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Principal Investigator: YOSHIHIRO KAWAOKA
Organization: UNIVERSITY OF WISCONSIN-MADISON
Fiscal Year: 2021
Award: $194,375
Funding agency: National Institute of Allergy and Infectious Diseases
PROJECT SUMMARY
The pandemic SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) virus can cause severe and
even fatal infections in some patients, primarily those with comorbidities such as hypertension, diabetes mellitus,
obesity, and cardiovascular disease. In addition, immunocompromised patients are also at a high risk of severe
COVID-19, the disease caused by SARS-CoV-2. Animal models are vital for the testing of preventative and
therapeutic approaches to COVID-19, but models that recapitulate the major comorbidities associated with
COVID-19 are lacking. Recently, we established Syrian hamsters as a robust animal model for COVID-19
research. Building on our work with this model, we here plan to develop and evaluate diabetic (Aim 1), obese
(Aim 2), cardiomyopathic (Aim 3), and immunocompromised (Aim 4) Syrian hamsters for COVID-19 research.
For Aim 1 (‘To evaluate diabetic Syrian hamsters for COVID-19 research’), we have already demonstrated our
ability to generate diabetic Syrian hamsters by treating them with streptozotocin, a drug commonly used to
establish diabetic animal models. A high-fat diet will be used to generate obese hamsters for studies in Aim 2
(‘To establish obese Syrian hamsters for COVID-19 research’). Studies in Aim 3 (‘To evaluate cardiomyopathic
Syrian hamsters for COVID-19 research’) will be conducted with BIO14.6 Syrian hamsters, an established
cardiomyopathic disease model. An immunocompromised status will be induced by treating animals with
cyclophosphamide (a drug commonly used to induce immunosuppression) for studies in Aim 4 (‘To establish
immunocompromised Syrian hamsters for COVID-19 research’). Specific markers, such as blood glucose levels
(for diabetes), leptin levels (for obesity), troponin T levels (cardiovascular injury) and leukocytes counts (for
immunosuppression) will allow us to monitor the disease states. Animals will then be infected with SARS-CoV-
2, and virus titers in different organs will be measured at different timepoints post-infection. In addition, we will
measure the duration of virus shedding and the efficiency of virus transmission, both of which may be increased
in co-morbid compared with healthy SARS-CoV-2-infected animals. We will also assess the susceptibility for
reinfection with SARS-CoV-2 of both healthy and co-morbid Syrian hamsters. The comorbidities tested here
result in chronic inflammation and/or impaired immune responses. Therefore, the levels of several pro-
inflammatory cytokines and antibodies to SARS-CoV-2 in serum samples from these hamsters will be evaluated.
Collectively, we will establish and test several Syrian hamster comorbidity models for SARS-CoV-2 research.
Our data should provide a solid platform for the use of co-morbid Syrian hamster models in the testing of vaccines
and antiviral compounds for SARS-CoV-2.
Terms: <2019 novel corona virus><2019 novel coronavirus><2019-nCoV><ACE2><ARDS><Acute Respiratory Distress><Acute Respiratory Distress Syndrome><Address><Adult ARDS><Adult RDS><Adult Respiratory Distress Syndrome><After Care><After-Treatment><Aftercare><Age><Animal Feed><Animal Model><Animal Models and Related Studies><Animals><Anti-viral Drug Resistance><Anti-viral Drug Resistant><Antiviral Agents><Antiviral Drug Resistance><Antiviral Drug Resistant><Antiviral Drugs><Antivirals><Blood Glucose><Blood Serum><Blood Sugar><COVID crisis><COVID epidemic><COVID infected patient><COVID pandemic><COVID patient><COVID positive patient><COVID-19><COVID-19 antibody><COVID-19 