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.
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clinical and laboratory characteristics of COVID-19 associated encephalitis/encephalopathy
Timeframe: 2 year
biomarkers and risk factors of MIS-C
Timeframe: 2 year