Abstract
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.
Highlights
Congenital CMV infection affects 0.5–1% of all live births worldwide, making it the leading cause of sensorineural hearing loss (SNHL) in childhood
By applying whole-blood transcriptomics, we sought to identify the differences in gene expression profiles between infants with symptomatic and asymptomatic Congenital cytomegalovirus (cCMV) infection and their association with late-onset SNHL
The diagnosis of infants with symptomatic and asymptomatic cCMV infection was established in the first week of life per standard of care, and blood samples were obtained at study enrollment the second or third week of life
Summary
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. Analysis of host blood transcriptional profiles has provided significant insights regarding disease pathogenesis, diagnosis, assessment of clinical severity and improved patient classification of children with varied ailments[10,11,12,13,14] This approach has been explored in a small cohort of infants with cCMV infection utilizing dried blood spots, identifying preliminary associations of transcriptional signatures with long-term outcomes[15]. Our data show that blood immune profiles between symptomatic and asymptomatic infants with cCMV infection are indistinguishable, suggesting that host responses to congenital CMV infection are similar irrespective of the clinical classification. We identify a 16-gene classifier set that distinguishes with 92% accuracy infants who would develop late-onset SNHL, suggesting the value of host genomic responses as a biomarker for hearing loss in congenital CMV infection
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