Host RNA Expression Profiles and Protein Biomarkers in Neonatal Herpes Simplex Virus Infection
Condition: Neonatal Herpes Simplex Infection; Neonatal HSV Infection; Neonatal Infection; Newborn; Infection; Herpes Simplex Virus Infection; Neonatal Sepsis; Neonatal Death; Viral Infection
MeSH terms: Infections; Communicable Diseases; Virus Diseases; Herpes Simplex; Neonatal Sepsis; Pregnancy Complications, Infectious; Perinatal Death
Study type: Observational

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.
    

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.
      
Biospecimen description: 
      Dried blood spot samples will be obtained from the Danish Neonatal Screening Biobank, Statens
      Serum Institut. RNA sequencing and proteomic analyses (in total 12 ul whole blood) will be
      performed at the Danish Center for Neonatal Screening, Department of Congenital Disorders,
      Statens Serum Institut.