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Principal Investigator: Helen Chun-Hui Su
Organization: NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES
Fiscal Year: 2023
Award: $478,359
Funding agency: National Institute of Allergy and Infectious Diseases
These studies have been organized as part of a broader effort among multiple principal investigators in the Intramural Research Programs of NIAID, NIDCR, NCI, and NIAMS, as well as a research collaborative agreement with investigators at the American Genome Center/Uniformed Services University of the Health Sciences. We have assembled an international collaboration to study patients enrolled at centers in Italy, which was later expanded to include centers in East Asia, the Middle East, and the Americas. An IRB-approved COVID protocol involving send-in samples was written to facilitate studies at other centers lacking their own COVID protocols. We have partnered with the COVID-Human Genetic Effort, and multiple papers have come out of this international collaboration.
In FY 2023, we extended our previous discovery of genetic and acquired defects in type I IFN responses as a cause of severe or critical COVID-19. In various collaborations with the NIAID COVID-19 Consortium and the COVID Human Genetic Effort, we have also contributed to the identification of new monogenic forms of multisystem inflammatory syndrome in children (MIS-C) following SARS-CoV-2 infection. Through these large international collaborative efforts, children were discovered with rare biallelic loss-of-function mutations in the OAS1, OAS2, or RNASEL genes. These mutations result in increased proinflammatory cytokines leading to disease. This discovery can improve molecular diagnosis of children at risk for developing a rare complication of SARS-CoV-2 infection. They also provide scientific rationale for molecular targeting of a pathway whose dysregulation is central to this condition. Finally, ongoing work led by our research group is investigating the potential role of genetic variants of dsRNA sensors in COVID-19 outcome.
Terms: <0-11 years old><2019 novel corona virus><2019 novel coronavirus><2019-nCoV><Acute><Affect><Agreement><Allelic Loss><American><Americas><Biochemical><COVID><COVID-19><COVID-19 infection><COVID-19 predisposition><COVID-19 susceptibility><COVID-19 virus><COVID-19 virus infection><COVID-19 vulnerability><COVID19><COVID19 infection><COVID19 virus><CV-19><CV19><Child><Child Youth><Children (0-21)><CoV disease><CoV-2><CoV2><Collaborations><Complication><Convalescence><Coronavirus disease 2019 predisposition><Coronavirus disease 2019 susceptibility><Coronavirus disease 2019 vulnerability><Defect><Disease><Disorder><Double-Stranded RNA><East Asia><Eastern Asia><Family member><Far East><Gene variant><Genes><Genetic><Genetic Alteration><Genetic Change><Genetic Determinism><Genetic defect><Genome><Health Sciences><History><Host Factor><Host Factor Protein><Human><Human Genetics><IFN><IRB><IRBs><Immune><Immune response><Immunes><Immunological response><In Vitro><Individual><Inflammatory><Innate Immune Response><Institutional Review Boards><Integration Host Factors><Interferons><International><Intramural Program><Intramural Research Program><Investigators><Italy><Knowledge><Life><Loss of Heterozygosity><MIS-C><Middle East><Modern Man><Molecular><Molecular Diagnosis><Molecular Target><Multiorgan Inflammatory Syndrome in Children><Multisystem Inflammatory Syndrome in Children><Mutation><NIAID><NIAMS><NIDCR><NIDR><National Institute of Allergy and Infectious Disease><National Institute of Arthritis, and Musculoskeletal, and Skin Diseases><National Institute of Dental Research><National Institute of Dental and Craniofacial Research><Outcome><P01 Mechanism><P01 Program><Paper><Pathogenesis><Pathway interactions><Patients><Persons><Population Genetics><Predisposed to COVID-19><Predisposed to SARS-CoV-2><Predisposed to Severe acute respiratory syndrome coronavirus 2><Predisposition><Predisposition gene><Principal Investigator><Program Project Grant><Program Research Project Grants><Protocol><Protocols documentation><Recording of previous events><Research><Research Personnel><Research Program