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

PROJECT Summary: SARS-CoV-2, the causative agent of COVID-19, is responsible for a continuing pandemic with over 2 millioninfected individuals and 115,000 deaths in the US as of June 11, 2020 with cases still rising. Similar to therespiratory 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 theresult of excessive lung inflammation causing the accumulation of fluid and inflammatory cell debris andleading to decreased gas exchange and oxygen levels, and eventual multi-organ failure. The leadinghypothesis 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 turnresults in severe lung tissue damage (3-6). Current studies suggest a major role for myeloid cell subsets in thedevelopment of the cytokine storm, but the precise roles of pro-inflammatory alveolar monocytes andmacrophages have not been thoroughly examined and animal or human subject studies. SARS-CoV-2disruption to daily routines and social settings have led to increased sales and consumption of alcoholicbeverages. As chronic heavy alcohol consumption compromises lung health and immunity leading to increasedsusceptibility to both bacterial and viral pulmonary infections, and is a risk factor for ARDS. Thus, chronicheavy 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 lungfunction with exact measures of alcohol consumption in human subjects. In this proposal we will obtain apulmonary functional test (PFT), a clinical diagnostic of lung infection (CT) and alveolar macrophages to theR24 AA01943 Monkey Alcohol Tissue Research Resource (MATRR). This added capacity will be a resourcefor investigators to understand19the potentially complex relationships between alcohol consumption and COVID-related-outcomes and to enhance the nation's response to the current pandemic.