Lung Innate COVID-19 Defense Specific to Veterans Risk Characteristics

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.