Uncovering associations of variant infection with COVID-19 disease severity in children

揭示变异感染与儿童 COVID-19 疾病严重程度的关联

• 批准号: 10516696
• 负责人: Charles Yen Chiu
• 金额: $ 154.11万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
• 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 2023-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10516696
• 关键词: 2019-nCoV; Acute; Address; Archives; Artificial Intelligence; Biological Markers; Biometry; COVID-19; COVID-19 complications; COVID-19 patient; COVID-19 pneumonia; COVID-19 severity; California; Cessation of life; Child; Childhood; Clinical; Communities; DNA analysis; Data; Development; Diagnosis; Diagnostic; Disease; Disease Outcome; Enrollment; Genbank; Genome; Grant; Hospitalization; Hospitals; Individual; Infection; Inflammatory; Inflammatory Response; Knowledge; Laboratories; Los Angeles; Medical; Medicine; Metadata; Monitor; Multisystem Inflammatory Syndrome in Children; Mutation; Myocarditis; Outcome; Patients; Pattern; Pediatric Hospitals; Pediatric cohort; Pennsylvania; Population; Predisposition; Public Health; RNA; Research Infrastructure; Reverse Transcriptase Polymerase Chain Reaction; SARS-CoV-2 infection; SARS-CoV-2 variant; Sampling; San Francisco; Severities; Severity of illness; Single Nucleotide Polymorphism; Syndrome; System; Testing; Texas; Time; United States National Institutes of Health; Universities; Variant; Viral; Viral Genome; Viral Load result; Virus; Work; biobank; cell free DNA; clinically relevant; co-infection; cohort; college; diagnostic panel; disorder risk; genetic pedigree; genetic variant; genome sequencing; nasal swab; pandemic disease; parent grant; pediatric patients; predictive modeling; prospective; public repository; respiratory virus; response; severe COVID-19; transcriptome; whole genome

Project Abstract Under parent grant R61HD105618 (PI Chiu, University of California, San Francisco), we proposed to define panels of diagnostic and predictive host markers of COVID-19 in children, with a focus on severe clinical manifestations of disease, including COVID-19 associated pneumonia, myocarditis, and multisystem inflammatory syndrome in children (MIS-C). Our aims were to collect and biobank clinical samples from pediatric patients with COVID-19 and MIS-C, perform RNA transcriptome profiling and cell-free DNA analyses to identify host biomarkers, and generate predictive models of clinical severity and outcomes. Here we propose a supplemental project in response to the threat posed by newly emerging SARS-CoV-2 variants, such as Delta. We will perform SARS-CoV-2 viral whole-genome sequencing of >4,000 samples across 5 pediatric hospital systems and correlate variant identification with clinical and laboratory metadata. We aim to determine whether infection from specific variants is associated with more severe illness or complications of COVID-19 disease such as MIS-C. Uncovering potential differences in clinical severity due to infection from specific variants is critical to understanding surges in pediatric hospitalizations associated with SARS-CoV-2 and to informing development of host biomarkers for diagnosing and monitoring disease complications such as COVID-19 pneumonia, myocarditis, and MIS-C. .

项目摘要 在家长资助R61HD105618(皮丘，加州大学旧金山分校)下，我们建议 确定儿童新冠肺炎的诊断和预测宿主标志物小组，重点放在严重的临床 疾病表现，包括新冠肺炎相关性肺炎、心肌炎和多系统疾病 儿童炎性综合征(MIS-C)。我们的目标是收集和生物库临床样本 新冠肺炎和MISC的儿科患者进行了核糖体转录组分析和无细胞DNA分析 识别宿主生物标记物，并生成临床严重性和结果的预测模型。在这里，我们建议 一个补充项目，以应对新出现的SARS-CoV-2变种构成的威胁，例如 达美航空。我们将对5个儿科的4,000个样本进行SARS-CoV-2病毒全基因组测序 医院系统，并将变异识别与临床和实验室元数据相关联。我们的目标是确定 来自特定变异的感染是否与新冠肺炎更严重的疾病或并发症有关 疾病，如MIS-C。发现由特定来源的感染引起的临床严重程度的潜在差异 变异对于了解与SARS-CoV-2相关的儿科住院激增以及 为诊断和监测疾病并发症提供信息的宿主生物标志物的发展，如 新冠肺炎肺炎、心肌炎、心肌梗死。 。