Integrated Metagenomic and Metatranscriptomic Characterization of Inflammatory Chronic Rhinosinusitis Endotypes

炎症性慢性鼻窦炎内型的综合宏基因组学和宏转录组学特征

基本信息

批准号：
10265625
负责人：
Suman Ranjan Das
金额：
$ 15.3万
依托单位：
VANDERBILT UNIVERSITY MEDICAL CENTER
依托单位国家：
美国
项目类别：
财政年份：
2020
资助国家：
美国
起止时间：
2020-06-30 至 2021-12-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10265625
关键词：
Adaptive Immune System Affect Allergic Disease Asthma Bacteria Bacterial Genes Bioinformatics Biological Markers Chronic Clinical Clinical Research Cluster Analysis Communities Complement Complex Data Data Analyses Development Diagnostic Direct Costs Disease Ecology Enrollment Epithelial Etiology Evaluation Functional disorder Gene Expression Genes Genetic Transcription Genomics Goals Grant Healthcare Homeostasis Immune Immunophenotyping Inflammation Inflammatory Intervention Lead Link Metabolism Metagenomics Microbe Mucositis Mucous Membrane Mucous body substance Pathway interactions Patients Phase Phenotype Population Population Control Prevalence Quality of life Research Research Personnel Resources Sampling Severity of illness Sinus Standardization Structure Syndrome Taxonomy Techniques Testing Time Tissues Transcript United States National Institutes of Health Variant bacterial community base chronic inflammatory disease chronic rhinosinusitis clinically relevant cohort cytokine design genomic data host microbiome immune function insight interest metagenomic sequencing metatranscriptomics microbial microbial colonization microbial community microbiota multidisciplinary multiple omics nasal microbiome novel physical conditioning prospective transcriptome transcriptomics working group

项目摘要

SUMMARY The SARS-CoV-2 pandemic demands a swift response to address a broad range of medical and scientific questions to mitigate harm to populations and slow and eventually eliminate the epidemic. To understand the course, history, and pathogenesis that will lead to effective therapies and vaccines it is critical to answer several fundamental scientific questions longitudinally: Viral, genetic, ecological factors and co-morbidity/co- infections risk factors need to be identified for 1) symptomatic and asymptomatic infection; 2) prolonged shedding; and 3) acute and chronic sequelae. In particular we must define correlates of reduced viral load in upper airways early in disease, and the host-viral response that defines later severe lower respiratory disease and ARDS that is prefaced by cytokine storm. We hypothesize that a combination of viral (high viral load, specific viral signature of virulence, respiratory viral co-infection and virome), ecological (such as, microbiome community structure/function) and host (local mucosal immune response) factors will predict disease outcomes and severity. Below are our specific aims to address our hypothesis: Aim 1: Determine longitudinal kinetics of SARS-CoV2 viral load to establish association between nasal viral load and viral shedding with disease severity. Aim 2: Characterize how SARS-CoV2 infection changes nasal microbiome composition, structure and secondary bacterial infection during Covid-19. Aim 3: To examine if nasal microbiome patterns during SARS-CoV2 infection are associated with local immune responses and cytokine storm. Collectively, this study will identify determinants of SARS-CoV2 viral kinetics, persistence, virus-host and microbiome interactions. Specifically, our proposal will advance our understanding of the role of the upper airway microbiome in Covid-19 and establish its role in programming of the local immune response upon SARS-CoV2 infection and effects on Covid-19 outcomes.

概括 SARS-COV-2大流行要求快速回应以解决广泛的医学和科学问题质疑减轻人口的危害并缓慢并最终消除流行病的问题。理解病史，历史和发病机理将导致有效的疗法和疫苗纵向纵向的几个基本科学问题：病毒，遗传，生态因素和合并症/共同疾病需要确定感染风险因素1）有症状和无症状感染； 2）长时间脱落； 3）急性和慢性后遗症。特别是我们必须定义降低病毒负荷的相关性在疾病早期的上呼吸道和宿主病毒反应后来定义了严重的下部呼吸道疾病和ARD由细胞因子风暴所备。我们假设是病毒（高病毒载荷，毒力的特异性病毒特征，呼吸道病毒共感染和病毒蛋白），生态（例如，微生物组社区的结构/功能）和宿主（局部粘膜免疫反应）的因素将预测疾病的结果和严重程度。以下是我们解决我们的假设的具体目的：目标1：确定SARS-COV2病毒负荷的纵向动力学，以在鼻病毒载量与病毒性疾病严重程度。 AIM 2：表征SARS-COV2感染如何改变鼻腔在COVID-19期间，微生物组组成，结构和二次细菌感染。目标3：检查是否 SARS-COV2感染期间的鼻微生物组模式与局部免疫反应和细胞因子风暴。总的来说，这项研究将确定SARS-COV2病毒动力学的决定因素，持久性，病毒宿主和微生物组相互作用。具体而言，我们的建议将促进我们对 Covid-19的上呼吸道微生物组，并确定其在局部免疫反应编程中的作用在SARS-COV2感染和对COVID-19结果的影响后。

项目成果

期刊论文数量（6）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Olfactory training: what is the evidence?

DOI：
10.1002/alr.22681
发表时间：
2020-11
期刊：
International forum of allergy & rhinology
影响因子：
6.4
作者：
Turner JH
通讯作者：
Turner JH

Interim analysis of an open-label randomized controlled trial evaluating nasal irrigations in non-hospitalized patients with coronavirus disease 2019.

DOI：
10.1002/alr.22703
发表时间：
2020-12
期刊：
International forum of allergy & rhinology
影响因子：
6.4
作者：
Kimura KS;Freeman MH;Wessinger BC;Gupta V;Sheng Q;Huang LC;Von Wahlde K;Das SR;Chowdhury NI;Turner JH
通讯作者：
Turner JH

Current insight into treatment of chronic rhinosinusitis: Phenotypes, endotypes, and implications for targeted therapeutics.