Development of lung T cell responses in infant respiratory immunity

婴儿呼吸道免疫中肺 T 细胞反应的发展

• 批准号: 10221314
• 负责人: Donna L. Farber
• 金额: $ 74.2万
• 依托单位: COLUMBIA UNIVERSITY HEALTH SCIENCES
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-12-03 至 2022-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10221314
• 关键词: 2019-nCoV; Acute; Adult; Adult Respiratory Distress Syndrome; Affect; Aneurysm; Antibodies; Antibody Response; Attenuated; Biological Assay; Blood specimen; Businesses; COVID-19; COVID-19 pandemic; COVID-19 patient; COVID-19 severity; COVID-19 vaccine; COVID-19/ARDS; Cardiac; Cardiogenic Shock; Cardiology; Cardiopulmonary; Cardiovascular system; Characteristics; Child; Childhood; Clinical; Clinical Data; Complication; Coronary; Coronary artery; Coughing; Critical Care; Data; Decision Making; Development; Disease; Echocardiography; Elderly; Enrollment; Epitopes; Fatigue; Ferritin; Fever; Fibrin fragment D; Flow Cytometry; Functional disorder; Future; Health; Hospitals; Immune; Immune response; Immunity; Immunoglobulin G; Immunologics; Immunologist; Incidence; Individual; Infant; Infection; Inflammation; Inflammatory; Interleukin-6; Learning; Life; Measurement; Mediating; Medical center; Medicine; Morbidity - disease rate; Mucocutaneous Lymph Node Syndrome; Multisystem Inflammatory Syndrome in Children; Myocardial dysfunction; Neighborhoods; New York; Nucleocapsid Proteins; Outcome; Patients; Pediatric cohort; Peptides; Population; Presbyterian Church; Prevention strategy; Prospective cohort study; Proteins; Reading; Recovery; Reporting; Research; Research Personnel; Respiratory Failure; Respiratory Tract Infections; Risk; SARS-CoV-2 antibody; SARS-CoV-2 infection; SARS-CoV-2 positive; Sampling; Schools; Shock; Symptoms; Syndrome; T cell response; T-Lymphocyte; Testing; Toxic Shock Syndrome; Vaccination; Vasculitis; Viral; Virus; Washington; adaptive immune response; age related; clinical care; cohort; community clinic; effector T cell; experience; high dimensionality; infection rate; insight; interdisciplinary approach; lung development; lung injury; mortality; neutralizing antibody; novel; novel coronavirus; pandemic disease; pediatric patients; pediatrician; prospective; respiratory; response; severe COVID-19; treatment strategy

PROJECT SUMMARY The emergence of SARS-CoV-2 has resulted in a worldwide pandemic. Infection with SARS-CoV-2 causes a spectrum of disease symptoms ranging from asymptomatic and mild/self-limited disease, to severe disease associated with significant lung damage and high levels of morbidity and mortality. As all individuals are immunologically naïve to this virus and there are currently no targeted treatments or vaccines against SARS- CoV-2, protection and recovery depend on our own immune responses and supportive clinical care. Initially, children experienced largely asymptomatic or mild disease with severe disease resulting in significant lung injury a rare occurrence. However, a new multisystem inflammatory disorder in children (MIS-C) related to SARS-CoV-2 has emerged as a late complication of infection. Children with MIS-C commonly present with cardiac dysfunction and shock, most closely resembling Kawasaki disease and toxic shock syndrome. Importantly, some children presenting with MIS-C have been reported to develop coronary artery aneurysms, a finding common to Kawasaki disease. The significant amount of mild/self-limited disease in children contrasted with the excessive inflammation associated with SARS-CoV-2 suggests distinct immune responses. Additionally, the long-term implications, particularly to the cardiovascular system, of early life infection with SARS-CoV-2 remain unknown. We hypothesize that these distinct clinical manifestations in children, including lack of symptomatic respiratory infection to SARS-Cov-2 is due to a robust and enhanced T cell response. The aims of this proposal are to 1) Establish pediatric patient cohorts for comparing outcomes and immune responses across the spectrum of pediatric COVID-19 disease, 2) Define the pediatric immune response to SARS-CoV-2 and how it differs across the clinical spectrum of disease, and 3) Define the incidence of and patient characteristics associated with sustained adverse cardiac outcomes for children with MIS-C and pediatric COVID-19. This project proposes to provide new insights into the pediatric immune and long-term complications of SARS-CoV-2 infection by employing a multi-disciplinary approach utilizing a team of investigators including immunologists, pediatricians, and pediatric subspecialists (cardiology/critical care medicine). These studies will provide invaluable insight that will help guide future decision making for treatment and preventative strategies for children.

项目摘要 SARS-COV-2的出现导致全球大流行。 SARS-COV-2感染引起 从渐近和轻度/自限性疾病到严重疾病的疾病症状范围 与大量肺损伤以及高水平的发病率和死亡率相关。所有个人都是 在免疫学上对这种病毒很幼稚，目前尚无针对SARS-的靶向治疗或疫苗 COV-2，保护和恢复取决于我们自己的免疫回报和支持性的临床护理。最初， 儿童经历了很大的无症状或轻度疾病，患有严重疾病，导致肺明显 受伤很少发生。但是，儿童的一种新的多系统炎症障碍（MIS-C） SARS-COV-2已成为感染的晚期并发症。 MIS-C通常出现的孩子 心脏功能障碍和休克，最类似于川崎疾病和有毒休克综合征。 重要的是，据报道，一些患有MIS-C的儿童会发展为冠状动脉动脉瘤， 发现川崎疾病常见。儿童中大量的轻度/自限性疾病形成鲜明对比 随着与SARS-COV-2相关的过量炎症表明了不同的免疫反应。 此外，长期影响，特别是对心血管系统的早期生命感染的影响 SARS-COV-2仍然未知。我们假设这些儿童中这些独特的临床表现，包括 缺乏对SARS-COV-2的症状呼吸道感染是由于T细胞反应强大而增强的。这 该提案的目的是1）建立儿科患者队列以比较结果和免疫 小儿共vid-19疾病的各种范围的反应，2）定义小儿免疫反应 SARS-COV-2及其在疾病的临床范围内的差异以及3）定义和 与MIS-C和MIS-C儿童持续不良心脏结局相关的患者特征和 小儿covid-19。该项目的提议旨在为小儿免疫和长期提供新的见解 SARS-COV-2感染的并发症通过采用多学科的方法利用一个团队 包括免疫学家，儿科医生和儿科专科医生在内的研究人员（心脏病学/重症监护 药品）。这些研究将提供宝贵的见解，以帮助指导未来的治疗决策 和儿童的预防策略。