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Principal Investigator: Helen Chun-Hui Su
Organization: NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES
Fiscal Year: 2024
Award: $628,084
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 and other institutes, 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 2024, 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 collaborations with the NIAID COVID-19 Consortium and the COVID Human Genetic Effort, we have also contributed to the identification of monogenic NF-kB2 deficiency as a cause for the development of neutralizing autoantibodies against type I IFNs. This is a new genetic etiology for acquired virus susceptibility. Its discovery provided evidence for NF-kB-dependent thymic dysregulation as a major factor contributing to disease pathogenesis. Finally, ongoing work led by our research group is investigating the potential role of other genetic variants, including those of dsRNA sensors, in COVID-19 outcome.
Terms: <0-11 years old><2019 novel corona virus><2019 novel coronavirus><2019-nCoV><Affect><Agreement><American><Americas><Autoantibodies><Biochemical><COVID-19><COVID-19 infection><COVID-19 predisposition><COVID-19 susceptibility><COVID-19 virus><COVID-19 virus infection><COVID-19 vulnerability><COVID19 infection><COVID19 virus><CV-19><Child><Child Youth><Children (0-21)><CoV-2><CoV2><Collaborations><Complication><Convalescence><Coronavirus Infectious Disease 2019><Coronavirus disease 2019 predisposition><Coronavirus disease 2019 susceptibility><Coronavirus disease 2019 vulnerability><Defect><Development><Disease><Disorder><Double-Stranded RNA><East Asia><Eastern Asia><Family member><Far East><Gene variant><Genetic><Genetic Determinism><Genetic Predisposition><Genetic Predisposition to Disease><Genetic Susceptibility><Genetic propensity><Genome><Health Sciences><History><Host Factor><Host Factor Protein><Human><Human Genetics><IFN><IRB><IRBs><Immune><Immune response><Immunes><Immunoglobulin Enhancer-Binding Protein><Immunological response><In Vitro><Individual><Inherited Predisposition><Inherited Susceptibility><Innate Immune Response><Institutional Review Boards><Integration Host Factors><Interferons><International><Intramural Program><Intramural Research Program><Investigators><Italy><Knowledge><Life><MIS-C><Middle East><Modern Man><Molecular><Multiorgan Inflammatory Syndrome in Children><Multisystem Inflammatory Syndrome in Children><NF-kB><NF-kappa B><NF-kappaB><NFKB><NIAID><National Institute of Allergy and Infectious Disease><Nuclear Factor kappa B><Nuclear Transcription Factor NF-kB><Other Genetics><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><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><Thymus><Thymus Gland><Thymus Proper><Thymus Reticuloendothelial System><Transcription Factor NF-kB><University Health Services><Validation><Variant><Variation><Virus><Work><Writing><Wuhan coronavirus><acute COVID-19><acute SARS-CoV-2 infection><acute phase of COVID-19><acute phase of SARS-CoV-2 infection><adaptive immune response><adult youth><allele variant><allelic variant><autoimmune antibody><autoreactive antibody><co-morbid><co-morbidity><comorbidity><consanguineous family><consanguineous kindreds><consanguineous pedigree><coronavirus disease 2019><coronavirus disease 2019 infection><coronavirus disease 2019 virus><coronavirus disease-19><coronavirus disease-19 virus><coronavirus infectious disease-19><developmental><dsRNA><genetic approach><genetic determinant><genetic etiology><genetic mechanism of disease><genetic strategy><genetic variant><genetic vulnerability><genetically predisposed><genomic variant><hCoV19><histories><host response><immune system response><immunoresponse><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><kappa B Enhancer Binding Protein><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><molecular targeted therapeutics><molecular targeted therapies><molecular targeted treatment><multisystem inflammatory syndrome of children><nCoV2><nuclear factor kappa beta><participant enrollment><pathway><patient enrollment><pediatric inflammatory multisystem syndrome><predisposed to Coronavirus disease 2019><predisposing gene><respiratory><response><self reactive antibody><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><vulnerable to COVID-19><vulnerable to Coronavirus disease 2019><vulnerable to SARS-CoV-2><vulnerable to Severe acute respiratory syndrome coronavirus 2><young adult><young adulthood><youngster>