Diagnosing and predicting risk in children with SARS-CoV-2- related illness

诊断和预测患有 SARS-CoV-2 相关疾病的儿童的风险

基本信息

批准号：
10732857
负责人：
JANE C BURNS
金额：
$ 127.5万
依托单位：
UNIVERSITY OF CALIFORNIA, SAN DIEGO
依托单位国家：
美国
项目类别：
财政年份：
2021
资助国家：
美国
起止时间：
2021-01-01 至 2024-11-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10732857
关键词：
2019-nCoV Acute Address Adult Age Months Antibodies Antibody Repertoire Antibody Response Antibody-Dependent Enhancement Antigens Aptamer Technology Bioinformatics Biology Burn injury COVID-19 COVID-19 pandemic COVID-19 patient California Cardiogenic Shock Case Study Child Childhood Clinical Clinical Data Clinical Research Collaborations Communicable Diseases Coronavirus Country Coupled Critical Illness Data Data Coordinating Center Data Set Deposition Detection Development Diagnosis Diagnostic Diagnostic tests Disease Disease Progression Fever Funding Gene Expression Profiling Immune response Immunity Industrialization Infant Infection Inflammatory Institutional Review Boards Lateral Link Liquid Chromatography London Measures Metadata Molecular Morbidity - disease rate Mucocutaneous Lymph Node Syndrome Multisystem Inflammatory Syndrome in Children Pathogenesis Patient Recruitments Patients Pattern Peptides Performance Phase Plasma Productivity Proteins Proteomics RADx Radical RNA Research Resources SARS-CoV-2 antibody SARS-CoV-2 exposure SARS-CoV-2 infection Sampling Serum Services Severities Severity of illness Shapes Site System Testing Transcript Universities Validation Whole Blood Work aptamer clinical predictors cohort college data sharing diagnostic signature diagnostic tool human coronavirus inflammatory marker machine learning method pediatrician post SARS-CoV-2 infection predictive signature prognostic tool programs progression risk prospective prototype rapid diagnosis response risk prediction severe COVID-19 tandem mass spectrometry testing services tool transcriptome sequencing transcriptomics two-dimensional vaccine development

项目摘要

In the wake of COVID-19 pandemic, Multisystem Inflammatory Syndrome in Children (MIS-C) has evolved as a new threat to children exposed to SARS-CoV-2. The emergence of MIS-C is so new and so rapidly evolving that there are currently no diagnostic tests to identify these patients nor are there tools to predict disease progression. Through established, funded, multi-center consortia in the U.S. (CHARMS: Characterization of MIS-C and its Relationship to Kawasaki Disease funded by PCORI) and the UK (DIAMONDS), we will collect clinical data and samples to support the proposed studies. First, we will generate transcript, protein and antibody datasets from children with COVID-19, MIS-C, and with other febrile illnesses. Next, we will use these data to devise tests to distinguish children at risk of progression to severe COVID-19 or MIS-C and diagnostic tests to distinguish these conditions from other causes of fever in children. Continuing our established collaboration with Columbia University, we will define the antibody repertoire against all known human coronaviruses and determine how pre-existing antibody to other coronaviruses may shape the immune response in acute SARS-CoV-2 infection and MIS-C. The first two years (R61) will build on the expertise of the assembled teams to discover unique proteomic and transcriptomic patterns in MIS-C and SARS-CoV-2- infected patients and relate clinical parameters to the antibody response to coronaviral antigens profiled on peptide arrays. This work will leverage already banked plasma, serum, and RNA samples from children with COVID-19, MIS-C, Kawasaki disease and other inflammatory conditions. Rigorous Go/NoGo criteria have been established and will determine progression to the R33 phase. The final two years (R33) will focus on platform development and multicenter and bi-national test validation to diagnose and predict severity in children with SARS-CoV-2 infection or MIS-C based on aptamer technology, lateral-flow protein detection, point-of-service RNA or antibody profiling with commercial partners. De-identified clinical and molecular data will be deposited in the RADx-rad hub to facilitate data sharing. Many potential hurdles in this type of research have already been overcome: a) IRB-approved patient recruitment for data and samples is on-going, b) clinical samples have been banked, c) strong preliminary data has been generated on RNAseq, aptamer proteomics, and coronaviral antibody responses, and d) the teams have a strong track record of previous collaboration and productivity. The synergistic expertise of these investigative teams in this multi-center proposal provides a unique opportunity to create diagnostic and prognostic tools for children suffering from the spectrum of SARS- CoV-2 illnesses. 1

在 COVID-19 大流行之后，儿童多系统炎症综合征 (MIS-C) 已发展成为一种暴露于 SARS-CoV-2 的儿童面临新的威胁。 MIS-C 的出现是如此新颖且发展如此迅速目前没有诊断测试来识别这些患者，也没有工具来预测疾病进展。通过在美国建立的、资助的、多中心的财团（CHARMS：特征 MIS-C 及其与川崎病的关系由 PCORI）和英国（DIAMONDS）资助，我们将收集支持拟议研究的临床数据和样本。首先，我们将生成转录本、蛋白质和来自患有 COVID-19、MIS-C 和其他发热性疾病的儿童的抗体数据集。接下来我们将使用这些数据设计测试以区分有进展为严重 COVID-19 或 MIS-C 风险的儿童和诊断进行测试以区分这些情况与儿童发烧的其他原因。继续我们既定的与哥伦比亚大学合作，我们将定义针对所有已知人类的抗体库冠状病毒并确定针对其他冠状病毒的现有抗体如何影响免疫急性 SARS-CoV-2 感染和 MIS-C 的反应。头两年（R61）将建立在专业知识的基础上组建团队以发现 MIS-C 和 SARS-CoV-2 中独特的蛋白质组和转录组模式感染患者并将临床参数与对冠状病毒抗原的抗体反应联系起来肽阵列。这项工作将利用已经储存的患有以下疾病的儿童的血浆、血清和 RNA 样本 COVID-19、MIS-C、川崎病和其他炎症性疾病。严格的 Go/NoGo 标准已建立并将确定 R33 阶段的进展。最后两年（R33）将重点关注平台开发和多中心和两国测试验证，以诊断和预测严重程度基于适体技术、侧流蛋白检测、SARS-CoV-2感染或MIS-C儿童与商业合作伙伴一起进行服务点 RNA 或抗体分析。去识别的临床和分子数据将存放在 RADx-rad 中心以方便数据共享。此类研究存在许多潜在障碍已经克服了：a) IRB 批准的患者数据和样本招募正在进行中，b) 临床样本已入库，c) 已生成有关 RNAseq、适体蛋白质组学的强有力的初步数据，和冠状病毒抗体反应，并且 d) 团队在之前的合作和生产率。这些研究团队在这个多中心提案中的协同专业知识提供了为患有 SARS 谱系的儿童创建诊断和预后工具的独特机会 CoV-2 疾病。 1