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

Sponsor

Rigshospitalet, Denmark (Other)

Overall Status

Active, not recruiting

CT.gov ID

NCT05226949

Collaborator

Statens Serum Institut (Other)

162

Enrollment

Locations

14.9

Anticipated Duration (Months)

Patients Per Site

5.4

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Neonatal Herpes Simplex Infection Neonatal HSV Infection Neonatal Infection Newborn; Infection Herpes Simplex Virus Infection Neonatal Sepsis Neonatal Death Viral Infection

Detailed Description

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.

Study Design

Study Type:

Observational

Anticipated Enrollment :

162 participants

Observational Model:

Case-Control

Time Perspective:

Retrospective

Official Title:

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

Actual Study Start Date :

Jan 1, 2022

Actual Primary Completion Date :

Feb 28, 2022

Anticipated Study Completion Date :

Mar 31, 2023

Arms and Interventions

Arm	Intervention/Treatment
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).
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).

Outcome Measures

Primary Outcome Measures

Host RNA expression and proteomic profiles [Admission, age 0-28 days]
To identify specific host RNA expression and proteomic profiles in dried blood spot samples from newborns with HSV infection

Secondary Outcome Measures

Disease pathogenesis [Admission, age 0-28 days]
Mapping of disease immunological pathways by simultaneous host RNA expression profiling and proteomic analysis
Application of known host RNA profiles [Admission, age 0-28 days]
To test host RNA profiles published in other studies, e.g. based on the genes IFI44L and FAM89A

Eligibility Criteria

Criteria

Ages Eligible for Study:

0 Days to 28 Days

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

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

Exclusion Criteria:

dried blood spot samples that are not allowed to be used for research
dried blood spots samples containing insufficient amount of blood for research

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Department of Paediatrics and Adolescent Medicine, Rigshospitalet	Copenhagen		Denmark	2100
2	Department of Congenital Disorders, Statens Serum Institut	Copenhagen		Denmark	2300