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Host factors contributing to susceptibility to COVID-19 disease

导致对 COVID-19 疾病易感性的宿主因素

基本信息

批准号：
10692224
负责人：
Helen Su
金额：
$ 47.05万
依托单位：
NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES
依托单位国家：
美国
项目类别：
财政年份：
资助国家：
美国
起止时间：
至
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10692224
关键词：
2019-nCoV Acute Affect Agreement American Americas Autoantibodies Biochemical Biological Markers COVID-19 Child Collaborations Convalescence Defect Disease Double-Stranded RNA Enrollment Family member Far East Genetic Genetic Determinism Genome Health Sciences Hematopoiesis Human Human Genetics Immune Immune response In Vitro Individual Infection Institutional Review Boards Integration Host Factors Interferons International Intramural Research Program Italy Kinetics Knowledge Life Memory Middle East Molecular Multisystem Inflammatory Syndrome in Children National Institute of Allergy and Infectious Disease National Institute of Arthritis, and Musculoskeletal, and Skin Diseases National Institute of Dental and Craniofacial Research Neurologic Outcome Paper Pathogenesis Pathway interactions Patients Persons Population Genetics Predisposition Principal Investigator Program Research Project Grants Protocols documentation Recording of previous events Research Research Personnel Role SARS-CoV-2 infection Sampling Susceptibility Gene Therapeutic Intervention University Health Services Validation Variant Work acute infection adaptive immune response comorbidity consanguineous family coronavirus disease genetic approach genetic variant interest molecular targeted therapies respiratory response sensor severe COVID-19 young adult

项目摘要

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 2022, we extended our previous discovery of genetic and acquired defects in type I IFN responses as a cause of severe or critical COVID-19. We characterized the kinetics of neutralizing autoantibodies against type I IFN and found that these were dynamically produced during acute infection but decreased during convalescence, suggesting that disease pathogenesis might involve a memory response with implications for detecting individuals with such autoantibodies before infection. In various collaborations with the NIAID COVID-19 Consortium and the COVID Human Genetic Effort, we have also assisted with the characterization of potential role of neurological biomarkers and clonal hematopoiesis in respiratory COVID-19, as well as potential genetic contribution to other forms of SARS-CoV-2 infection (MIS-C, pernio). Finally, ongoing work led by our research group is investigating the potential role of genetic variants of dsRNA sensors in COVID-19 outcome.

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.制定了 IRB 批准的涉及送入样本的新冠病毒方案，以促进其他缺乏自己的新冠病毒方案的中心的研究。我们与新冠病毒人类基因组合作，并通过这次国际合作发表了多篇论文。 In FY 2022, we extended our previous discovery of genetic and acquired defects in type I IFN responses as a cause of severe or critical COVID-19. We characterized the kinetics of neutralizing autoantibodies against type I IFN and found that these were dynamically produced during acute infection but decreased during convalescence, suggesting that disease pathogenesis might involve a memory response with implications for detecting individuals with such autoantibodies before infection. In various collaborations with the NIAID COVID-19 Consortium and the COVID Human Genetic Effort, we have also assisted with the characterization of potential role of neurological biomarkers and clonal hematopoiesis in respiratory COVID-19, as well as potential genetic contribution to other forms of SARS-CoV-2 infection (MIS-C, pernio).最后，我们的研究小组领导的正在进行的工作正在调查 dsRNA 传感器的遗传变异在 COVID-19 结果中的潜在作用。