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

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 现在是一种全球大流行病，需要科学和医学界做出快速、一致的反应 根据仅几个月前从最早受影响的国家得出的最新流行病学数据， SARS-CoV-2 病毒的发病机制和 COVID-19 的临床结果在个体中要差得多 患有某些已有疾病和高龄的人，充分了解退伍军人的健康至关重要。 确定哪些高风险状况对他们及其独特需求特别影响，并立即这样做 与一般情况相比，在这次和未来的病毒大流行期间加强临床预防护理。 对于公众来说，退伍军人群体的特点是年龄较大、吸烟导致预先存在的 肺部疾病，例如慢性阻塞性肺病（COPD）和酒精使用障碍（AUD）。 然而，关于这些特征如何影响 SARS-CoV-2 发病机制的知识还很有限。 我们之前 VA 支持的研究已经证明，老年和 AUD 与 我们的结果还表明，AUD 会导致表面活性剂的抗菌作用降低。 表面活性剂蛋白 D 已被证明可以特异性结合并中和刺突蛋白 我们遭受了冠状病毒在粘液纤毛清除水平、抗病毒水平上的先天性肺部防御能力的改变。 微生物表面活性剂和病毒受体功能将对病毒的易感性和发病机制产生负面影响 SARS-CoV-2，使退伍军人尤其受到伤害。我们组建的调查团队中包括退伍军人管理局。 职业科学家，在酒精对肺损伤和修复的影响方面拥有 25 年经验， 退伍军人管理局的医师科学家，其专业知识是年龄对肺功能的影响，以及微生物学家 结合我们现有的条件，在 BSL3 条件下处理 SARS-CoV-2 已有经验。 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 正常气道上皮和肺巨噬细胞以及这些细胞之间的 SARS-CoV-2 感染反应 从患有慢性阻塞性肺病 (COPD)、澳元 (AUD) 或老年患者的个人中收集的数据，我们将在这些群体中特别识别出任何人。 纤毛跳动控制清除、表面活性剂蛋白 D 表达/结构/功能的变化，以及已知的 此类研究将首次在这些常见的高危人群中进行。 定义风险模式将有助于制定明智的临床预防措施。 退伍军人的护理决定。

项目成果

Aldehyde Trapping by ADX-102 Is Protective against Cigarette Smoke and Alcohol Mediated Lung Cell Injury.

• DOI: 10.3390/biom12030393
• 发表时间: 2022-03-02
• 期刊: Biomolecules
• 影响因子: 5.5
• 作者: Ochoa CA;Nissen CG;Mosley DD;Bauer CD;Jordan DL;Bailey KL;Wyatt TA
• 通讯作者: Wyatt TA

Synergistic Detrimental Effects of Cigarette Smoke, Alcohol, and SARS-CoV-2 in COPD Bronchial Epithelial Cells.

• DOI: 10.3390/pathogens12030498
• 发表时间: 2023-03-22
• 期刊: Pathogens (Basel, Switzerland)
• 作者: Muralidharan A;Bauer CD;Katafiasz DM;Strah HM;Siddique A;Reid SP;Bailey KL;Wyatt TA
• 通讯作者: Wyatt TA