Lung Innate COVID-19 Defense Specific to Veterans Risk Characteristics

针对退伍军人风险特征的肺部先天性 COVID-19 防御

• 批准号: 10359086
• 负责人: Kristina L Bailey
• 金额: --
• 依托单位: OMAHA VA MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-01-01 至 2022-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10359086
• 关键词: 2019-nCoV; ACE2; Address; Affect; Age; Aging; Alcohol abuse; Alcohols; Alveolar Macrophages; Alveolus; Binding; COVID-19; COVID-19 mortality; COVID-19 pandemic; COVID-19 risk; Cells; Cessation of life; Characteristics; Chronic Obstructive Pulmonary Disease; Chronic lung disease; Cilia; Clinical; Collectins; Communities; Contracts; Coronavirus; Coronavirus Infections; Coronavirus spike protein; Country; Data; Defense Mechanisms; Defensins; Disease; Elderly; Enzymes; Epidemiology; Epithelial Cells; Functional disorder; Future; GRP78 gene; General Population; Health; Human; Immune; Impairment; Individual; Infection; Innate Immune System; Knowledge; Lead; Lung; Lung diseases; Medical; Modality; Mucociliary Clearance; Mucous body substance; Natural Immunity; Outcome; Patients; Persons; Physicians; Population; Predisposing Factor; Predisposition; Preventive care; Process; Proteins; Pulmonary Surfactant-Associated Protein D; Research; Research Personnel; Research Support; Risk; Risk Factors; Role; Route; SARS-CoV-2 infection; SARS-CoV-2 pathogenesis; Scientist; Site; Smoking; Structure; Symptoms; Testing; Time; Tissues; Veterans; Viral; Virus; Virus Diseases; Virus Receptors; Vulnerable Populations; Work; Writing; age effect; airway epithelium; alcohol misuse; alcohol use disorder; antimicrobial; base; biobank; career; cigarette smoking; experience; high risk; high risk population; human old age (65+); infection rate; injury and repair; lung injury; macrophage; military veteran; mortality; novel coronavirus; pandemic disease; particle; prevent; pulmonary function; receptor; receptor function; response; skills; surfactant; 2019-nCoV; ACE2; Address; Affect; Age; Aging; Alcohol abuse; Alcohols; Alveolar Macrophages; Alveolus; Binding; COVID-19; COVID-19 mortality; COVID-19 pandemic; COVID-19 risk; Cells; Cessation of life; Characteristics; Chronic Obstructive Pulmonary Disease; Chronic lung disease; Cilia; Clinical; Collectins; Communities; Contracts; Coronavirus; Coronavirus Infections; Coronavirus spike protein; Country; Data; Defense Mechanisms; Defensins; Disease; Elderly; Enzymes; Epidemiology; Epithelial Cells; Functional disorder; Future; GRP78 gene; General Population; Health; Human; Immune; Impairment; Individual; Infection; Innate Immune System; Knowledge; Lead; Lung; Lung diseases; Medical; Modality; Mucociliary Clearance; Mucous body substance; Natural Immunity; Outcome; Patients; Persons; Physicians; Population; Predisposing Factor; Predisposition; Preventive care; Process; Proteins; Pulmonary Surfactant-Associated Protein D; Research; Research Personnel; Research Support; Risk; Risk Factors; Role; Route; SARS-CoV-2 infection; SARS-CoV-2 pathogenesis; Scientist; Site; Smoking; Structure; Symptoms; Testing; Time; Tissues; Veterans; Viral; Virus; Virus Diseases; Virus Receptors; Vulnerable Populations; Work; Writing; age effect; airway epithelium; alcohol misuse; alcohol use disorder; antimicrobial; base; biobank; career; cigarette smoking; experience; high risk; high risk population; human old age (65+); infection rate; injury and repair; lung injury; macrophage; military veteran; mortality; novel coronavirus; pandemic disease; particle; prevent; pulmonary function; receptor; receptor function; response; skills; surfactant

