Clinical trial NCT05226949: Host RNA Expression Profiles and Protein Biomarkers in Neonatal Herpes Simplex Virus Infection
Official title: Host RNA Expression Profiles and Protein Biomarkers in Neonatal Herpes Simplex Virus Infection
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Neonatal Herpes Simplex Infection
Neonatal HSV Infection
Neonatal Infection
Newborn; Infection
Herpes Simplex Virus Infection
Neonatal Sepsis
Neonatal Death
Viral Infection
Lead sponsor: Rigshospitalet, Denmark
Sponsor class: OTHER
Collaborators: name: Statens Serum Institut
First posted: 2022-02-07
Enrollment: 159
Sex: ALL
Minimum age (years): 0
Maximum age (years): 28
Standard ages: CHILD
Accepts healthy volunteers: no
Observational model: CASE_CONTROL
Time perspective: RETROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Newborns aged 0-28 days with verified HSV infection in Denmark from 2010 through 2019.

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.

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.

Eligibility criteria: 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

Primary outcomes:
measure: Host RNA expression and proteomic profiles
timeFrame: Admission, age 0-28 days
Secondary outcomes:
measure: Disease pathogenesis
timeFrame: Admission, age 0-28 days
measure: Application of known host RNA profiles
timeFrame: Admission, age 0-28 days
Other outcomes:
Locations:
city: Copenhagen
country: Denmark
facility: Department of Paediatrics and Adolescent Medicine, Rigshospitalet
city: Copenhagen
country: Denmark
facility: Department of Congenital Disorders, Statens Serum Institut
Study officials:
affiliation: Rigshospitalet, Denmark
name: Kia Hee Schultz Dungu, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Rigshospitalet, Denmark
name: Ulrikka Nygaard, Ass Prof PhD
role: STUDY_CHAIR
References: