Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress 2023 EHA Congress 2023 ASCO Annual Meeting
Clinical Collections
Advances in Alzheimer’s

Keynote webinar | Spotlight on sleep in brain health

LIVE: Thursday 2nd May 2024, 18:00-19:30 (CEST)

Quality sleep is essential for health. But what happens to our brains when sleep patterns are disturbed? Join our experts to explore the interplay between sleep disruption and neurological diseases, and the questions that you need to be asking your patients to help you prevent the harmful effects of sleep deprivation.
ADVANCED SEARCH
Log in
Top
BMC Infectious Diseases
Published in: BMC Infectious Diseases 1/2018

Open Access 01-12-2018 | Research article

Cytomegalovirus infection and outcome in immunocompetent patients in the intensive care unit: a systematic review and meta-analysis

Authors: Xi Li, Yongbo Huang, Zhiheng Xu, Rong Zhang, Xiaoqing Liu, Yimin Li, Pu Mao

Published in: BMC Infectious Diseases | Issue 1/2018

Login to get access

Abstract

Background

Cytomegalovirus (CMV) infection is common in immunocompetent patients in intensive care units (ICUs). However, whether CMV infection or CMV reactivation contributes to mortality of immunocompetent patients remains unclear.

Methods

A literature search was conducted for relevant studies published before May 30, 2016. Studies reporting on CMV infection in immunocompetent patients in ICUs and containing 2 × 2 tables on CMV results and all-cause mortality were included.

Results

Eighteen studies involving 2398 immunocompetent patients admitted to ICUs were included in the meta-analysis. The overall rate of CMV infection was 27% (95%CI 22–34%, I2 = 89%, n = 2398) and the CMV reactivation was 31% (95%CI 24–39%, I2 = 74%, n = 666). The odds ratio (OR) for all-cause mortality among patients with CMV infection, compared with those without infection, was 2.16 (95%CI 1.70–2.74, I2 = 10%, n = 2239). Moreover, upon exclusion of studies in which antiviral treatment was possibly or definitely provided to some patients, the association of mortality rate with CMV infection was also statistically significant (OR: 1.69, 95%CI 1.01–2.83, I2 = 37%, n = 912,). For CMV seropositive patients, the OR for mortality in patients with CMV reactivation as compared with patients without CMV reactivation was 1.72 (95%CI 1.04–2.85, I2 = 29%, n = 664). Patients with CMV infection required significantly longer mechanical ventilation (mean difference (MD): 9 days (95% CI 5–14, I2 = 81%, n = 875)) and longer duration of ICU stay (MD: 12 days (95% CI 7–17, I2 = 70%, n = 949)) than patients without CMV infection. When analysis was limited to detection in blood, CMV infection without antiviral drug treatment or reactivation was not significantly associated with higher mortality (OR: 1.69, 95%CI 0.81–3.54, I2 = 52%, n = 722; OR: 1.49, I2 = 63%, n = 469).

