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Principal Investigator: Carl W White
Organization: UNIVERSITY OF COLORADO DENVER
Fiscal Year: 2021
Award: $182,367
Funding agency: National Institute of Environmental Health Sciences
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.
Terms: <2-Propenal><2019 novel corona virus><2019 novel coronavirus><2019-nCoV><2019-nCoV S protein><2019-nCoV spike glycoprotein><2019-nCoV spike protein><ACE2><ARDS><Acetaldehyde><Acraldehyde><Acrolein><Acrylaldehyde><Acrylic Aldehyde><Acute><Acute Lung Injury><Acute Pulmonary Injury><Acute Renal Failure with Renal Papillary Necrosis><Acute Respiratory Distress><Acute Respiratory Distress Syndrome><Address><Adult ARDS><Adult RDS><Adult Respiratory Distress Syndrome><Affect><Aldehydes><Alimentary Canal><Allyl Aldehyde><American><Angiotensins><Animal Model><Animal Models and Related Studies><Anti-Inflammatories><Anti-Inflammatory Agents><Anti-inflammatory><Antiinflammatories><Antiinflammatory Agents><Asthma><Autopsy><BSL-3 facility><BSL3 facility><Bacterial Pneumonia><Behavior><Behavioral><Binding><Blood Clotting><Blood Coagulation Disorders><Blood Vessels><Blood coagulation><Body Tissues><Bronchial Asthma><Buccal Cavity><Buccal Cavity Head and Neck><COPD><COVID crisis><COVID epidemic><COVID pandemic><COVID-19><COVID-19 S protein><COVID-19 crisis><COVID-19 epidemic><COVID-19 global health crisis><COVID-19 global pandemic><COVID-19 health crisis><COVID-19 infection><COVID-19 pandemic><COVID-19 predisposition><COVID-19 public health crisis><COVID-19 spike glycoprotein><COVID-19 spike protein><COVID-19 susceptibility><COVID-19 virus><COVID-19 vulnerability><COVID19><COVID19 S protein><COVID19 crisis><COVID19 epidemic><COVID19 global health crisis><COVID19 global pandemic><COVID19 health crisis><COVID19 infection><COVID19 pandemic><COVID19 public health crisis><COVID19 spike glycoprotein><COVID19 spike protein><COVID19 virus><CV-19><CV19><Camels><Cardiovascular Diseases><Cause of Death><Cavitas Oris><Cell surface><Characteristics><Chemicals><Chronic Obstruction Pulmonary Disease><Chronic Obstructive Airway Disease><Chronic Obstructive Lung Disease><Chronic Obstructive Pulmonary Disease><CoV-2><CoV2><Coagulation Disorder><Coagulopathy><Colorado><Common Rat Strains><Computer software><Coronaviridae><Coronavirus><Coronavirus disease 2019 predisposition><Coronavirus disease 2019 susceptibility><Coronavirus disease 2019 vulnerability><Cricetinae><Critical Illness><Critically Ill><Da Nang Lung><Devices><Digestive Tract><Disease><Disorder><Docking><Dromedaries><Electronic cigarette><Equilibrium><Ethanal><Ethylene Aldehyde><Event><Face><Ferrets><Flavorant><Flavoring><Flavoring Agents><Formaldehyde><Formic Aldehyde><GI Tract><Gastrointestinal Tract><Gastrointestinal tract structure><Genetic><Goals><Golden Hamsters><Golden Syrian Hamsters><Hamsters><Hamsters Mammals><Histopathology><Human><Infection><Institution><K-18><K-18 conjugate><K18><K18 combination><Laboratories><Lung><Lung Respiratory System><Lung damage><Lung diseases><MOF syndrome><Mediating><Medical><Mesocricetus auratus><Methyl Aldehyde><Mice><Mice Mammals><Modeling><Modern Man><Modification><Molecular Interaction><Monitor><Mouse Strains><Mouth><Multiple Organ Dysfunction Syndrome><Multiple Organ Failure><Murine><Mus><NIH><Nasal><Nasal Passages Nose><National Institutes of Health><Nicotine><Nose><Oral cavity><Outcome><Oxomethane><Particulate><Pathogenesis><Pathway interactions><Peptides><Pharmacology><Physiologic><Physiological><Pneumonia><Poison><Population><Predisposed to COVID-19><Predisposed to SARS-CoV-2><Predisposed to Severe acute respiratory syndrome coronavirus 2><Process><Propanediols><Propylene Glycols><Proteins><Pulmonary Body System><Pulmonary Diseases><Pulmonary Disorder><Pulmonary Organ System><Rat><Rats Mammals><Rattus><Receptor Protein><Renin-Angiotensin System><Research><Respiratory Disease><Respiratory System><Respiratory System Disease><Respiratory System Disorder><Respiratory System, Nose, Nasal Passages><Respiratory Tracts><Respiratory tract structure><Rhabdomyolysis><Robot><Rodent><Rodentia><Rodents Mammals><SARS><SARS Virus><SARS corona virus><SARS corona virus 2><SARS coronavirus><SARS coronavirus disease><SARS-Associated Coronavirus><SARS-CoV><SARS-CoV disease><SARS-CoV-2><SARS-CoV-2 S protein><SARS-CoV-2 epidemic><SARS-CoV-2 global health crisis><SARS-CoV-2 global pandemic><SARS-CoV-2 infection><SARS-CoV-2 pandemic><SARS-CoV-2 predisposition><SARS-CoV-2 spike glycoprotein><SARS-CoV-2 spike protein><SARS-CoV-2 susceptibility><SARS-CoV-2 vulnerability><SARS-CoV2><SARS-CoV2 S protein><SARS-CoV2 epidemic><SARS-CoV2 infection><SARS-CoV2 pandemic><SARS-CoV2 spike glycoprotein><SARS-CoV2 spike protein><SARS-Related Coronavirus><SARS-associated corona virus 2><SARS-associated coronavirus 2><SARS-coronavirus-2><SARS-coronavirus-2 