Host RNA Expression Profiles and Protein Biomarkers in Neonatal Herpes Simplex Virus Infection

NCT ID: NCT05226949

Last Updated: 2022-12-28

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Total Enrollment

159 participants

Study Classification

OBSERVATIONAL

Study Start Date

2022-01-01

Study Completion Date

2022-04-30

Brief Summary

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This study seeks to identify and test host RNA expression profiles in context to protein biomarkers in dried blood spot samples as novel diagnostic markers of neonatal herpes simplex virus infection and to improve the understanding of the pathogenesis of the disease.

Detailed Description

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Background:

Herpes Simplex Virus (HSV) infection in newborns is uncommon but can be devastating and is associated with significant morbidity and mortality. The diagnosis of neonatal HSV infection is challenging because maternal genital herpes often is asymptomatic and the clinical presentation in newborns can be nonspecific, especially in the early disease stages. This results in late diagnosis and potentially terrible consequences for the newborn. The reason why some newborns develop severe disease due to HSV infection is unknown. It has been suggested that immunologic differences in early infancy are the key to further advances. Host RNA expression profiling, transcriptomics, of the host response to infections has shown great potential as clinical tool for diagnostics and for unveiling molecular disease mechanisms. As previously shown, reliable host RNA expression data can be obtained from neonatal dried blood spot (DBS) samples by RNA-sequencing. Proteomic analysis has the potential to simultaneously identify hundreds of protein biomarkers and immune cell populations allowing for detailed mapping of disease immunological pathways.

Method:

A nationwide retrospective case-control study of all newborns with HSV infection in Denmark from 2010 through 2019. DBS samples will be obtained from the Danish Neonatal Screening Biobank, Statens Serum Institut. RNA sequencing and proteomic analyses will be performed at the Danish Center for Neonatal Screening, Department of Congenital Disorders, Statens Serum Institut. Cases will be randomly assigned to a "Discovery cohort" and compared to a control group of newborns matched on gestational age, sex and birthweight will be included.

Time frame:

Sample identification/recruiting: January 1st to January 31st 2022. Sample analysis (RNA sequencing and proteomic analysis): February 1st to April 30th 2022.

Perspectives:

New molecular-based diagnostic tools complementary to conventional methods may improve early diagnosis of neonatal HSV infections and lead to optimised management. In addition, understanding of the pathogenesis at a molecular level of severe disease manifestations of the disease, could form the basis for development of novel interventions for better prevention and treatment.

Conditions

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Neonatal Herpes Simplex Infection Neonatal HSV Infection Neonatal Infection Newborn; Infection Herpes Simplex Virus Infection Neonatal Sepsis Neonatal Death Viral Infection

Study Design

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Observational Model Type

CASE_CONTROL

Study Time Perspective

RETROSPECTIVE

Study Groups

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Cases

54 newborns with neonatal HSV infection.

Interventions:

Diagnostic test and disease pathogenesis: Host RNA expression profiling by RNA sequencing and proteomic analyses. Cases will be randomly assigned to a "Discovery Cohort" (identification of diagnostic RNA and proteomic profiles).

No interventions assigned to this group

Controls

108 newborns without infection.

Interventions:

Diagnostic test and disease pathogenesis: Host RNA expression profiling by RNA sequencing and proteomic analyses. Controls will be randomly assigned to a "Discovery Cohort" (identification of diagnostic RNA and proteomic profiles).

No interventions assigned to this group

Eligibility Criteria

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Inclusion Criteria

1. cases of newborns aged 0-28 days with verified HSV infection (positive HSV PCR in blood, cerebrospinal fluid and/or swab sample)
2. controls of newborns without infection matched on gestational age, sex and birthweight

Exclusion Criteria

1. dried blood spot samples that are not allowed to be used for research
2. dried blood spots samples containing insufficient amount of blood for research
Minimum Eligible Age

0 Days

Maximum Eligible Age

28 Days

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Statens Serum Institut

OTHER

Sponsor Role collaborator

Rigshospitalet, Denmark

OTHER

Sponsor Role lead

Responsible Party

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Kia Hee Schultz Dungu

Principal Investigator

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Kia Hee Schultz Dungu, MD

Role: PRINCIPAL_INVESTIGATOR

Rigshospitalet, Denmark

Ulrikka Nygaard, Ass Prof PhD

Role: STUDY_CHAIR

Rigshospitalet, Denmark

Locations

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Department of Paediatrics and Adolescent Medicine, Rigshospitalet

Copenhagen, , Denmark

Site Status

Department of Congenital Disorders, Statens Serum Institut

Copenhagen, , Denmark

Site Status

Countries

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Denmark

Other Identifiers

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H-21009288-HSV

Identifier Type: -

Identifier Source: org_study_id