Conclusion

Critically ill patients without immunosuppression admitted to ICUs show a high rate of CMV infection. CMV infection during the natural unaltered course or reactivation in critically ill patients is associated with increased mortality, but have no effect on mortality when CMV in blood. More studies are needed to clarify the impact of CMV infection on clinical outcomes in those patients.
Appendix
Available only for authorised users
Literature
1.
2.
Stadler LP, Bernstein DI, Callahan ST, Ferreira J, Gorgone Simone GA, Edwards KM, Stanberry LR, Rosenthal SL. Seroprevalence of cytomegalovirus (CMV) and risk factors for infection in adolescent males. Clin Infect Dis. 2010;51(10):e76–81.CrossRefPubMedPubMedCentral
3.
Hyde TB, Schmid DS, Cannon MJ. Cytomegalovirus seroconversion rates and risk factors: implications for congenital CMV. Rev Med Virol. 2010;20(5):311–26.CrossRefPubMed
4.
Bate SL, Dollard SC, Cannon MJ. Cytomegalovirus seroprevalence in the United States: the national health and nutrition examination surveys, 1988-2004. Clin Infect Dis. 2010;50(11):1439–47.CrossRefPubMed
5.
Musiani M, Zerbini M, Zauli D, Cometti G, La Placa M. Impairment of cytomegalovirus and host balance in elderly subjects. J Clin Pathol. 1988;41(7):722–5.CrossRefPubMedPubMedCentral
6.
Jackson SE, Mason GM, Wills MR. Human cytomegalovirus immunity and immune evasion. Virus Res. 2011;157(2):151–60.CrossRefPubMed
7.
Owers DS, Webster AC, Strippoli GF, Kable K, Hodson EM. Pre-emptive treatment for cytomegalovirus viraemia to prevent cytomegalovirus disease in solid organ transplant recipients. Cochrane Database Syst Rev. 2013;2:CD005133.
8.
Atabani SF, Smith C, Atkinson C, Aldridge RW, Rodriguez-Peralvarez M, Rolando N, Harber M, Jones G, O'Riordan A, Burroughs AK, et al. Cytomegalovirus replication kinetics in solid organ transplant recipients managed by preemptive therapy. Am J Transplant. 2012;12(9):2457–64.CrossRefPubMedPubMedCentral
9.
Deayton JR, Sabin CA, Johnson MA, Emery VC, Wilson P, Griffiths PD. Importance of cytomegalovirus viraemia in risk of disease progression and death in HIV-infected patients receiving highly active antiretroviral therapy. Lancet. 2004;363(9427):2116–21.CrossRefPubMed
10.
Ong DS, Klein Klouwenberg PM, Verduyn Lunel FM, Spitoni C, Frencken JF, Dekker HA, Schultz MJ, Bonten MJ, Cremer OL. Cytomegalovirus seroprevalence as a risk factor for poor outcome in acute respiratory distress syndrome*. Crit Care Med. 2015;43(2):394–400.CrossRefPubMed
11.
Walton AH, Muenzer JT, Rasche D, Boomer JS, Sato B, Brownstein BH, Pachot A, Brooks TL, Deych E, Shannon WD, et al. Reactivation of multiple viruses in patients with sepsis. PLoS One. 2014;9(2):e98819.CrossRefPubMedPubMedCentral
12.
NM O, NM S, SM A-R, SA H, Aaa AA. The impact of cytomegalovirus infection on mechanically ventilated patients in the respiratory and geriatric intensive care units. Egypt J Chest Dis Tuberc. 2014;63:239–45.CrossRef
13.
Heininger A, Haeberle H, Fischer I, Beck R, Riessen R, Rohde F, Meisner C, Jahn G, Koenigsrainer A, Unertl K, et al. Cytomegalovirus reactivation and associated outcome of critically ill patients with severe sepsis. Crit Care. 2011;15(2):R77.CrossRefPubMedPubMedCentral
14.
Bordes J, Maslin J, Prunet B, d'Aranda E, Lacroix G, Goutorbe P, Dantzer E, Meaudre E. Cytomegalovirus infection in severe burn patients monitoring by real-time polymerase chain reaction: a prospective study. Burns. 2011;37(3):434–9.CrossRefPubMed
15.
Chilet M, Aguilar G, Benet I, Belda J, Tormo N, Carbonell JA, Clari MA, Costa E, Navarro D. Virological and immunological features of active cytomegalovirus infection in nonimmunosuppressed patients in a surgical and trauma intensive care unit. J Med Virol. 2010;82(8):1384–91.CrossRefPubMed
16.
Chiche L, Forel J, Roch A, Guervilly C, Pauly V, Allardet-Servent J, Gainnier M, Zandotti C, Papazian L. Active cytomegalovirus infection is common in mechanically ventilated medical intensive care unit patients. Crit Care Med. 2009;37(6):1850–7.CrossRefPubMed
17.
Ziemann M, Sedemund-Adib B, Reiland P, Schmucker P, Hennig H. Increased mortality in long-term intensive care patients with active cytomegalovirus infection. Crit Care Med. 2008;36(12):3145–50.CrossRefPubMed
18.
Limaye AP, Kirby KA, Rubenfeld GD, Leisenring WM, Bulger EM, Neff MJ, Gibran NS, Huang ML, Santo Hayes TK, Corey L, et al. Cytomegalovirus reactivation in critically ill immunocompetent patients. Jama. 2008;300(4):413–22.CrossRefPubMedPubMedCentral
19.
von Muller L, Klemm A, Weiss M, Schneider M, Suger-Wiedeck H, Durmus N, Hampl W, Mertens T. Active cytomegalovirus infection in patients with septic shock. Emerg Infect Dis. 2006;12(10):1517–22.CrossRefPubMedPubMedCentral
20.
Jaber S, Chanques G, Borry J, Souche B, Verdier R, Perrigault PF, Eledjam JJ. Cytomegalovirus infection in critically ill patients: associated factors and consequences. Chest. 2005;127(1):233–41.CrossRefPubMed
21.
Cook CH, Martin LC, Yenchar JK, Lahm MC, McGuinness B, Davies EA, Ferguson RM. Occult herpes family viral infections are endemic in critically ill surgical patients. Crit Care Med. 2003;31(7):1923–9.CrossRefPubMed
22.
Heininger A, Jahn G, Engel C, Notheisen T, Unertl K, Hamprecht K. Human cytomegalovirus infections in nonimmunosuppressed critically ill patients. Crit Care Med. 2001;29(3):541–7.CrossRefPubMed
23.