epidemic><SARS-coronavirus-2 pandemic><SARS-related corona virus 2><SARS-related coronavirus 2><SARSCoV2><Septic Shock><Severe Acute Respiratory Distress Syndrome CoV 2><Severe Acute Respiratory Distress Syndrome Corona Virus 2><Severe Acute Respiratory Distress Syndrome Coronavirus 2><Severe Acute Respiratory Syndrome><Severe Acute Respiratory Syndrome CoV 2><Severe Acute Respiratory Syndrome CoV 2 epidemic><Severe Acute Respiratory Syndrome CoV 2 pandemic><Severe Acute Respiratory Syndrome CoV disease><Severe Acute Respiratory Syndrome Virus><Severe Acute Respiratory Syndrome corona virus><Severe Acute Respiratory Syndrome coronavirus><Severe Acute Respiratory Syndrome coronavirus disease><Severe Acute Respiratory Syndrome-associated coronavirus 2><Severe Acute Respiratory Syndrome-related coronavirus 2><Severe acute respiratory syndrome associated corona virus 2><Severe acute respiratory syndrome corona virus 2><Severe acute respiratory syndrome coronavirus 2><Severe acute respiratory syndrome coronavirus 2 S protein><Severe acute respiratory syndrome coronavirus 2 epidemic><Severe acute respiratory syndrome coronavirus 2 infection><Severe acute respiratory syndrome coronavirus 2 pandemic><Severe acute respiratory syndrome coronavirus 2 predisposition><Severe acute respiratory syndrome coronavirus 2 spike glycoprotein><Severe acute respiratory syndrome coronavirus 2 spike protein><Severe acute respiratory syndrome coronavirus 2 susceptibility><Severe acute respiratory syndrome coronavirus 2 vulnerability><Severe acute respiratory syndrome related corona virus 2><Severities><Severity of illness><Shock Lung><Site><Smoker><Smoking><Software><Stiff lung><Structure><Surface><Syrian Hamsters><Thrombosis><Tissues><Touch><Touch sensation><Toxic Chemical><Toxic Substance><Toxicology><Transgenic Mice><United States National Institutes of Health><Universities><Vasoactive Agonists><Vasoconstrictor Agents><Vasoconstrictor Drugs><Vasoconstrictors><Vasopressor Agents><Viral Burden><Viral Load><Viral Load result><Viral Pneumonia><Virus><Wuhan coronavirus><Yin-Yang><acryaldehyde><acute kidney injury><airway epithelium><alimentary tract><angiotensin converting enzyme 2><angiotensin converting enzyme II><antiinflammatory><bacteria pneumonia><balance><balance function><biosafety level 3 facility><bleeding disorder><cardiovascular disorder><cardiovascular endothelium><cigarette smoking><cigarette use><clotting disorder><combustible cigarette><computerized><conventional cigarette><corona virus><corona virus disease 2019><corona virus disease 2019 epidemic><corona virus disease 2019 pandemic><coronavirus disease 2019><coronavirus disease 2019 S protein><coronavirus disease 2019 crisis><coronavirus disease 2019 epidemic><coronavirus disease 2019 global health crisis><coronavirus disease 2019 global pandemic><coronavirus disease 2019 health crisis><coronavirus disease 2019 infection><coronavirus disease 2019 pandemic><coronavirus disease 2019 public health crisis><coronavirus disease 2019 spike glycoprotein><coronavirus disease 2019 spike protein><coronavirus disease 2019 virus><coronavirus disease crisis><coronavirus disease epidemic><coronavirus disease pandemic><cytokine release syndrome><cytokine storm><digestive canal><disease of the lung><disease severity><disorder of the lung><e-cig><e-cig use><e-cigarette><e-cigarette use><ecig><ecig use><ecigarette><ecigarette use><effective therapy><effective treatment><electronic cigarette use><emerging pathogen><ex-smoker><faces><facial><former smoker><full professor><hCoV19><infected with COVID-19><infected with COVID19><infected with SARS-CoV-2><infected with SARS-CoV2><infected with coronavirus disease 2019><infected with severe acute respiratory syndrome coronavirus 2><infection rate><interest><intestinal epithelium><lung disorder><lung injury><medically disadvantaged><medically disadvantaged population><medically under served group><medically under served population><medically underserved group><medically underserved population><member><model of animal><model organism><mortality><multiorgan failure><multiple organ system failure><nCoV2><necropsy><new pathogen><non-human primate><nonhuman primate><novel pathogen><pathway><pollutant><postmortem><predisposed to Coronavirus disease 2019><programs><pulmonary><rate of infection><receptor><senior faculty><severe acute respiratory syndrome coronavirus 2 global health crisis><severe acute respiratory syndrome coronavirus 2 global pandemic><severe acute respiratory syndrome-CoV><social><susceptible to COVID-19><susceptible to Coronavirus disease 2019><susceptible to SARS-CoV-2><susceptible to Severe acute respiratory syndrome coronavirus 2><tactile sensation><thrombotic><thrombotic disease><thrombotic disorder><toxic compound><traditional cigarette><vaping><vaping nicotine><vascular><vasopressor><vegetable glycerin><virology><wet lung>