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

项目摘要 根据父母资助R61 HD 105618（加州大学旧金山弗朗西斯科PI Chiu），我们提议 定义儿童COVID-19的诊断和预测宿主标志物组，重点关注严重的临床 疾病的表现，包括COVID-19相关肺炎，心肌炎和多系统 儿童炎症综合征（MIS-C）。我们的目标是收集和生物库临床样本， 儿童COVID-19和MIS-C患者，进行RNA转录组分析和游离DNA分析 以鉴定宿主生物标志物，并生成临床严重程度和结果的预测模型。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，如 δ的我们将对来自5个儿科的超过4，000份样本进行SARS-CoV-2病毒全基因组测序。 医院系统以及将变体识别与临床和实验室元数据相关联。我们的目标是确定 特定变异体感染是否与COVID-19的更严重疾病或并发症相关 疾病，如C。发现由于特定感染引起的临床严重程度的潜在差异 变异对于理解与SARS-CoV-2相关的儿科住院率激增以及 为开发用于诊断和监测疾病并发症的宿主生物标志物提供信息， 新冠肺炎、心肌炎和MIS-C。 .

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. .