A systematic literature review on the humanistic burden of cytomegalovirus

Figures & data

Figure 1. PRISMA flow diagram of screening process and study selection for humanistic burden of CMV infection.

Table 1. Characteristics of included studies reporting QoL, auditory performance, cognitive development and mental health outcomes related to CMV infection (n = 38).

Reference	Study design	Study period	Country	Study population^a	Subpopulations^b and sample size	Other study characteristic information
QoL (n = 5)
Korndewal et al.^32	Retrospective	2014	Netherlands	Children	Children with cCMV (n = 133); Children with cCMV and long-term impairment^b; Children with cCMV without long-term impairment^b; Children without cCMV (n = 274)^b; Children without cCMV with long-term impairment^b; Children without cCMV without long-term impairment^b	Impacts of cCMV on child development, QoL, and daily life were reported
Katusic et al.^33	Prospective	2021	United States	Adults	Asymptomatic cCMV (n = 61); Controls (n = 23); Asymptomatic cCMV with hearing loss (n = 14); Controls with hearing loss (n = 2); Asymptomatic cCMV without hearing loss (n = 47); Controls without hearing loss (n = 21)	QoL outcomes among adults identified at birth as having asymptomatic cCMV were compared with a control group using the self-reported QOLI
Smit et al.^34	Systematic literature review	2013	Belgium	General population	Women of childbearing age with CMV^b	DALYs as a measure of disease burden for toxoplasmosis and cCMV infections were calculated using data from a systematic review covering recent literature (1995-2015) on the seroprevalence and incidence of toxoplasmosis and CMV infections in women of reproductive age and the incidence of both congenital infections in Belgium
Albright et al.^35	Decision model	2018	United States	General population	Pregnant women	Health utility values were used to calculate QALY values for each maternal health state (miscarriage, termination, intrauterine fetal demise, neonatal death, care for neonate with severe disability from CMV, delivery and care of healthy child)
Strandberg et al.^36	Prospective	2000	Finland	Elderly	Individuals with a history of stable CVD: CMV titers quartile 1 (n = 99); CMV titers quartile 2 (n = 93); CMV titers quartile 3 (n = 97); CMV titers quartile 4 (n = 94)	The association between CMV infection and QoL impacts in elderly individuals with CVD was investigated using the validated 15D instrument
Auditory performance (n = 4)
Lyutenski et al.^37	Retrospective	2005–2015	Germany	Children	Children with typical patterns of cCMV infection and bilateral severe-to-profound SNHL (n = 23)	The correlation between the severity of typical brain lesions in cCMV infection and cochlear implant outcome was evaluated using the CAP scoring. Speech development was assessed using SIR
Kraaijenga et al.^38	Systematic literature review	2018	NR	Children	Children deafened by cCMV who received cochlear implantation: symptomatic cCMV group (n = 75); Asymptomatic cCMV group (n = 109)	Hearing outcomes in children with cCMV were compared with children without cCMV. Differences in hearing outcomes between children with symptomatic cCMV and children with asymptomatic cCMV were investigated
Yoshida et al.^39	Retrospective	1997 onward	Japan	Children	Children with hearing loss due to cCMV (n = 4)	Auditory skills, speech perception rates, and speech production development rates were compared in children with hearing loss due to cCMV following cochlear implantation versus children with hearing loss not due to cCMV
Iwasaki et al.^40	Prospective	1996–2003	Japan	Children	Children with asymptomatic cCMV and SNHL who received cochlear implantation (n = 2)	Auditory skill development before and after cochlear implantation using the IT-MAIS was evaluated
Cognitive development (n = 20)
Gow et al.^24	Prospective	2004–2007	United Kingdom	General population	Members of the Lothian Birth Cohort 1936, CMV positive (n = 695)	Cognitive outcomes were evaluated in individuals born in 1936 who were seropositive for CMV
Alarcon et al.^41	Prospective	2010–2011	Spain	Infants	Infants with symptomatic cCMV (n = 23)	Utility of clinical, CSF, and neuroimaging findings from the newborn period as predictors of long-term neurodevelopmental outcomes in patients with cCMV was assessed
Fukushima et al.^42	Prospective	2003–2018	Japan	Infants	Infants with cCMV treated with valganciclovir with severe sequelae (n = 9); Infants with cCMV treated with valganciclovir with no or mild sequelae (n = 12)	Neurodevelopmental outcomes for infants with cCMV were evaluated using the Kyoto Scale of Psychological Development
Farkas et al.^43	Cross-sectional	2001–2007	Israel	Children	Children with cCMV (n = 21); Younger subgroup, age 11–42 months (n = 14); Older subgroup, age 43–63 months (n = 7); Normal MRI (n = 11); Abnormal MRI (n = 5)	Associations between ultrasonography and MRI results and neuropsychological outcomes for children with cCMV were investigated
Lofkvist et al.^44	Prospective	2019	Sweden	Children	Children with cCMV (n = 10); Children with the Cx26 mutation (n = 7)	Children with cCMV were compared with well-matched controls whose deafness was caused by the Cx26 mutation
Turriziani Colonna et al.^45	Retrospective	2009–2017	Italy	Children	Children with symptomatic cCMV treated with valganciclovir (n = 12); Children with asymptomatic cCMV treated with valganciclovir (n = 24)	Long-term clinical, audiological, visual, neurocognitive, and behavioral outcomes were evaluated in patients with asymptomatic cCMV
Bevot et al.^46	Prospective	2012	Germany	Children	Children born preterm with early postnatal hCMV infection transmitted via breast milk (n = 20)	K-ABC assessment was used to evaluate the intellectual abilities, simultaneous and sequential processing, and acquired skills of children
