Association Between Cytomegalovirus Reactivation and Clinical Outcomes in Immunocompetent Critically Ill Patients: A Systematic Review and Meta-Analysis

Lachance, Philippe; Chen, Justin Z; Featherstone, Robin; Sligl, Wendy

doi:10.1093/ofid/ofx029

Cited by 50 publications

(50 citation statements)

References 44 publications

(131 reference statements)

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“…Our study showed that universal prophylaxis outperformed the preemptive approach in CMV disease. However, CMV viremia is frequently detected in patients with severe infections, and so one must be skeptical about making a diagnosis of CMV disease in a patient with non‐specific symptoms and CMV viremia. Rigorous screening for other infectious etiologies must gain more attention to avoid the misdiagnosis of CMV disease and unnecessary exposure of recipients to highly toxic substances such as ganciclovir.…”

Section: Discussionmentioning

confidence: 99%

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Comparison of universal prophylaxis and preemptive approach for cytomegalovirus associated outcome measures in renal transplant patients: A meta‐analysis of available data

Çaşkurlu

Karadağ

Arslan

et al. 2018

Transplant Infectious Dis

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Cytomegalovirus (CMV) is a ubiquitous latent human virus that often causes complications in renal transplantation recipients. Universal prophylaxis and preemptive therapy are alternative strategies to prevent CMV associated complications. This meta‐analysis aimed to assess available data comparing the effectiveness of prophylaxis and preemptive therapy for preventing adverse outcomes. We searched the PubMed, Ovid, Web of Science, Cochrane Library, and Open Grey databases using a combination of keywords. Random effects models along with the Paule‐Mandel estimator were used to synthesize pooled effect estimates. Eleven studies were eligible for the final analysis. Universal prophylaxis was better at preventing CMV disease than the preemptive approach (risk difference = −0.0459; confidence intervals = −0.0791, −0.0127; P‐value = 0.0067; number needed to treat [NNT] = 22 [1/0.0459]; high, 79 [1/0.0127] patients; low, 13 [1/0.0791] patients). Subgroup analysis revealed a more consistent effect among studies published after 2010, with negligible between‐study heterogeneity. The NNT for universal prophylaxis to prevent one excess CMV disease concerning preemptive therapy was 16 (1/0.0630) patients (high, 25 [1/0.0394]; low, 12 [1/0.0867] patients) in the subgroup of studies performed after 2010. We detected no significant difference between the two strategies regarding acute rejection and graft loss, with negligible variability due to heterogeneity between studies. Although universal prophylaxis performed better than the preemptive strategy for the prevention of CMV disease, the high NNT value may discourage the use of CMV prophylaxis. Since there were no differences between the strategies concerning acute rejection and graft loss, this study supports the use of the preemptive approach as an alternative to universal prophylaxis.

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Section: Discussionmentioning

confidence: 99%

“…Disorders inducing progenitor cells such as infections naturally promote the replication of CMV . The reactivation of CMV in critically ill patients is associated with adverse outcomes . However, it is unclear if CMV viremia is merely a marker of an unfavorable outcome or the cause of adverse outcomes …”

Section: Introductionmentioning

confidence: 99%

Comparison of universal prophylaxis and preemptive approach for cytomegalovirus associated outcome measures in renal transplant patients: A meta‐analysis of available data

Çaşkurlu

Karadağ

Arslan

et al. 2018

Transplant Infectious Dis

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“…In particular, patients with bacterial sepsis or pneumonia have been reported to have a higher likelihood of CMV viremia ( 28 , 33 , 36 ). The risk of CMV viremia is not clearly related to disease severity at the time of admission based on prognostic and organ dysfunction scores, and the onset of CMV viremia tends to precede or accompany clinical decline ( 37 , 38 ), which support the possibility that CMV causes, rather than merely being a marker of, worse ICU outcomes in adults ( 23 – 25 ).…”

Section: Systemic CMV Reactivation In Immunocompetent Critically Ill mentioning

confidence: 99%

“…There have been more than 30 studies of immunologically normal, critically ill adult patients demonstrating an association between systemic CMV reactivation and worse outcomes in intensive care units (ICUs), as summarized in recent reviews ( 22 – 25 ). In these studies, CMV reactivation was defined as the detection of CMV in blood samples or, when feasible, in bronchoalveolar lavage (BAL) fluid, using CMV DNA PCR, antigen immunocytochemistry, or growth in shell vial culture.…”

