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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.

总结 SARS-CoV-2大流行需要迅速作出反应，以解决广泛的医疗和科学问题。这些问题旨在减轻对人口的伤害，减缓并最终消除这一流行病。了解当然，历史，和发病机制，将导致有效的治疗和疫苗，这是至关重要的回答几个基本的科学问题纵向：病毒，遗传，生态因素和共发病/共- 需要确定感染风险因素：1）有症状和无症状感染; 2）长期脱落; 3）急性和慢性后遗症。特别是，我们必须确定相关的减少病毒载量在疾病早期的上呼吸道，以及宿主病毒反应，定义后来的严重降低，呼吸道疾病和ARDS，其以细胞因子风暴为先导。我们假设病毒性（高病毒载量、特异性病毒毒力特征、呼吸道病毒合并感染和病毒组）、生态 (such微生物群落结构/功能）和宿主（局部粘膜免疫应答）因素将预测疾病结果和严重程度。以下是我们的具体目标，以解决我们的假设：目标1：确定SARS-CoV 2病毒载量的纵向动力学，以建立鼻病毒载量与病毒脱落与疾病严重程度相关。目的2：描述SARS-CoV 2感染如何改变鼻腔 2019冠状病毒病期间的微生物组组成、结构和继发性细菌感染。目标3：审查是否 SARS-CoV 2感染期间的鼻微生物组模式与局部免疫应答相关，细胞因子风暴总的来说，这项研究将确定SARS-CoV 2病毒动力学，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中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对SARS-CoV 2感染的影响以及对Covid-19结果的影响。

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）

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.