COVID-19 is now a global pandemic requiring a rapid and concerted response from the scientific and medical community. Based upon recent epidemiology derived only months earlier from the earliest affected countries, the pathogenesis of the SARS-CoV-2 virus and clinical outcomes from COVID-19 are far worse in individuals with certain pre-existing conditions and those of advanced age. It is essential to the health of Veterans to fully define which at-risk conditions particularly impact them and their unique needs and to do so immediately in order to empower clinical preventive care during this and future viral pandemics. Compared to the general public, the Veterans population can be characterized by older age, cigarette smoking leading to pre-existing lung diseases such as chronic obstructive pulmonary disease (COPD), and alcohol use disorders (AUD). Our knowledge about how such characteristics impact SARS-CoV-2 pathogenesis is limited. However, results from our previous VA-supported research have already demonstrated that old age and AUD are associated with cilia dysfunction. Our results also demonstrate that AUD results in decreased surfactant anti-microbial action. Surfactant protein D has been documented to specifically bind to and neutralize the Spike protein of coronavirus. We hypothesize that altered innate lung defense at the level of mucociliary clearance, anti- microbial surfactants, and viral receptor function will negatively impact susceptibility and pathogenesis of SARS-CoV-2, placing Veterans particularly in harm’s way. Our assembled team of investigators include a VA Research Career Scientist with 25 years’ experience in the impact of alcohol on lung injury and repair, a physician-scientist at the VA whose expertise is on the impact of age in lung function, and a microbiologist who is already experienced in working with SARS-CoV-2 under BSL3 conditions. Combined with our existing biobank of human lung cells and tissues, we propose to address our hypothesis by identifying any differences in SARS-CoV-2 infection responses between normal airway epithelium and lung macrophages and those cells collected from individuals with COPD, with AUD, or of old age. We will specifically identify in these groups any changes in cilia beat controlling clearance, surfactant protein D expression/structure/function, and known SARS-CoV-2 receptors. Such studies will be performed for the first time in these high-risk groups common to the VA population. Defining the modalities of risk will empower clinicians to make informed clinical preventive care decisions for Veterans.

Covid-19现在是一个全球大流行，需要科学和医学的迅速和一致的反应 社区。基于最近几个月前从最早受影响的国家衍生的流行病学， SARS-COV-2病毒的发病机理和COVID-19的临床结果在个体中差得多 有某些先前存在的条件和高龄条件。对退伍军人的健康至关重要 定义哪种高危条件特别影响他们及其独特的需求，并立即这样做 为了在此期间和将来的病毒大流行过程中赋予临床预防保健能力。与一般相比 公众，退伍军人人口的特征是年龄较大，吸烟，导致先前存在 肺部疾病，例如慢性阻塞性肺疾病（COPD）和酒精使用障碍（AUD）。我们的 有关这种特征如何影响SARS-COV-2发病机理的知识受到限制。但是，结果 我们以前的VA支持研究已经证明，老年和AUD与 纤毛功能障碍。我们的结果还表明，AUD导致生存抗菌作用改善。 已经记录了表面活性剂蛋白D，以特异性结合并中和 新冠病毒。我们假设在粘膜清除，抗 - 微生物表面和病毒受体功能将对易感性和发病机理产生负面影响 SARS-COV-2，尤其是在伤害方面放置退伍军人。我们组建的调查人员团队包括VA 研究职业科学家在酒精对肺损伤和维修的影响方面拥有25年的经验，这是一个 VA的身体科学家，其专业知识对肺部功能的影响以及一名微生物学家的影响 在BSL3条件下与SARS-COV-2合作已经经验丰富。结合我们现有的 人类肺细胞和组织的生物库，我们建议通过识别任何差异来解决我们的假设 在正常气道上皮和肺巨噬细胞之间的SARS-COV-2感染反应中 从患有COPD，AUD或老年的人那里收集。我们将在这些小组中具体确定任何 纤毛搏动控制清除率，表面活性剂蛋白D表达/结构/功能的变化以及已知的 SARS-COV-2受体。这些研究将在这些共有的这些高风险组中首次进行 VA人口。定义风险的方式将使临床医生有能力进行知情的临床预防 对退伍军人的护理决定。