Goelz et al.^47	Prospective	1995–2000	Germany	Infants	Infants <1500 g with postnatal CMV infection acquired at up to 3 months (n = 42)	K-ABC assessment was used to evaluate cognitive development in children who acquired CMV infection postnatally
Gunkel et al.^48	Prospective	2007–2010 + 6-year follow-up	Netherlands	Children	Children with a gestational age of ≤30 weeks with postnatal CMV infection (n = 49); Without postnatal CMV infection (n = 307); With symptomatic cCMV (n = 3); With asymptomatic cCMV (n = 30)	Neurodevelopmental outcomes and cognitive function were assessed in children with CMV acquired either congenitally or postnatally, using the BSITD-III, WPPSI-III, and MABC-II assessments
Lee et al.^49	Prospective	2005	United Kingdom	Children	CMV-positive children (n = 864); CMV-negative children (n = 4124)	Speech and language development, attention control, and intelligence were assessed in children with CMV
Hamdani et al.^50	Prospective	2008–2014	France	Adults	CMV-positive adults: Healthy (n = 119); Patients with bipolar disorder (n = 79); Patients with schizophrenia (n = 62)	The effects of CMV infection on cognitive functioning in patients with schizophrenia and bipolar disorder and in healthy controls were analyzed
Chvatalova et al.^51	Prospective	2010–2012	Czech Republic	Adults	CMV-free individuals (n = 135); CMV-infected individuals (n = 148)	The association between CMV infection and intelligence was assessed in university students
Torniainen-Holm et al.^52	Retrospective	2000, 2001, 2011	Finland	Adults	Participants aged ≥30 years living in mainland Finland (n = 6250)	The association between CMV and EBV seropositivity and antibody levels, and cognitive decline, was investigated in adults and elderly individuals diagnosed with dementia
George et al.^53	Prospective	1990–2013	United States	Adults	CMV-positive adults (n = 300); CHD-free adults^b	The association between CMV infection and cognitive decline was investigated
Aiello et al.^54	Prospective	1998–2002	United States	Elderly	Community-dwelling elderly population (n = 1204)	The association between CMV infection and cognitive decline was investigated in a community-dwelling elderly population
Di Benedetto et al.^55	Prospective	2019	Germany	Elderly	CMV-seropositive, aged 64-79 years (n = 102)	Episodic memory, working memory, fluid intelligence, and perceptual speed was assessed in CMV-seropositive elderly individuals
Kawasaki et al.^56	Prospective/cross-sectional	2008–2012	Japan	Elderly	Individuals aged ≥85: CMV IgG antibody: Q1 (2.0–12.3)^c; CMV IgG antibody: Q2 (12.4–18.3)^c; CMV IgG G antibody: Q3 (18.4–29.3)^c; CMV IgG antibody: Q4 (29.4)^c	The association between carotid atherosclerosis, CMV infection, and cognitive decline was examined in elderly individuals
Nimgaonkar et al.^57	Cross-sectional	2016	United States	Elderly	Representative population-based aging cohort (n = 1022)	The contribution of exposure to CMV, HSV-1, HSV-2, or Toxoplasma gondii to cognitive dysfunction and longitudinal cognitive decline was investigated in elderly individuals
Warren-Gash et al.^58	Systematic literature review and meta-analysis	Up to 2017	NR	General population	Patients with dementia or mild cognitive impairment and control groups^b	The effect of any of 8 human herpesviruses on development of dementia or mild cognitive impairment was investigated
Watson et al.^59	NR	2013	United States	General population	Patients with schizophrenia or schizo-affective disorder, their non-psychotic relatives, and screened adult controls (n = 1852)	Neurocognitive performance was measured using the PCH1 analysis, and correlated to participants’ CMV exposure status
Mental health outcomes (n = 9)
Alarcon et al.^41	Retrospective	2010–2011	Spain	Infants	cCMV-seropositive infants with symptomatic infection (n = 28)	The Child Behavior Checklist was used to evaluate behavior
Lofkvist et al.^44	Cross sectional	NR	Sweden	Children	cCMV-seropositive children or children with Cx26 mutation (n = 10)	The mental health of patients was assessed using SDQ
Turriziani Colonna et al.^45	Retrospective	2009–2017	Italy	Children	Patients with symptomatic or asymptomatic cCMV infection treated with valganciclovir (n = 28)	The Child Behavior Checklist was used to evaluate behavior
Ford et al.^60	Cross sectional	NR	United States	Adults	CMV-seropositive adults diagnosed with major depressive disorder (n = 81)	This study evaluated early life stress as a risk factor for CMV infection using the CTQ
Jonker et al.^61	Prospective	2001–2009	Netherlands	Adolescent	CMV-seropositive adolescents (n = 266)	Results from a survey evaluated the association between CMV antibody levels and the presence of any mood disorders, anxiety, and health behaviors
Novotna et al.^62	Retrospective	2000–2001	Czech Republic	Adults	CMV-seropositive adults, aspirants to 2 military specializations (n = 269)	Changes in novelty-seeking behavior were evaluated using the Cloninger TCI questionnaire, following an analysis of possible associations between TCI dimensions and infection status
Phillips et al.^63	Cross sectional	NR	United Kingdom	Elderly	CMV-seropositive patients (n = 90)	GHQ-28 questionnaire results were assessed, focusing on how CMV seropositivity might be associated with psychological morbidity, mental health chronic illness, medication usage, and inflammatory disorders
Rector et al.^64	Cross sectional	NR	United States	Adults	CMV-seropositive patients (n = 329)	Questionnaire results were evaluated looking at any association between measures of psychological stress and CMV antibody levels
Vadini et al.^65	Prospective	2010	Italy	Adults	Women with confirmed primary CMV infection during pregnancy: CMV transmission from mother to child (n = 108)	Patients underwent psychological assessment evaluating perinatal post-traumatic stress symptoms, alexithymic trait, perinatal depressive symptoms and distress personality

