GENOMIC APPROACHES TO UNDERSTAND DISEASE SUSCEPTIBILITY AND PATHOGENESIS OF SARS-COV-2

整体项目总结 2019年12月在中国首次发现的新型冠状病毒SARS-CoV-2现已蔓延 全球范围内。德克萨斯州休斯敦的德克萨斯医疗中心是美国第四大城市，也是 种族多样性，对大流行采取了积极的早期应对措施，主要侧重于急性护理。在 贝勒医学院，TMC-基因组传染病中心(TMC-GCID)计划成员 (https://gcid.research.bcm.edu/overview)正在利用现有基础设施，以及主动和 强大的样本收集流与临床和社区检测相联系，以确定SARS-CoV-2的特征 整个地区的毒力和易感性。本申请向TMC-GCID申请补充资金 帮助支持SARS-CoV-2社区范围的监测，完成病毒基因组测序，鼻咽部 微生物组分析和目标宿主遗传分析。本补充文件的主要目标是 通过基础和内科科学家组成的多学科综合团队的共同努力实现 有良好的合作记录，并且已经在实现TMC-GCID的主要目标。这个 我们GCID附录的总体目标是研究SARS-CoV-2感染的生物学，宿主和 与疾病相关的微生物遗传学，并满足社区需求，特别是在 服务不足的社区，通过以下目标：i)扩大业务应急用途 授权(EUA-)和IRB兼容的新冠肺炎qPCR筛查/监控计划，包括 在线登记和同意以及符合HIPAA标准的结果返回，ii)排序和分析 从TMC及其周围收集的SARS-CoV-2感染者的全长基因组 区域，三)确定可预测新冠肺炎疾病严重程度和/或 结果，四)根据病毒滴度、疾病严重程度和 新冠肺炎阳性患者的结局，包括人类白细胞抗原(HLA1)基因多态性， 血管紧张素转换酶2和自然杀伤细胞免疫球蛋白样受体 地区。本附录将利用尖端的高通量测序策略和 由TMC-GCID测序技术(ST)核心提供的技术，在生成发现、数据、 工具和试剂将被分析并通过 TMC-GCID数据管理分析和资源传播(DMARD)核心。结果将是一个 SARS-CoV-2感染宿主和微生物的综合遗传图谱将揭示病原体基因 与个体宿主反应表型相关的变体将告知精确医学基础 治疗和诊断，不仅针对SARS-CoV-2，而且针对我们已经面临的其他大流行威胁 深刻地改变了我们周围的世界。

OVERALL PROJECT SUMMARY The novel coronavirus, SARS-CoV-2, that was first detected in China in December 2019 has now spread globally. The Texas Medical Center in Houston, TX, the fourth largest city in the US, and among the top 10 in racial diversity, mounted an aggressive early response to the pandemic, primarily focused on acute care. Within Baylor College of Medicine, members of the TMC - Genomic Center for Infectious Disease (TMC-GCID) program (https://gcid.research.bcm.edu/overview) are leveraging existing infrastructure, together with an active and robust sample collection stream linked to both clinical and community testing, to characterize SARS-CoV-2 virulence and susceptibility across the region. This application requests supplemental funding to the TMC-GCID to help support SARS-CoV-2 community-wide surveillance, complete viral genome sequencing, nasopharyngeal microbiome profiling, and targeted host genetic analyses. The primary objective of this supplement will be achieved through the collaborative efforts of a multidisciplinary, integrated team of basic and physician scientists with a track-record of collaboration and who are already delivering on the primary goals of the TMC-GCID. The overall goals of our GCID supplement is to study the biology of SARS-CoV-2 infection, the host and microbial genetics associated with disease, and to address community needs, particularly in underserved communities, through the following aims: i) expand an operational Emergency Use Authorization- (EUA-) and IRB-compliant COVID-19 qPCR screening/surveillance program featuring online enrollment and consent as well as HIPAA-compliant return of results, ii) sequence and analyze full-length SARS-CoV-2 genomes from infected individuals collected from the TMC and surrounding area, iii) identify microbial co-colonization/co-infections that predict COVID-19 disease severity and/or outcome, iv) Characterize the host genetic variation with respect to viral titer, disease severity, and outcome in patients positive for COVID-19, including polymorphisms in human leukocyte antigen (HLA), angiotensin-converting enzyme 2 (ACE2), and natural killer cell immunoglobulin-like receptor (KIR) regions. This supplement will leverage the cutting edge, high-throughput sequencing strategies and technologies supplied by the TMC-GCID Sequencing Technology (ST) Core, in generating discoveries, data, tools, and reagents that will be analyzed and disseminated to the infectious disease community through the TMC-GCID Data Management Analysis and Resource Dissemination (DMARD) Core. The result will be a comprehensive genetic profiling of hosts and microbes in SARS-CoV-2 infection that will reveal pathogen genetic variants associated with individual host response phenotypes that will inform precision medicine-based therapeutics and diagnostics, not just for SARS-CoV-2, but for other pandemic threats that we have already observed to profoundly change the world around us.