Monkey Alcohol Tissue Research Resource (MATRR)

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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.