Kutza AS, Muhl E, Hackstein H, Kirchner H, Bein G. High incidence of active cytomegalovirus infection among septic patients. Clin Infect Dis. 1998;26:1076–82.CrossRefPubMed
24.
Cook C, Yenchar J, Kraner T, Davies E, Ferguson R. Occult herpes family viruses may increase mortality in critically ill surgical patients. Am J Surg. 1998;176(4):357–60.CrossRefPubMed
25.
Domart Y, Trouillet JL, Fagon JY, Chastre J, Brun-Vezinet F, Gibert C. Incidence and morbidity of cytomegaloviral infection in patients with mediastinitis following cardiac surgery. Chest. 1990;97(1):18–22.CrossRefPubMed
26.
27.
Kalil A. Cytomegalovirus and mortality in critical care patients: another piece of the puzzle. Crit Care Med. 2012;40:303–5.CrossRefPubMed
28.
29.
Kalil AC, Florescu DF. Prevalence and mortality associated with cytomegalovirus infection in nonimmunosuppressed patients in the intensive care unit. Crit Care Med. 2009;37(8):2350–8.CrossRefPubMed
30.
Stang A. Critical evaluation of the Newcastle-Ottawa scale for the assessment of the quality of nonrandomized studies in meta-analyses. Eur J Epidemiol. 2010;25(9):603–5.CrossRefPubMed
31.
32.
Frantzeskaki FG, Karampi ES, Kottaridi C, Alepaki M, Routsi C, Tzanela M, Vassiliadi DA, Douka E, Tsaousi S, Gennimata V, et al. Cytomegalovirus reactivation in a general, nonimmunosuppressed intensive care unit population: incidence, risk factors, associations with organ dysfunction, and inflammatory biomarkers. J Crit Care. 2015;30(2):276–81.CrossRefPubMed
33.
Ong DS, Spitoni C, Klein Klouwenberg PM, Verduyn Lunel FM, Frencken JF, Schultz MJ, van der Poll T, Kesecioglu J, Bonten MJ, Cremer OL. Cytomegalovirus reactivation and mortality in patients with acute respiratory distress syndrome. Intensive Care Med. 2016;42(3):333–41.CrossRefPubMed
34.
Hardie DR, Korsman SN, Hsiao NY. Cytomegalovirus load in whole blood is more reliable for predicting and assessing CMV disease than pp65 antigenaemia. J Virol Methods. 2013;193(1):166–8.CrossRefPubMed
35.
Razonable RR, Fanning C, Brown RA, Espy MJ, Rivero A, Wilson J, Kremers W, Smith TF, Paya CV. Selective reactivation of human herpesvirus 6 variant a occurs in critically ill immunocompetent hosts. J Infect Dis. 2002;185(1):110–3.CrossRefPubMed
36.
Desachy A, Ranger-Rogez S, Francois B, Venot C, Traccard I, Gastinne H, Denis F, Vignon P. Reactivation of human herpesvirus type 6 in multiple organ failure syndrome. Clin Infect Dis. 2001;32(2):197–203.CrossRefPubMed
37.
Stephan F, Meharzi D, Ricci S, Fajac A, Clergue F, Bernaudin JF. Evaluation by polymerase chain reaction of cytomegalovirus reactivation in intensive care patients under mechanical ventilation. Intensive Care Med. 1996;22(11):1244–9.CrossRefPubMed
38.
Ho M. Cytomegalovirus infection in patients with bacterial sepsis. Clin Infect Dis. 1998;26(5):1083–4.CrossRefPubMed
39.
Griffiths PD, Cope AV, Hassan-Walker AF, Emery VC. Diagnostic approaches to cytomegalovirus infection in bone marrow and organ transplantation. Transpl Infect Dis. 1999;1(3):179–86.CrossRefPubMed
40.
Yun Z, Lewensohn-Fuchs I, Ljungman P, Ringholm L, Jonsson J, Albert J. A real-time TaqMan PCR for routine quantitation of cytomegalovirus DNA in crude leukocyte lysates from stem cell transplant patients. J Virol Methods. 2003;110(1):73–9.CrossRefPubMed
41.
Sylwester AW, Mitchell BL, Edgar JB, Taormina C, Pelte C, Ruchti F, Sleath PR, Grabstein KH, Hosken NA, Kern F, et al. Broadly targeted human cytomegalovirus-specific CD4+ and CD8+ T cells dominate the memory compartments of exposed subjects. J Exp Med. 2005;202(5):673–85.CrossRefPubMedPubMedCentral
42.
Hotchkiss RS, Monneret G, Payen D. Sepsis-induced immunosuppression: from cellular dysfunctions to immunotherapy. Nat Rev Immunol. 2013;13(12):862–74.CrossRefPubMedPubMedCentral
43.
Cohen J, Vincent JL, Adhikari NK, Machado FR, Angus DC, Calandra T, Jaton K, Giulieri S, Delaloye J, Opal S, et al. Sepsis: a roadmap for future research. Lancet Infect Dis. 2015;15(5):581–614.CrossRefPubMed
44.
Howard RJ, Simmons RL. Acquired immunologic deficiencies after trauma and surgical procedures. Surg Gynecol Obstet. 1974;139(5):771–82.PubMed
45.
Gascon P, Zoumbos NC, Young NS. Immunologic abnormalities in patients receiving multiple blood transfusions. Ann Intern Med. 1984;100(2):173–7.CrossRefPubMed
46.
Tarnok A, Schneider P. Pediatric cardiac surgery with cardiopulmonary bypass: pathways contributing to transient systemic immune suppression. Shock. 2001;16(Suppl 1):24–32.CrossRefPubMed
47.
48.
Cook CH, Trgovcich J, Zimmerman PD, Zhang Y, Sedmak DD. Lipopolysaccharide, tumor necrosis factor alpha, or interleukin-1beta triggers reactivation of latent cytomegalovirus in immunocompetent mice. J Virol. 2006;80(18):9151–8.CrossRefPubMedPubMedCentral
49.
Lawlor G, Moss AC. Cytomegalovirus in inflammatory bowel disease: pathogen or innocent bystander? Inflamm Bowel Dis. 2010;16(9):1620–7.CrossRefPubMed
50.
Chanques G, Jaber S. Treating HSV and CMV reactivations in critically ill patients who are not immunocompromised: con. Intensive Care Med. 2014;40(12):1950–3.CrossRefPubMed
Metadata
Title
Cytomegalovirus infection and outcome in immunocompetent patients in the intensive care unit: a systematic review and meta-analysis
Authors
Xi Li
Yongbo Huang
Zhiheng Xu
Rong Zhang
Xiaoqing Liu
Yimin Li
Pu Mao
Publication date
01-12-2018
Publisher
BioMed Central
Published in
BMC Infectious Diseases / Issue 1/2018
Electronic ISSN: 1471-2334
DOI
https://doi.org/10.1186/s12879-018-3195-5