Abbreviations. 15D, 15-dimensional; BSITD-III, Bayley Scales of Infant and Toddler Development Third Edition; CAP, Categories of Auditory Performance; cCMV, congenital cytomegalovirus; CHD, coronary heart disease; CMV, cytomegalovirus; CSF, cerebrospinal fluid; CTQ, Childhood Trauma Questionnaire; CVD, cardiovascular disease; DALY, disability-adjusted life years; EBV, Epstein-Barr virus; GHQ-28, General Health Questionnaire-28; hCMV, human cytomegalovirus; HSV-1, herpes simplex virus type 1; HSV-2, herpes simplex virus type 2; IgG, immunoglobulin G; IT-MAIS, Infant-Toddler Meaningful Auditory Integration Scale; K-ABC, Kaufman Assessment Battery for Children; MABC-II, Movement Assessment Battery for Children; MRI, magnetic resonance imaging; NR, not reported; PCH1, The first principal component of heritability; QALY, quality-adjusted life years; QoL, quality of life; QOLI, Quality of Life Inventory; SDQ, Strengths and Difficulties Questionnaire; SIR, Speech Intelligibility Rating; SNHL, sensorineural hearing loss; TCI, Temperament and Character Inventory; WPPSI-III, Wechsler Preschool and Primary Scale of Intelligence Third Edition.

^aNewborn, up to 1 month; infants, 2 months-2 years; children, 3–10 years; adolescents, 11-18 years; adults, 19+ years; elderly, 60+ years.

^bSpecific subset of the study population.

^cSample size was not reported.

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Data availability statement

The data summarized from this review are from published articles and are publicly available.