Etiology and outcome of MIS-C

MIS-C 的病因和结果

• 批准号: 10198501
• 负责人: Anne Davidson
• 金额: $ 149.19万
• 依托单位: FEINSTEIN INSTITUTE FOR MEDICAL RESEARCH
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-08-27 至 2024-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10198501
• 关键词: 2019-nCoV; Acute; Acute Disease; Affinity; Alleles; Antibodies; Antibody Repertoire; Antibody Response; Blood; Blood specimen; COVID-19; Caring; Child; Childhood; Clinical; Control Groups; DNA; Diagnosis; Disease; Enrollment; Etiology; Exhibits; Fc Receptor; Genes; Goals; Health; High Pressure Liquid Chromatography; Hospitalization; Immune Complex Diseases; Immunity; Immunoglobulin G; Immunoglobulin M; Infection; Inflammation Mediators; Inflammatory; Interferons; Lead; Length of Stay; Mass Spectrum Analysis; Mediating; Modeling; Mucocutaneous Lymph Node Syndrome; Myocardial dysfunction; Onset of illness; Outcome; Pathology; Pathway interactions; Patients; Plasma; Population; Production; Proteins; Renin-Angiotensin System; Risk; Schools; Serologic tests; Serum; Structure of germinal center of lymph node; Syndrome; Testing; Up-Regulation; Viral Antibodies; Virus; acute infection; base; cohort; cytokine; genetic analysis; heart damage; heart function; immune activation; macrophage; metabolic profile; metabolomics; neutralizing antibody; neutrophil; pandemic disease; pediatric patients; receptor binding; response; risk variant; seropositive; young adult

Abstract This proposal seeks to test two hypotheses regarding the Multisystem Inflammatory Syndrome (MIS-C) recently identified in children and young adults infected with SARS-CoV-2. We hypothesize that there is a spectrum of disease from severe acute disease to MIS-C. Severe Cov acute disease is associated with low interferon production, poor control of virus and a germinal center derived antibody response to the virus leading to long term immunity while MIS- C is associated with high interferon, efficient control of virus, but an extrafollicular derived antibody response with poor long term immunity. We will test this hypothesis through a genetic analysis, analysis of serum cytokines and analysis of anti-viral antibodies. We also hypothesize that plasma metabolic profile of subjects with MIS-C will predict short term cardiac dysfunction and long term cardiac damage.

摘要 该提案旨在测试关于多系统炎症综合征的两个假设 （MIS-C）最近在感染SARS-CoV-2的儿童和年轻人中发现。我们 假设存在从严重急性疾病到MIS-C疾病谱。严重 Cov急性疾病与干扰素产生低，病毒控制差和 免疫中心产生的抗体反应，导致长期免疫，而MIS- C与高干扰素相关，有效控制病毒，但卵泡外衍生 长期免疫力差的抗体反应。我们将通过一个基因测试来验证这一假设。 分析、血清细胞因子分析和抗病毒抗体分析。我们还假设 MIS-C受试者的血浆代谢谱可预测短期心功能不全 以及长期的心脏损伤