Other articles of this Issue 1/2018

BMC Infectious Diseases 1/2018 Go to the issue

Study protocol

Effectiveness of repellent delivered through village health volunteers on malaria incidence in villages in South-East Myanmar: a stepped-wedge cluster-randomised controlled trial protocol

Research article

Validation of blood culture gram staining for the detection of Staphylococcus aureus by the ‘oozing sign’ surrounding clustered gram-positive cocci: a prospective observational study

Research article

Landscape and rodent community composition are associated with risk of hemorrhagic fever with renal syndrome in two cities in China, 2006–2013

Research article

Clinical characteristics, organ failure, inflammatory markers and prediction of mortality in patients with community acquired bloodstream infection

Research article

Challenges of interpreting epidemiologic surveillance pertussis data with changing diagnostic and immunization practices: the case of the state of São Paulo, Brazil

Research article

Virologic suppression in response to antiretroviral therapy despite extensive resistance within HIV-1 reverse transcriptase after the first virologic failure

ACC 2024 Congress Coverage

Heart Failure Video

Year in Review: Heart failure and cardiomyopathies

Watch now

Watch this official video from ACC.24 to hear Dr. Biykem Bozkurt discuss last year's major advances in heart failure and cardiomyopathies.

Semaglutide benefits people with type 2 diabetes and obesity-related heart failure

16-04-2024 Type 2 Diabetes News

Incentivised to exercise

11-04-2024 Lifestyle Modifications News

New intervention for STEMI-related cardiogenic shock

10-04-2024 Myocardial Infarction News

» View more highlights on the ACC 2024 congress hub page

Image Credits