Immune mediated lung injury in COVID-19

COVID-19 中免疫介导的肺损伤

基本信息

批准号：
10367945
负责人：
Jane C Deng
金额：
--
依托单位：
VETERANS HEALTH ADMINISTRATION
依托单位国家：
美国
项目类别：
财政年份：
2021
资助国家：
美国
起止时间：
2021-04-01 至 2023-03-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10367945
关键词：
2019-nCoV Acute Acute Lung Injury Acute Respiratory Distress Syndrome Acute respiratory infection Age Animal Model Apoptosis Bacterial Pneumonia COVID-19 COVID-19 pandemic Cardiopulmonary Cell Death Cells Cessation of life Chronic Coculture Techniques Collaborations Coronavirus Coronavirus Infections Data Development Disease Elderly Epithelial Cells Equilibrium Exposure to Failure Funding Grant Health Histones Host Defense Human Immune Immune response Immunology Immunotherapy Impairment In Vitro Infection Inflammation Inflammation Mediators Inflammatory Response International Knowledge Lead Leukocytes Literature Lung Lung infections Mechanical ventilation Mediating Mediator of activation protein Medical Modeling Morbidity - disease rate Mouse Strains Multiple Organ Failure Murine hepatitis virus Mus Natural Killer Cells Oxygen Pathogenesis Pathogenicity Pathology Patients Peptides Play Population Positioning Attribute Public Health Pulmonary Pathology Reporting Research Research Proposals Resolution Risk Risk Factors Role SARS-CoV-2 immunity SARS-CoV-2 infection Severe Acute Respiratory Syndrome Testing Veterans Viral Virus Virus Diseases Virus Replication Virus Shedding aging population antimicrobial antiviral immunity base behavioral phenotyping comorbidity cytotoxicity design extracellular fighting global health improved in vivo influenza pneumonia insight lung development lung injury male military veteran mortality neutrophil novel novel therapeutics pathogen patient population preservation prevent recruit repaired response severe COVID-19

项目摘要

SARS-CoV-2 and the disease it causes (COVID-19) has emerged as a major global public health threat in the span of a few months. In particular, SARS-CoV-2 adds to the present number of acute respiratory infections, including influenza and bacterial pneumonia, which are endangering the health of our veterans and aging population. In particular, severe COVID-19 disease is characterized by severe lung injury, which results in severely impaired oxygen delivery and ultimately multiple organ failure and death. Our ongoing research has focused on a population of white blood cells called neutrophils, which are the most abundant white blood cell in our body and which have been shown to be a pivotal immune cell that contributes greatly to lung injury. However, our current medical knowledge is inadequate for understanding what neutrophils do in the context of viral infection. Although neutrophils are critical for eliminating many types of infections, they are believed to be a major contributor to the development of lung injury, and how to balance their beneficial activities with their harmful functions is poorly understood. Therefore, a better understanding of how neutrophils behavior and phenotype are altered during severe SARS-CoV-2 and other viral infections would aid in developing novel therapies to improve their antimicrobial functions, while limiting their injurious effects. The research we propose in this grant will examine how well neutrophils eliminate SARS-CoV-2 viruses, or if they are an excessively activated population of immune cells recruited to the lung whose harmful activities outweighs their benefits. We also will test an exciting new treatment approach developed by our collaborator at UCLA to see if this can block the damaging effects of neutrophils on lung cells, while blocking viral replication. The results of this 2-year project will provide insights into the beneficial versus harmful contributions of neutrophils in the development of severe COVID-19 disease, and potentially identify new therapies to benefit veterans and other vulnerable patients.

SARS-CoV-2 及其引起的疾病 (COVID-19) 已成为全球主要公共卫生问题几个月内的健康威胁。特别是，SARS-CoV-2 增加了目前的急性呼吸道感染的数量，包括流感和细菌性肺炎，危及我们退伍军人和老龄化人口的健康。特别是严重的 COVID-19 该疾病的特点是严重的肺损伤，导致氧气严重受损分娩并最终导致多器官衰竭和死亡。我们正在进行的研究重点是称为中性粒细胞的白细胞群，是最丰富的白细胞在我们体内，它已被证明是一种关键的免疫细胞，对肺损伤。然而，我们现有的医学知识还不足以理解中性粒细胞在病毒感染的情况下会起作用。尽管中性粒细胞对于消除许多类型的感染，它们被认为是肺部发育的主要贡献者伤害，以及如何平衡其有益活动与有害功能还很薄弱明白了。因此，更好地了解中性粒细胞的行为和表型是如何发生的在严重的 SARS-CoV-2 和其他病毒感染期间发生的改变将有助于开发新的改善其抗菌功能，同时限制其有害作用的疗法。这我们在这笔赠款中提出的研究将检查中性粒细胞消除 SARS-CoV-2 的效果病毒，或者它们是招募到肺部的过度激活的免疫细胞群其有害活动大于其益处。我们还将测试一种令人兴奋的新疗法我们在加州大学洛杉矶分校的合作者开发的方法，看看这是否可以阻止破坏性影响中性粒细胞作用于肺细胞，同时阻止病毒复制。这个为期两年的项目的成果将提供有关中性粒细胞在体内的有益与有害贡献的见解严重的 COVID-19 疾病的发展，并可能找到有益的新疗法退伍军人和其他弱势患者。