Identifying biomarker signatures of prognostic value for Multisystem Inflammatory Syndrome in Children (MIS-C)

识别儿童多系统炎症综合征 (MIS-C) 预后价值的生物标志物特征

• 批准号: 10320491
• 负责人: MICHAEL A LYNES
• 金额: $ 80.71万
• 依托单位: CONNECTICUT CHILDREN'S MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-01-01 至 2022-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10320491
• 关键词: 2019-nCoV; Acute Renal Failure with Renal Papillary Necrosis; Acute Respiratory Distress Syndrome; Address; Adipose tissue; Adolescent; Adult; Algorithms; Asthma; Attention; Biological; Biological Markers; Biometry; Biosensor; Black American; Blood; Blood Vessels; COVID-19; COVID-19 diagnosis; COVID-19 outbreak; COVID-19 patient; COVID-19 severity; Cardiac; Centers for Disease Control and Prevention (U.S.); Child; Childhood; Clinical; Collaborations; Collection; Colombia; Coupled; Detection; Diagnostic; Disease; Elderly; Enrollment; Environmental Exposure; Epidemiology; Epigenetic Process; Europe; Exhibits; Flow Cytometry; Fluorescence; Genetic; Gut Mucosa; Hispanic Americans; Immune; Immune response; Immunologics; Infection; Inflammatory; Intervention Studies; Laboratories; Machine Learning; Mechanical ventilation; Mind; Molecular; Morbidity - disease rate; Mucocutaneous Lymph Node Syndrome; Multisystem Inflammatory Syndrome in Children; Native Americans; Neurosecretory Systems; Obesity; Outcome; Patient-Focused Outcomes; Patients; Population; RADx; Reporting; Respiratory distress; Risk; SARS-CoV-2 exposure; SARS-CoV-2 infection; Saliva; Sampling; Severity of illness; Symptoms; Syndrome; Techniques; Technology; Testing; Thrombosis; Time; United States; United States National Institutes of Health; Viral Pneumonia; Virus; acute infection; arm; biobank; biomarker discovery; biomarker signature; biosignature; care outcomes; cerebrovascular; clinically relevant; cohort; cost; deep learning; diagnostic algorithm; diagnostic value; fight against; gut-brain axis; instrument; microbiome analysis; minority children; mortality; pediatric patients; plasmonics; point of care testing; potential biomarker; prognostic; prognostic algorithm; prognostic value; programs; response; risk stratification; severe COVID-19; treatment strategy; young adult

PROJECT SUMMARY / ABSTRACT In adults, SARS-CoV-2 infection exhibits a wide range of clinical outcomes, from asymptomatic and mild disease to severe viral pneumonia, respiratory distress, acute kidney injury, thrombotic disorders, and serious cardiac, cerebrovascular and vascular complications. Severe infection can also occur both in children and young adults (< 21), and a significant proportion of children admitted with Covid-19 require ICU support, frequently including mechanical ventilation. In addition, children and adolescents with initially asymptomatic SARS-CoV-2 infection have presented with a rare, but very severe multisystem inflammatory syndrome (MIS-C). Epidemiologic, clinical and laboratory predictors of progression towards severe forms of acute infection with SARS-CoV-2 and MIS-C are thus urgently needed in the fight against Covid-19 in this population. As defined in the NIH Rapid Acceleration of Diagnostics (RADx) program, biomarker discovery can enable risk stratification and guide interventional studies to target Covid-19 patients at enhanced risk of developing complications and/or severe disease. To target this discovery initiative, herein we will use a battery of biological, immunological and molecular tests, including Grating-Coupled Fluorescence Plasmonic (GCFP) and advanced flow cytometry, to study children and young adults (<21 years) with mild, moderate or severe SARS-CoV-2 infection. GCFP allows the use of disposable biosensor chips that can be mass-produced at low cost and spotted in microarray format to greatly increase multiplexing capabilities. In addition, we will use a similar biomarker approach for rapid differentiation of patients with MIS-C versus other pediatric infectious or inflammatory conditions where the clinical presentation resembles MIS-C, most importantly Kawasaki disease. A child’s biologic and immunologic response to SARS-CoV-2 exposure is likely influenced by a variety of factors, including genetics, epigenetics and products of the mucosa/gut-brain axis, adipose tissue and neuroendocrine immune network, and further modulated by environmental exposures. With these factors in mind, we hypothesize that a child’s biomarker profile in response to SARS-CoV-2 infection enables a timely and accurate prediction of severity of Covid-19 and diagnosis of MIS-C, and will help guide treatment strategies, and predict patient outcomes. To test this hypothesis, we will use a non-traditional diagnostic and comprehensive biomarker discovery to characterize the clinical and laboratory spectrum of children and adolescents with mild, moderate and severe SARS-CoV-2 infection, as well as MIS-C. We will then validate our newly developed diagnostic and prognostic algorithm to distinguish MIS-C from other inflammatory disorders with overlapping clinical manifestations, including Kawasaki disease, and predict the longitudinal risk of complications.

项目摘要 /摘要 在成年人中，SARS-COV-2感染表现出广泛的临床结果，来自不对称和轻度疾病 严重的病毒性肺炎，呼吸窘迫，急性肾脏损伤，血栓性疾病和严重的心脏 脑血管和血管并发症。儿童和年轻人也可能发生严重的感染 （<21），很大一部分被COVID-19的儿童需要ICU支持，经常包括 机械通气。此外，最初具有不对称SARS-COV-2感染的儿童和青少年 已经出现了一种罕见但非常严重的多系统炎症综合征（MIS-C）。流行病学，临床 以及通过SARS-COV-2和MIS-C进行严重急性感染的实验室预测指标 因此，在这一人群中，在与Covid-19的斗争中迫切需要。正如NIH快速中的定义 诊断加速度（RADX）计划，生物标志物发现可以实现风险分层和指南 介入的研究以靶向共同19例患者，以增强并发症和/或严重的风险 疾病。为了针对这一发现倡议，我们将使用一系列生物学，免疫和分子 测试，包括光栅耦合荧光等离子（GCFP）和晚期流式细胞仪 患有轻度，中或重度SARS-COV-2感染的儿童和年轻人（<21岁）。 GCFP允许 使用一次性生物传感器芯片可以以低成本大量生产并以微阵列格式发现 大大增加了多路复用功能。此外，我们将使用类似的生物标志物方法进行快速 MIS-C患者与其他儿科感染或炎症状况的分化 临床表现类似于MIS-C，最重要的是川崎病。孩子的生物学和免疫学 对SARS-COV-2暴露的反应可能受到多种因素的影响，包括遗传学，表观遗传学 以及粘膜/肠脑轴，脂肪组织和神经内分泌免疫网络的产物以及进一步 由环境暴露调节。考虑到这些因素，我们假设孩子的生物标志物 响应SARS-COV-2感染的曲线可以及时准确预测Covid-19 和MIS-C的诊断，并将有助于指导治疗策略，并预测患者的预后。测试这个 假设，我们将使用非传统的诊断和全面的生物标志物发现来表征 轻度，中度和重度SARS-COV-2的儿童和青少年的临床和实验室光谱 感染以及MIS-C。然后，我们将验证我们新开发的诊断和预后算法 将MIS-C与其他具有重叠临床表现的炎症性疾病区分开来，包括川崎 疾病，并预测并发症的纵向风险。