Effect of vaping on COVID-19 infection

PROJECT SUMMARY In the COVID-19 pandemic, >1.5 million Americans have become ill, and over 100,000 have died. So far, medically underserved populations are more than twice as likely to die or develop critical illness relative to their proportion in the population. Current and former smokers are also more likely to develop critical COVID-19 and/or die. The basis for this could be social, behavioral and/or physiological. Recent findings show that smoking and nicotine may change the 'docking site' (ACE2) where the virus enters the airway epithelium. This study will explore the effect of vaping and nicotine in hamsters that are susceptible to COVID-19 to see if this changes their lung ACE2 expression and/or worsens their disease due to the SARS-CoV-2 virus. Vaping is a delivery device for the addicting, toxic and vasoactive compound nicotine. E-cigarette use, or dual use of traditional and e-cigarettes, has not been examined in the context of SARS-CoV-2 infection. Specifically, the effects of vaping and nicotine on COVID-19 lung disease severity, viral load, and ACE2/ACE expression at the message, protein and activity levels will be investigated. Thus, this model will be used to clarify the importance of vaping-induced lung injury on ACE2 expression and subsequent SARS2 infection and pathogenesis. To address these questions, we hypothesized that subacute and/or acute nicotine vaping could alter the ACE2/ACE activities and, potentially, lung histopathology in the hamster. Further, we postulated that acute/subacute vaping could increase SARS-CoV-2 infection and/or lung disease severity in the hamster. If true, pharmacologic modification of ACE2/ACE ratio in the vaping and/or nonvaping hamster could diminish SARS-CoV-2 infection severity. Two aims will be undertaken: 1) Define the effects of vaping nicotine on ACE2/ACE and lung histopathology in Syrian hamster, and 2)Define the effect of vaping on SARS-CoV-2 viral load, clearance, and COVID-19 lung disease in model(s) developed in Aim 1 APPROACH: We will use a newly acquired e-cigarette 'vaping robot' that is fully computerized and programmable using flexiWare software (inExpose, SCIREQ, Montreal) for nose-only delivery to rodents, and a recently described hamster model for SARS-CoV-2-mediated lung injury. The vaping exposures will be conducted at University of Colorado Anschutz Medical Campus (Denver), and, following brief transport, the COVID-19 model will be done at Colorado State University's (CSU) BSL3 facility (Ft. Collins, CO). There we will monitor hamsters for up to 7 days, with studies of airway/lung histopathology and ACE2/ACE expression after necropsy. The project involves two laboratories with long-standing research interests: acute lung injury and toxicology, and virology and emerging pathogens, respectively. We will better understand mechanism(s) for worsening COVID-19 in smokers, and potentially new pathways to their more effective treatment.