Projects><Researchers><Risk><Role><SARS corona virus 2><SARS-CO-V2><SARS-COVID-2><SARS-CoV-2><SARS-CoV-2 infection><SARS-CoV-2 predisposition><SARS-CoV-2 susceptibility><SARS-CoV-2 vulnerability><SARS-CoV2><SARS-CoV2 infection><SARS-associated corona virus 2><SARS-associated coronavirus 2><SARS-coronavirus-2><SARS-related corona virus 2><SARS-related coronavirus 2><SARSCoV2><Sampling><Severe Acute Respiratory Coronavirus 2><Severe Acute Respiratory Distress Syndrome CoV 2><Severe Acute Respiratory Distress Syndrome Corona Virus 2><Severe Acute Respiratory Distress Syndrome Coronavirus 2><Severe Acute Respiratory Syndrome CoV 2><Severe Acute Respiratory Syndrome-associated coronavirus 2><Severe Acute Respiratory Syndrome-related coronavirus 2><Severe acute respiratory syndrome associated corona virus 2><Severe acute respiratory syndrome coronavirus 2><Severe acute respiratory syndrome coronavirus 2 infection><Severe acute respiratory syndrome coronavirus 2 predisposition><Severe acute respiratory syndrome coronavirus 2 susceptibility><Severe acute respiratory syndrome coronavirus 2 vulnerability><Severe acute respiratory syndrome related corona virus 2><Susceptibility><Susceptibility Gene><Therapeutic Intervention><University Health Services><Validation><Variant><Variation><Work><Writing><Wuhan coronavirus><adaptive immune response><adult youth><after COVID-19 infection><after SARS-CoV-2 infection><after SARS-CoV2 infection><after infection by SARS-CoV-2><after severe acute respiratory distress syndrome CoV-2 infection><allele variant><allelic variant><co-morbid><co-morbidity><comorbidity><consanguineous family><consanguineous kindreds><consanguineous pedigree><corona virus disease><corona virus disease 2019><coronavirus disease><coronavirus disease 2019><coronavirus disease 2019 infection><coronavirus disease 2019 virus><coronavirus disease-19><coronavirus disease-19 virus><coronavirus infectious disease-19><cytokine><dsRNA><following COVID-19 infection><following SARS-CoV-2 infection><following SARS-CoV2 infection><following infection by SARS-CoV-2><following severe acute respiratory distress syndrome CoV-2 infection><genetic approach><genetic determinant><genetic strategy><genetic variant><genome mutation><genomic variant><hCoV19><histories><host response><immune system response><immunoresponse><improved><infected with COVID-19><infected with COVID19><infected with SARS-CoV-2><infected with SARS-CoV2><infected with coronavirus disease 2019><infected with severe acute respiratory syndrome coronavirus 2><intervention therapy><kids><life-threatening COVID><life-threatening COVID-19><life-threatening SARS-CoV-2><life-threatening coronavirus disease><life-threatening coronavirus disease 2019><life-threatening severe acute respiratory syndrome coronavirus 2><loss of function mutation><molecular targeted therapeutics><molecular targeted therapies><molecular targeted treatment><multisystem inflammatory syndrome of children><nCoV2><participant enrollment><pathway><patient enrollment><pediatric inflammatory multisystem syndrome><post SARS-CoV-2 infection><predisposed to Coronavirus disease 2019><predisposing gene><previous COVID-19 infection><previous SARS-CoV-2 infection><previous SARS-CoV2 infection><previous severe acute respiratory distress syndrome CoV-2 infection><prior COVID-19 infection><prior SARS-CoV-2 infection><prior SARS-CoV2 infection><prior severe acute respiratory distress syndrome CoV-2 infection><respiratory><response><sensor><serious COVID><serious COVID-19><serious SARS-CoV-2><serious coronavirus disease><serious coronavirus disease 2019><serious severe acute respiratory syndrome coronavirus 2><severe COVID><severe COVID-19><severe COVID19><severe SARS-CoV-2><severe coronavirus disease><severe coronavirus disease 19><severe coronavirus disease 2019><severe severe acute respiratory syndrome coronavirus 2><social role><susceptibility allele><susceptibility locus><susceptibility variant><susceptible to COVID-19><susceptible to Coronavirus disease 2019><susceptible to SARS-CoV-2><susceptible to Severe acute respiratory syndrome coronavirus 2><validations><variant of interest><young adult><young adulthood><youngster>