Lung Innate COVID-19 Defense Specific to Veterans Risk Characteristics

COVID-19现在是一场全球性大流行病，需要科学和医学界迅速采取协调一致的应对措施。 社区根据几个月前从最早受影响的国家获得的最新流行病学资料， SARS-CoV-2病毒的发病机制和COVID-19的临床结果在个体中要糟糕得多 有一定的预先存在的条件和那些先进的年龄。对退伍军人的健康至关重要， 确定哪些风险状况特别影响他们及其独特需求，并立即在 以便在这次和未来的病毒大流行期间加强临床预防护理。相比一般 公共，退伍军人人口的特点可以是年龄较大，吸烟导致预先存在 肺部疾病如慢性阻塞性肺病（COPD）和酒精使用障碍（AUD）。我们 关于这些特征如何影响SARS-CoV-2发病机制的知识是有限的。然而，结果来自 我们以前的VA支持的研究已经证明，老年和AUD与 纤毛功能障碍我们的研究结果还表明，AUD导致表面活性剂抗微生物作用降低。 表面活性剂蛋白D已被证明特异性结合并中和人表皮生长因子受体的刺突蛋白。 冠状病毒。我们推测，在粘液纤毛清除水平上改变先天性肺防御，抗- 微生物表面活性剂和病毒受体功能将对易感性和发病机制产生负面影响， SARS-CoV-2，尤其是退伍军人。我们的调查小组包括一个退伍军人事务部 研究职业科学家，在酒精对肺损伤和修复的影响方面拥有25年的经验， 弗吉尼亚州的医生兼科学家，他的专长是年龄对肺功能的影响，还有一位微生物学家， 已经有在BSL 3条件下处理SARS-CoV-2的经验。结合我国现有 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 在正常气道上皮细胞和肺巨噬细胞之间SARS-CoV-2感染反应中， 从患有COPD、患有AUD或老年的个体收集。我们将在这些群体中特别确定任何 纤毛搏动控制清除率、表面活性蛋白D表达/结构/功能的变化，以及已知的 SARS-CoV-2受体。这些研究将首次在这些高危人群中进行， 的人口。定义风险的形式将使临床医生能够做出明智的临床预防 照顾退伍军人的决定

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.