BIOREPOSITORY OPTIMIZATION AND USE FOR ENDOTYPING CRITICALLY ILL SARS-COV-2 INFECTED PATIENTS

生物样本库优化和用于重症 SARS-COV-2 感染患者内型分析

基本信息

批准号：
10684890
负责人：
Leopoldo Nicolas Segal
金额：
$ 20.74万
依托单位：
NEW YORK UNIVERSITY SCHOOL OF MEDICINE
依托单位国家：
美国
项目类别：
财政年份：
2022
资助国家：
美国
起止时间：
2022-08-16 至 2024-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10684890
关键词：
2019-nCoV Acute Antibody Response Area Biological Response Modifiers Blood Blood specimen Bronchoalveolar Lavage Bronchoscopy COVID-19 COVID-19 pandemic COVID-19 patient COVID-19 severity Caring Cells Circulation Clinical Communities Credentialing Critical Care Critical Illness Disease Ensure Environment Etiology Event Evolution Funding Future Grant Health Healthcare Systems Human Immune Immune response Immunoglobulin G Individual Infrastructure Investigation Mediating Microbiology Molecular Molecular Profiling Nature New York New York City Outcome Pathway interactions Patients Peripheral Blood Mononuclear Cell Phase Physicians Population Process Protocols documentation Publications Publishing Reporting Research Resources SARS-CoV-2 infection Sampling Sampling Studies Secure Source Standardization Testing Time Trachea United States Viral Viremia Virus Replication aspirate bacteriome biobank clinical heterogeneity experience host-microbe interactions metabolome metabolomics microbial mortality mortality risk multiple omics novel novel marker pathogen prognostication respiratory microbiome response sample collection septic patients single-cell RNA sequencing trait transcriptome transcriptomics virome

项目摘要

Abstract. The New York City area has faced a surge of cases early on the COVID-19 pandemic in the United States leading to destabilization of multiple health care systems that could not keep up with the high demand for critical care use and mortality. The heterogenous evolution among critically ill COVID-19 patients, high mortality and prolonged ICU stay highlights the need to better understand individual’s endotype that could expose treatable traits among these septic patients. As the first set of cases arrived to NYU, we built a biorepository of samples from the lower airways and blood from these critically-ill SARS-CoV-2 infected patients. We have already explored the lower airway microbial environment including the virome, bacteriome and host immune response. In our recent report using cross sectional lower airway samples from 142 critically ill COVID-19 patients published in Nature Microbiology we identified microbial and host signatures associated with poor outcome, predominantly driven by poorly controlled viral replication, blunted anti-Spike/anti-RBD IgG response and distinct host transcriptomic profile. However, in order to understand the mechanism underlying this poor viral control we need to study samples at earlier time points and longitudinally. We are currently using these samples to characterize the longitudinal viral and host transcriptome dynamics. However, the critical molecular immune mediators need to be explored using metabolomic approaches while the distinct cellular immune responses may require single cell approaches. In this application we will use our existing biorepository and expand it with new cases to test the hypothesis that airway and systemic endotyping with novel scRNA sequencing and metabolomic approaches predicts poor outcome in critically ill SARS-CoV-2 patients. Thus, we propose to expand and optimize our biorepository of airway and systemic samples in critically ill SARS-CoV-2 patients (R21 phase) in order to perform scRNA sequencing and metabolomic approaches in order to endotype the airway and systemic environment to evaluate for associations with poor clinical outcome (R33 phase). To accomplished these aims we will use our expertise in the characterization of the lower airway microbiome (including the viral fraction) and the host immune profile. Therefore, this is an unprecedented opportunity to conduct the necessary exploratory investigations on paired lower airway and systemic samples from critically ill COVID-19 patients. Lay summary. Acute COVID-19 infection has had unprecedented effects on human health with critically ill patients suffering high critical care resources and mortality. In this project, we will use and expand our biorepository of lower airway and blood samples to explore novel ways to determine molecular signatures that can predict patients’ poor clinical outcomes.

抽象的。纽约市地区的案件早期面临统一的19日大流行的案件各州导致多个医疗保健系统的稳定，这些系统无法跟上高需求重症监护和死亡率。重症199例患者的异质进化，高死亡率长时间的ICU留下来强调需要更好地了解个人内型的需求这些化粪池患者中的可治疗特征。当第一个案件到达纽约州时，我们建立了一个生物库来自较低气道的样本和来自这些急需的SARS-COV-2感染患者的血液。我们有已经探索了下部气道微生物环境，包括病毒蛋白，细菌和宿主免疫回复。在我们最近使用横截面下部气道样品的报告中自然微生物学发表的患者我们确定了与差的微生物和宿主特征结果，主要是由控制不良的病毒复制驱动，钝性抗尖峰/抗RBD IgG响应和不同的主机转录组轮廓。但是，为了理解这种病毒性较差的机制控制我们需要在较早的时间点和纵向研究样品。我们目前正在使用这些样品表征纵向病毒和宿主转录组动力学。但是，临界分子免疫需要使用代谢组学方法来探索介体，而不同的细胞免疫反应可能需要单细胞方法。在此应用程序中，我们将使用我们现有的生物库并将其扩展案例测试以下假设，即新型SCRNA测序和代谢组学方法预测，患病的SARS-COV-2患者的预后不佳。那我们建议在重病SARS-COV-2患者中扩展和优化我们的气道和全身样品的生物验证（R21）阶段）为了执行SCRNA测序和代谢组方法，以内化气道和系统环境，以评估临床结果不佳的关联（R33期）。完成这些目标我们将使用我们的专业知识来表征下气道微生物组（包括病毒分数）和宿主免疫轮廓。因此，这是进行必要的前所未有的机会探索性投资对危重病患者的较低气道和全身样本进行了探索性投资。摘要摘要。急性共vid-19感染对人类健康产生了前所未有的影响，病重患有高重症监护资源和死亡率的患者。在这个项目中，我们将使用并扩展我们的下呼吸道和血液样本的生物座位，以探索新的方法来确定分子特征可以预测患者的临床结果不佳。