Investigation of Prognostic Biomarkers, Host Factors and Viral Factors for COVID-19 in Children

Summary

Background and objective From this April, there was a COVID-19 outbreak in Taiwan. The first fatal case of pediatric COVID-19 encephalitis was reported on April 19, 2022 and fatal fulminant cerebral edema in other 4 children with COVID-19 encephalitis was reported within 1 month from Taiwan CDC registry. To date, around 700,000 children got COVID-19 recently. Several children developed MIS-C (multi-system inflammatory syndrome in children)-related shock about 2-6 weeks after COVID-19. Since both COVID-19 associated encephalopathy/ encephalitis and MIS-C are life-threatening, it is urgent to delineate its prognostic biomarker, host genetic factors, immunopathogenesis and viral pathogenesis.

Methods Pediatricians will enroll cases of both COVID-19 associated encephalopathy/ encephalitis and MIS-C from several hospitals and medical centers. Their clinical manifestations, lab findings, severity and outcomes will be collected. Clinical assessment of all the systems will be performed. Blood, nasopharyngeal swab and stool will be collected at acute, subacute and convalescent stages for whole exome sequencing, immunopathogenesis including chemokine/cytokine, T/B lymphocyte subset, SARS-CoV2 specific Ab/T/B cell, T and B cell repertoire, viral pathogenesis including multiple viral detection, persistence of fecal SARS-COVID-2 as well as respiratory and gut microbiota. We will establish the animal models for COVID-19 associated encephalopathy/encephalitis and MIS-C, based on the K18-hACE2 or R26R-AGP mouse models established in NTU animal center. Moreover, specific viral or host factors involved in regulating the pathogenesis and immune responses can be investigated, to optimize the protocol for further improvement of the animal models and also to help identify the putative therapeutic targets.

Expected results We will delineate the clinical and laboratory characteristics of COVID-19 associated encephalopathy and encephalitis, the role of immune, virology, genetics mechanism in pathophysiology, and will optimize the treatment algorithm based on the result of this study. We also expect that the important biomarkers and risk factors associated with clinical outcome and severity, the immunopathogenesis of MIS-C, host genetic factors and the viral pathogenesis and microbiota associated with MIS-C will be found.

Conditions

• COVID-19-Associated Encephalitis
• Multisystem Inflammatory Syndrome in Children

Interventions

OTHER

delineate its prognostic biomarker, host genetic factors, immunopathogenesis and viral pathogenesis

We will delineate the clinical and laboratory characteristics of COVID-19 associated encephalopathy and encephalitis, the role of immune, virology, genetics mechanism in pathophysiology, and will optimize the treatment algorithm based on the result of this study. We also expect that the important biomarkers and risk factors associated with clinical outcome and severity, the immunopathogenesis of MIS-C, host genetic factors and the viral pathogenesis and microbiota associated with MIS-C will be found.

Sponsors & Collaborators

• Chang Gung Medical Foundation

  collaborator OTHER

• National Cheng-Kung University Hospital

  collaborator OTHER

• Chi Mei Medical Hospital

  collaborator OTHER

• Mackay Memorial Hospital

  collaborator OTHER

• Tri-Service General Hospital

  collaborator OTHER

• National Health Research Institutes, Taiwan

  collaborator OTHER

• National Science and Technology Council

  collaborator FED

• National Taiwan University Hospital

  lead OTHER

Principal Investigators

• Luna-Yin Chang, professor · National Taiwan University Hospital

Eligibility

Max Age

18 Years

Sex

ALL

Healthy Volunteers

Yes

Timeline & Regulatory

Start

2022-08-01

Primary Completion

2025-07-31

Completion

2025-07-31

Countries

• Taiwan

Study Locations