Cytomegalovirus DNA Detection by Polymerase Chain Reaction in Cerebrospinal Fluid of Infants With Congenital Infection: Associations With Clinical Evaluation at Birth and Implications for Follow-up

Goycochea-Valdivia, Walter-Alfredo; Baquero-Artigao, Fernando; Rabes, T. del Rosal; Frick, M A; Rojo, Pablo; Echeverría, María-Juncal; Noguera-Julián, Antoni; Bringué, X.; Saavedra-Lozano, Jesús; Vives-Oñós, Isabel; Moliner, Ernesto Clar; Cilleruelo, M.a José; Cuadrado, Irene; Colino, Elena; Castells, Laura; Tagarro, Alfredo; Vilas, Javier; Soler‐Palacín, Pere; Blázquez‐Gamero, Daniel

doi:10.1093/cid/cix105

Cited by 22 publications

(17 citation statements)

References 25 publications

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“…These findings have been replicated since then for amniotic fluid [70][71][72] and for urine [73][74][75] and blood at birth [70,74,76], and their association both with the risk of developing sensorineural hearing loss and other cCMV-associated sequelae have been studied. A positive determination of CMV DNA in the cerebrospinal fluid at birth has also recently been associated with symptoms in the cCMV-infected neonate [77]. The reason why viruria at birth correlates with cCMV disease in other organs but does not seem to cause kidney damage in cCMV-infected infants is intriguing.…”

Section: Discussionmentioning

confidence: 99%

Renal Involvement in Congenital Cytomegalovirus Infection: A Systematic Review

Ríos-Barnés¹,

Fortuny

Alarcón

et al. 2021

Microorganisms

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Background: Congenital cytomegalovirus (cCMV) infection is the most frequent mother-to-child transmitted infection worldwide and a prevalent cause of neonatal disease and long-term morbidity. The kidney is a target organ for CMV, which replicates in renal tubules and is excreted in large quantities in urine for years in children with cCMV infection. Nonetheless, kidney disease has rarely been reported in cCMV-infected patients. Objective: We aimed to describe the available data on renal involvement in patients with cCMV infection at the pathologic, functional, anatomical, and/or clinical levels. Methods: A systematic search was performed in the MEDLINE/PubMed, SCOPUS, and Cochrane databases. Studies describing any renal involvement in fetuses or neonates aged ≤3 weeks at diagnosis of microbiologically confirmed cCMV infection were eligible. Results: Twenty-four articles were included, with a very low level of evidence. Pathologic findings in autopsy studies universally described CMV typical inclusion bodies in tubular cells. No functional studies were identified. cCMV infection was not associated with an increased risk of kidney malformations. Congenital nephrotic syndrome was the most common clinical condition associated with cCMV, but a causal relationship cannot be established. Conclusions: Typical pathological features of cCMV infection are very common in renal tissue, but they do not seem to entail significant consequences at the anatomical or clinical levels.

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Section: Discussionmentioning

confidence: 99%

Renal Involvement in Congenital Cytomegalovirus Infection: A Systematic Review

Ríos-Barnés¹,

Fortuny

Alarcón

et al. 2021

Microorganisms

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“…Persistent viral replication in the inner ear structures may play a role [7,8], but testing such a hypothesis is challenging. The largest available series that retrospectively explored the role of CMV detection in the cerebrospinal fluid (CSF) failed to find a correlation between positive CMV CSF polymerase chain reaction (PCR) and longterm hearing and neurological outcomes [9]. Some studies suggested that higher blood viral load in early infancy may be associated with SNHL [8,10,11], but other studies have not identified such an association [12,13].…”

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confidence: 99%

Blood Viral Load in Symptomatic Congenital Cytomegalovirus Infection

Marsico

Aban

Kuo

et al. 2018

The Journal of Infectious Diseases

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Background Viral loads (VLs) frequently are followed during treatment of symptomatic congenital cytomegalovirus disease, but their predictive value is unclear. Methods Post hoc analysis of 2 antiviral studies was performed. Seventy-three subjects were treated for 6 weeks and 47 subjects were treated for 6 months. Whole blood VL was determined by real-time polymerase chain reaction before and during therapy. Results Higher baseline VL was associated with central nervous system involvement (3.82 log, range 1–5.65 vs 3.32 log, range 1–5.36; P = .001), thrombocytopenia (3.68 log, range 1–5.65 vs 3.43 log, range 1–5.36; P = .03), and transaminitis at presentation (3.73 log, range 1–5.60 vs 3.39 log, range 1–5.65; P = .009), but with overlap in the amount of virus detected between groups. In subjects treated for 6 months, lower VL at presentation correlated with better hearing outcomes at 12 months, but VL breakpoints predictive of hearing loss were not identified. Sustained viral suppression during 6 months of therapy correlated with better hearing outcomes at 6, 12, and 24 months (P = .01, P = .0007, P = .04), but a majority without viral suppression still had improved hearing. Conclusions In infants with symptomatic congenital cytomegalovirus disease, higher whole blood VL before initiation of antiviral therapy has no clinically meaningful predictive value for long-term outcomes.

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“…Despite the wide range of clinical manifestations, the determinants that drive the observed symptomatology (or lack thereof) are largely unknown. Likewise, there are no factors, including blood CMV loads, that have shown to reliably predict the development of late-onset SNHL in both symptomatic and asymptomatic infants 9,[23][24][25][26][27] . Furthermore, although infants with symptomatic disease demonstrate higher rates of SNHL than those that are asymptomatic, the subsets within both symptomatic and asymptomatic infants who are at highest risk of developing SNHL are not well defined 28 .…”

Section: Discussionmentioning

confidence: 99%

Blood genome expression profiles in infants with congenital cytomegalovirus infection

Ouellette

Sánchez

et al. 2020

Nat Commun

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Congenital CMV infection (cCMVi) affects 0.5-1% of all live births worldwide, making it the leading cause of sensorineural hearing loss (SNHL) in childhood. The majority of infants with cCMVi have normal hearing at birth, but are at risk of developing late-onset SNHL. Currently, we lack reliable biomarkers to predict the development of SNHL in these infants. Here, we evaluate blood transcriptional profiles in 80 infants with cCMVi (49 symptomatic, 31 asymptomatic), enrolled in the first 3 weeks of life, and followed for 3 years to assess emergence of late-onset SNHL. The biosignatures of symptomatic and asymptomatic cCMVi are indistinguishable, suggesting that immune responses of infants with asymptomatic and symptomatic cCMVi are not different. Random forest analyses of initial samples in infants with cCMVi, irrespective of their clinical classification, identify a 16-gene classifier signature associated with the development of SNHL with 92% accuracy, suggesting its potential value as a biomarker.

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Cytomegalovirus DNA Detection by Polymerase Chain Reaction in Cerebrospinal Fluid of Infants With Congenital Infection: Associations With Clinical Evaluation at Birth and Implications for Follow-up

Abstract: A positive hCMV-PCR result in CSF is associated with symptomatic cCMV and SNHL at birth. However, no differences in neuroimaging studies, plasma viral load, or outcomes at 6 months were found. These results suggest that hCMV-PCR in CSF may not be a useful prognostic marker in cCMV.

Cited by 22 publications

References 25 publications

Renal Involvement in Congenital Cytomegalovirus Infection: A Systematic Review

Renal Involvement in Congenital Cytomegalovirus Infection: A Systematic Review

Blood Viral Load in Symptomatic Congenital Cytomegalovirus Infection

Blood genome expression profiles in infants with congenital cytomegalovirus infection

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