Cytomegalovirus infection in non-immunocompromised critically ill patients: A management perspective

Table 2 Patient outcomes in studies in critically ill immunocompetent patients

Year of publication	Ref.	Study design	Patient population	Sample size	Prevalence of CMV (%)	Mortality rate (%) CMV positive vs negative	ICU stay	Ventilator duration	Other outcomes
1990	Domart et al[22]	Prospective, single center	Mediastinitis following cardiac surgery	115	25	55 vs 37 (P < 0.01)	69+/-36 vs 48+/-27 (P < 0.05)	ND
1996	Stéphan et al[16]	Prospectivecase series, single center	Medico-surgical patients on mechanical ventilation	23	ND	52	ND	ND
1996	Papazian et al[15]	Prospective single centre	Ventilator associated pneumonia	86	29	ND	ND	No difference (P > 0.05)	Severe hypoxemia CMV +/- (72 vs 95 mmHg, P < 0.05)
1998	Kutza et al[7]	Prospective longitudinal, singles centre	Septic shock	34	32.4	ND	ND	ND	CMV active had higher TNFα, IL1ß, ALT
2006	Cook et al[23]	Prospective, singles centre	SICU	20		65 vs 33 (P = 0.006)	83.5 vs 36 (P < 0.03)	ND	92 vs 25 (P < 0.004)
2011	Heininger et al[24]	Prospective, singles center	Medical ICU with SAPS II > 40	56		55 vs 36	30 vs 23 (P = 0.0375)	ND
2005	Jaber et al[14]	Retrospective matched case control study, single centre	Medico-surgical ICU patients	80		20 vs 11 (P = 0.02)	41 vs 31 (P = 0.04)	35 vs 24 (P = 0.03)	Bacteremia 15 vs 7 (P = 0.05)
2006	von Müller et al[11]	Prospective observational study, single centre	Septic shock	38	18.4	57 vs 38 (NS)	54 vs 19 (P = 0.0025)	42 vs 16 (P = 0.0025)
2008	Ziemann et al[25]	Retrospective study	Medical ICU	138	35	28.6 vs 10.9 (P = 0.048)	32.6 vs 22.1 (P < 0.001)
2008	Limaye et al[2]	Prospective, multicentre	Mixed ICU	120	33	ND
2009	Chiche et al[13]	Prospective study	Medical ICU on mechanical ventilator for > 2 d	242	16.1	54 vs 37 (P = 0.082)	32 vs 12 (P < 0.001)	27 vs 10 (P < 0.001)	Ventilator free days at 28 and 60, P < 0.001. Increased risk of bacteremia, P < 0.033, increased bacterial nosocomial pneumonia, P < 0.001
2010	Chilet et al[26]	Prospective observational, single center	Surgical and trauma ICU	53	39.7	61 vs 46 (P = 0.40)	37 vs 11 (P = 0.01)	ND	TNF alpha, P = 0.80. CMV specific T cell response CD8+, P = 0.05. CD4, P = 0.04
2011	Heininger et al[24]	Prospective observational study	Mixed ICU	86	40.6	37.1 vs 35.3, (P = 0.861)	30 vs 12 (P < 0.001)	22 vs 7.5 (P = 0.003)
2009	Chiche et al[13]	Prospective, observation	Medical ICU	51	18	40 vs 13.3 (P = 0.21)	28 vs 14 (P = 0.013)	24 vs 8 (P = 0.019)	Bacterial VAP 40 vs 26.6 (P = 0.70)
2012	Coisel et al[27]	Prospective study	Medical ICU	93	ND	55 vs 20 (P < 0.01)	25.5 vs 13 (P = 0.037)	Bacteremia (%) 19.5 vs 10 (P = 0.009)	VFD at 60 (d) median [IQR] 0 [0-25] vs 50 [11.5-58] (P = 0.001). Shock (%) 77 vs 30 (P = 0.001, acute renal failure (%) 50 vs 16 (P = 0.01)
2013	Clari et al[28]	Prospective observational, single center study	Surgical and trauma ICU	48	0.27	8 out of 17 (reactivation of CMV) vs 5 out of 14 (without CMV reactivation) (P = 0.523)
