Functional Measures of Lung Health in Chronic Ethanol Drinking for Understanding SARS-CoV-2 Infection and Treatment

项目摘要 SARS-CoV-2是COVID-19的病原体，它导致了一场持续的大流行， 截至2020年6月11日，美国有115，000名感染者和115，000人死亡，病例仍在上升。类似于 由SARS和MERS冠状病毒引起的呼吸道疾病，COVID-19的特点是疲劳， 咳嗽、发热、咳痰、呼吸困难和急性呼吸窘迫综合征（ARDS）。ARDS是 过度肺部炎症导致液体和炎性细胞碎片积聚， 导致气体交换和氧气水平降低，最终导致多器官衰竭。领导 关于SARS-CoV-2发病机制的分子基础的假设是， 炎性细胞因子、趋化因子和可溶性介质导致使人衰弱的细胞因子风暴， 导致严重的肺组织损伤（3-6）。目前的研究表明，髓系细胞亚群在白血病的发生中起着重要作用。 发展的细胞因子风暴，但确切的作用，促炎肺泡单核细胞和 巨噬细胞尚未被彻底检查和动物或人类受试者研究。SARS-CoV-2 日常生活和社交环境的破坏导致酒类销售和消费增加， 饮料.由于长期大量饮酒会损害肺部健康和免疫力， 易受细菌和病毒肺部感染，是ARDS的危险因素。因此，慢性 大量饮酒可能会增加感染COVID-19的机会，并加剧疾病进程。 然而，没有在对照人群中进行的纵向研究，可以提供肺功能的精确测量， 功能与人类受试者的酒精消耗量的精确测量。在本提案中，我们将获得 肺功能试验（PFT），一种肺部感染（CT）和肺泡巨噬细胞的临床诊断， R24 AA 01943猴酒精组织研究资源（MATRR）。这一增加的能力将成为一种资源， 让调查人员了解 19 酒精消费和COVID之间潜在的复杂关系， 相关成果并加强国家对当前大流行的应对措施。

PROJECT SUMMARY SARS-CoV-2, the causative agent of COVID-19, is responsible for a continuing pandemic with over 2 million infected individuals and 115,000 deaths in the US as of June 11, 2020 with cases still rising. Similar to the respiratory diseases caused by the SARS and MERS coronaviruses, COVID-19 is characterized by fatigue, cough, fever, sputum production, dyspnea, and acute respiratory distress syndrome (ARDS). ARDS is the result of excessive lung inflammation causing the accumulation of fluid and inflammatory cell debris and leading to decreased gas exchange and oxygen levels, and eventual multi-organ failure. The leading hypothesis for the molecular basis of SARS-CoV-2 pathogenesis is that an aberrant induction of pro- inflammatory cytokines, chemokines and soluble mediators lead to a debilitating cytokine storm that in turn results in severe lung tissue damage (3-6). Current studies suggest a major role for myeloid cell subsets in the development of the cytokine storm, but the precise roles of pro-inflammatory alveolar monocytes and macrophages have not been thoroughly examined and animal or human subject studies. SARS-CoV-2 disruption to daily routines and social settings have led to increased sales and consumption of alcoholic beverages. As chronic heavy alcohol consumption compromises lung health and immunity leading to increased susceptibility to both bacterial and viral pulmonary infections, and is a risk factor for ARDS. Thus, chronic heavy alcohol drinking could increase the chances of COVID-19 infection and exacerbate the disease course. However, there are no longitudinal studies in controlled populations that provide both precise measures of lung function with exact measures of alcohol consumption in human subjects. In this proposal we will obtain a pulmonary functional test (PFT), a clinical diagnostic of lung infection (CT) and alveolar macrophages to the R24 AA01943 Monkey Alcohol Tissue Research Resource (MATRR). This added capacity will be a resource for investigators to understand 19 the potentially complex relationships between alcohol consumption and COVID- related-outcomes and to enhance the nation's response to the current pandemic.