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Principal Investigator: Kristina L Bailey
Organization: OMAHA VA MEDICAL CENTER
Fiscal Year: 2021
Funding agency: Veterans Affairs
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.
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