2016	Ong et al[10]	Prospective, multicenter	ARDS patients on mechanically ventilated beyond day 4	271	27	Death by day 90 46 vs 28 (P < 0.01)	16 vs 9 (P < 0.01)	15 vs 8 (P < 0.01)
2015	Frantzeskaki et al[9]	Prospective, observation, multicenter	Mixed ICU, Mechanical ventilated seropositive (anti CMV IgG) positive	80	14	18 vs 22 (P > 0.05), 28 D mortality rate	32 vs 21 (NS)	27.5 vs 18 (NS)	SOFA score higher with CMV reactivation (P < 0.006), 28 d survival no difference
2016	Osawa et al[12]	Prospective, multicentre	Septic patients with BSI	100	20	20 vs 15 (P = 0.585)	27 vs 20 (P = 0.07)		VFD 15 vs 25 (P = 0.05). ICU free days 7 vs 18 (P = 0.01)
2019	Hraiech et al[17]	Retrospective, observational, single center	ARDS on VV ECMO, assessed for HSV and CMV	123	21.9	52 vs 59 (P = 0.58)	ICU LOS 29 vs 16 P < 0.01. Hospital LOS 44 vs 24 (P < 0.01)	34 vs 17.5 (P < 0.01)	Duration of ECMO 15 vs 9 (P < 0.01)
2021	Zhang et al[29]	single-center, prospective observational study	Medical ICU patients on mechanical ventialtion	71	18.3	69.2 vs 19 (P < 0.01)	ICU LOS 27 vs 12 (P < 0.01)	25 vs 10 (P < 0.01)	Hospital expenses higher in patients with CMV reactivation (P < 0.02)
2009	Kalil et al[1]	Systematic review	Included patients in ICU, 9 prospective and 4 retrospective studies	1258	17	OR: 1.93 (1.29–2.88) (P = 0.01)	ND	ND	ND
2009	Osawa et al[21]	Systematic review	13 studies, 9 prospective, 4 retrospective	ND	0-33	CMV + 29 to 100 as compared with CMV – 11 to 74 (OR: 5.7)	33 to 69 d vs 22 to 48 d (P < 0.05)	21 to 39 d vs 13 to 24 d (P < 0.05)	75% vs 50% (P = 0.04)
2017	Lachance et al[18]	Systematic review and meta-analysis	22 studies, randomized trials, observational studies (either retrospective or prospective), or case-control studies	2199	9–71	CMV reactivation was associated with a 2.5-fold increase in ICU mortality with low heterogeneity (10 studies, n = 970 patients, OR = 2.55, 95%CI = 1.87–3.47; P < 0.001)	MD 6.60 d, 95%CI = 3.09–10.12; P = 0.0002, I2 = 79%	ICU LOS was higher in CMV positive n (9 studies, n = 973 patients, MD 8.18 d, 95%CI = 6.14–10.22; P < 0.001)	Increase in nosocomial infections (OR 2.37-3.2) P < 0.05. Most common infections being ventilator-acquired pneumonia, bacteremsia, and fungal infections
2018	Li et al[3]	SR and MA	18 studies, mixed population	2398	CMV infection 27; CMV reactivation 31	All cause mortality OR: 2.16 (1.7-2.74)	ICU LOS stay (MD: 12 d)	9 d

CMV: Cytomegalovirus; APACHE: Acute physiology and chronic health evaluation; SAPS: Simplified acute physiology score; SOFA: Sequential organ failure assessment; ICU: Intensive care unit; OR: Odd’s ratio; PCR: Polymerase chain reaction; CRP: C-reactive protein; ND: No data; TNF: Tumor necrosis factor; IL: Interleukin; SICU: Surgical intensive care unit; VAP: Ventilator associated pneumonia; VFD: Ventilator free days; VV ECMO: Veno-venous extracorporeal membrane oxygenation; HSV: Herpes simplex virus; LOS: Length of stay; SR: Systematic review; MA: Meta analysis; ARDS: acute respiratory distress syndrome; IgG: Immunoglobulin G; IQR: interquartile range; ALT: alanine aminotransferase; NS: Not significant.