treatment were associated with outcomes. Allogeneic stem cell transplantation (OR 2.55; 95%CI 1.05–6.16), mechanical ventilation (OR 4.11; OR 1.77–10.54) and viral load (OR 1.77 per Log; 95%CI 1.23–2.61) were independently associated with CMV disease. Coinfections were not associated with CMV disease or hospital mortality.

Conclusion

In critically-ill hematological patients, CMV viral load is independently associated with hospital mortality. Conversely, neither CMV disease nor treatment was associated with outcome suggesting viral load to be a surrogate for immune status rather than a cause of poor outcome.

Section snippetsList of Abbreviations

CMVcytomegalovirusHSCThematopoietic stem cell transplantICUintensive care unitCNILcommission nationale informatique et libertéPCRpolymerase chain reactionCNScentral nervous systemGvHDgraft versus host diseaseSOFASequential organ failure assessmentIQRinterquartile rangeARDSacute respiratory distress syndrome

Background

Cytomegalovirus (CMV) infection is an endemic infection which infects between 50 and 100% of adult patients. Primary CMV infection usually happens in childhood and is most often asymptomatic or responsible for benign manifestations. The virus then persists in a state of latency in different type of host cells and remains asymptomatic. Like other herpesviruses, CMV reactivations are possible and generally asymptomatic in immunocompetent hosts. In case of cellular immunosuppression, CMV disease,

Patients and methods

A retrospective single centre study was conducted in the medical ICU of Saint Louis Hospital, Université de Paris (Paris, France) between January 2010 and December 2017.

Every adult patients admitted in ICU with positive CMV viral load and underlying hematological malignancy were included. Stem-cell transplant recipients for reason other than malignant hematological disease (sickle cell disease or aplastic anaemia) were also included.

The database was approved by CNIL, the French Informatics and

Standard procedures in the participating centre

The participating centre admit annually around a thousand critically ill patients of whom 50 to 60% are immunocompromised. Among solid organ transplant recipients and hematological patients, systematic blood CMV PCR are performed twice a week during ICU stay. Tissue and other sample search for CMV by PCR or hybridization techniques are performed according to clinical presentation. In our institution, anti-herpes viridae prophylaxis is systematic in patients with acute leukemia, myeloma and

CMV infection

By convention, CMV infection is defined as virus detection, usually DNA or viral proteins, in any biological fluid or tissue specimen, with or without clinical manifestations. It may result from primary infection or recurrent infection, which is usually caused by reactivation of latent virus (CMV reactivation) or, more rarely, by reinfection with a different CMV strain (CMV reinfection) [7]. In this article, we use the term “CMV infection” indifferently, knowing that it mainly refers to CMV

Study population

A total of 178 patients had a positive CMV PCR in whole blood and/or another body fluid during their ICU stay and, therefore, were included in our study (Fig. 1). Their main characteristics are illustrated in Table 1. Median age was 55 years (range: 42 to 64 years) and 123 patients (69.1%) were of male gender. Most frequent underlying malignancies were mainly non-Hodgkin's lymphoma (n = 89; 50%), acute leukemia (n = 34; 19.1%) and myeloma (n = 16; 9.0%). Thirty-seven patients (20.8%) were

Discussion

This study specifically focuses on critically-ill immunocompromised patients with CMV infection. Our results suggest that viral load may be associated with hospital mortality in these patients, with a possible dose-response relationship. Up to one fourth of patients had possible or probable associated CMV disease and a single patient had a proven CMV disease. CMV disease was significantly associated with CMV viral load, HSCT and mechanical ventilation, the latter being a marker of severity.

Availability of data and material

The datasets used during the current study are available from the corresponding author on reasonable request.

Funding

None.

CRediT authorship contribution statement

A. Baber: Writing – review & editing, Writing – original draft, Validation, Investigation, Data curation, Conceptualization. L. Calvet: Writing – review & editing, Writing – original draft, Visualization, Validation, Methodology, Investigation, Data curation, Conceptualization. C. Vissac: Writing – review & editing, Validation, Investigation, Data curation. M. Salmona: Writing – review & editing, Validation, Investigation, Data curation. J. Legoff: Writing – review & editing, Validation,

Declaration of competing interest

M. Darmon report having received consulting fees from Sanofi and Gilead-Kite, research support from MSD, and speaker fees from MSD, Gilead-Kite and Astellas.

Elie Azoulay has received fees for lectures from Gilead, Pfizer, Baxter and Alexion. His research group has been supported by Ablynx, Ficher & Payckle, Jazz Pharma, and MSD.

The other authors declare having no conflict of interest related to this manuscript.

Acknowledgement

M. Darmon had access to full data and takes responsibility for the content of the manuscript, including the data and analysis.

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