Section: Systemic CMV Reactivation In Immunocompetent Critically Ill mentioning

confidence: 99%

“…More recent findings also suggest that CMV might have pervasive negative impact on health through indirect effects on the immune system ( 19 – 21 ). In particular, CMV has increasingly been recognized as a potential cause of disease in immunologically normal adults with critical illness ( 22 – 25 ). However, despite the fact that young children generally control CMV infection poorly compared to adults, little is known about the role of CMV in immunocompetent critically ill pediatric patients.…”

Section: Introductionmentioning

confidence: 99%

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The Potential Harm of Cytomegalovirus Infection in Immunocompetent Critically Ill Children

et al. 2018

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Cytomegalovirus (CMV) is a ubiquitous infection that causes disease in congenitally infected children and immunocompromised patients. Although nearly all CMV infections remain latent and asymptomatic in immunologically normal individuals, numerous studies have found that systemic viral reactivation is common in immunocompetent critically ill adults, as measured by detection of CMV in the blood (viremia). Furthermore, CMV viremia is strongly correlated with adverse outcomes in the adult intensive care unit (ICU), including prolonged stay, duration of mechanical ventilation, and death. Increasing evidence, including from a randomized clinical trial of antiviral treatment, suggests that these effects of CMV may be causal. Therefore, interventions targeting CMV might improve outcomes in adult ICU patients. CMV may have an even greater impact on critically ill children, particularly in low and middle income countries (LMIC), where CMV is regularly acquired in early childhood, and where inpatient morbidity and mortality are inordinately high. However, to date, there are few data regarding the clinical relevance of CMV infection or viremia in immunocompetent critically ill children. We propose that CMV infection should be studied as a potential modifiable cause of disease in critically ill children, and that these studies be conducted in LMIC. Below, we briefly review the role of CMV in immunologically normal critically ill adults and children, outline age-dependent differences in CMV infection that may influence ICU outcomes, and describe an agenda for future research.

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Prognostic significance of plasma cytomegalovirus (CMV) DNA load in immunocompetent patients with CMV pneumonia: A retrospective cohort study

Aydın Güçlü,

Demirdöğen,

Kazak

et al. 2024

Journal of Medical Virology

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Cytomegalovirus (CMV) pneumonia, often presented as pneumonitis, is characterized by respiratory failure and large interstitial infiltrates visible on chest radiographs. This retrospective cohort study investigates the predictive significance of plasma CMV DNA load on the short‐ and long‐term mortality among immunocompetent patients diagnosed with CMV pneumonia. The study included 61 immunocompetent patients suspected of having CMV pneumonia, treated with intravenous ganciclovir after positive CMV DNA results from bronchoalveolar lavage or plasma. Our multivariate Cox regression analysis identified several independent predictors of mortality. Having idiopathic pulmonary fibrosis (IPF) significantly increased the risk of in‐hospital mortality (HR: 7.27, 95% CI: 1.62–32.52, p = 0.009), as did shorter durations of antiviral therapy (HR: 0.90, 95% CI: 0.84–0.97, p = 0.005) and higher CMV DNA levels (>3870 IU/mL; HR: 9.63, 95% CI: 2.32–39.98, p = 0.002). High CMV DNA levels (>5154 IU/mL) were also predictors of 30‐day mortality (HR: 9.39, 95% CI: 2.20–40.01, p = 0.002). For 1‐year mortality, the presence of IPF (HR: 2.96, 95% CI: 1.08–8.06, p = 0.034), hypersensitivity pneumonia (HP) (HR: 4.30, 95% CI: 1.57–11.78, p = 0.005), shorter duration of total antiviral therapy (HR: 0.95, 95% CI: 0.93–0.99, p = 0.010), and higher CMV DNA levels (>327 IU/mL) (HR: 3.36, 95% CI: 1.33–8.47, p = 0.010) were identified as independent determinants. The study reveals that IPF increases short and long‐term mortality risks, while HP increases long‐term mortality. Extended antiviral treatment duration results in a 10% reduction in in‐hospital mortality for each additional day of treatment. Furthermore, elevated viral loads are associated with higher mortality rates, highlighting the necessity for careful monitoring.

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Association Between Cytomegalovirus Reactivation and Clinical Outcomes in Immunocompetent Critically Ill Patients: A Systematic Review and Meta-Analysis

Cited by 50 publications

References 44 publications

Comparison of universal prophylaxis and preemptive approach for cytomegalovirus associated outcome measures in renal transplant patients: A meta‐analysis of available data

Comparison of universal prophylaxis and preemptive approach for cytomegalovirus associated outcome measures in renal transplant patients: A meta‐analysis of available data

The Potential Harm of Cytomegalovirus Infection in Immunocompetent Critically Ill Children

Prognostic significance of plasma cytomegalovirus (CMV) DNA load in immunocompetent patients with CMV pneumonia: A retrospective cohort study

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