crisis><COVID-19 epidemic><COVID-19 global health crisis><COVID-19 global pandemic><COVID-19 health crisis><COVID-19 infected patient><COVID-19 infection><COVID-19 pandemic><COVID-19 patient><COVID-19 positive patient><COVID-19 public health crisis><COVID-19 therapy><COVID-19 treatment><COVID-19 virus><COVID19><COVID19 crisis><COVID19 epidemic><COVID19 global health crisis><COVID19 global pandemic><COVID19 health crisis><COVID19 infection><COVID19 pandemic><COVID19 patient><COVID19 positive patient><COVID19 public health crisis><COVID19 therapy><COVID19 treatment><COVID19 virus><CTX><CV-19><CV19><CYCLO-cell><Cardiac Muscle Cells><Cardiac Myocytes><Cardiocyte><Cardiovascular Diseases><Carloxan><Cell Body><Cells><Cessation of life><Chemotactic Cytokines><Chronic><Ciclofosfamida><Ciclofosfamide><Cicloxal><Clafen><Claphene><CoV emergence><CoV-2><CoV2><Cricetinae><Cycloblastin><Cycloblastine><Cyclophospham><Cyclophosphamide><Cyclophosphamidum><Cyclophosphan><Cyclophosphane><Cyclophosphanum><Cyclostin><Cyclostine><Cytophosphan><Cytophosphane><Cytoxan><D-Glucose><Da Nang Lung><Data><Death><Dextrose><Diabetes Mellitus><Disease><Disease Outbreaks><Disease model><Disorder><Drugs><Endoxan><Endoxana><Enduxan><Evaluation><Fosfaseron><Genoxal><Genuxal><Glucose><Golden Hamsters><Golden Syrian Hamsters><Hamsters><Hamsters Mammals><Heart Muscle Cells><Heart myocyte><High Fat Diet><Homologous Chemotactic Cytokines><Human><Hypertension><Immune response><Immune system><Immunocompromised><Immunocompromised Host><Immunocompromised Patient><Immunological response><Immunosuppressed Host><Immunosuppression><Immunosuppression Effect><Immunosuppressive Effect><Impairment><Individual><Infection><Inflammation><Inflammatory><Intercrines><Lead><Ledoxina><Leptin><Leukocyte Count><Leukocyte Number><Lower Respiratory Tract Infection><Lower respiratory infection><MOF syndrome><Measures><Medication><Mesocricetus auratus><Meta-Analysis><Mitoxan><Modeling><Modern Man><Monitor><Multiple Organ Dysfunction Syndrome><Multiple Organ Failure><Names><Neosar><Ob Gene Product><Ob Protein><Obese Gene Product><Obese Protein><Obesity><Organ><Outbreaks><Outcome><Pathogenicity><Patients><Pb element><Pharmaceutic Preparations><Pharmaceutical Preparations><Predisposition><Procytox><Prognosis><Receptor Protein><Research><Respiratory Infections><Respiratory Tract Infections><Risk Factors><SARS Virus><SARS corona virus><SARS corona virus 2><SARS coronavirus><SARS-Associated Coronavirus><SARS-CoV><SARS-CoV-2><SARS-CoV-2 antibody><SARS-CoV-2 epidemic><SARS-CoV-2 global health crisis><SARS-CoV-2 global pandemic><SARS-CoV-2 infected patient><SARS-CoV-2 infection><SARS-CoV-2 pandemic><SARS-CoV-2 patient><SARS-CoV-2 positive patient><SARS-CoV-2 therapy><SARS-CoV-2 treatment><SARS-CoV2><SARS-CoV2 antibody><SARS-CoV2 epidemic><SARS-CoV2 infection><SARS-CoV2 pandemic><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><SIS cytokines><STZ><Sampling><Sendoxan><Serum><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 CoV 2><Severe Acute Respiratory Syndrome CoV 2 epidemic><Severe Acute Respiratory Syndrome CoV 2 pandemic><Severe Acute Respiratory Syndrome Virus><Severe Acute Respiratory Syndrome corona virus><Severe Acute Respiratory Syndrome coronavirus><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 epidemic><Severe acute respiratory syndrome coronavirus 2 infection><Severe acute respiratory syndrome coronavirus 2 pandemic><Severe acute respiratory syndrome related corona virus 2><Shock Lung><Solid><Stiff lung><Streptozocin><Streptozotocin><Susceptibility><Syklofosfamid><Syrian Hamsters><Test Result><Testing><Therapeutic><Troponin T><Up-Regulation><Upregulation><Vascular Hypertensive Disease><Vascular Hypertensive Disorder><Viral Diseases><Viral Drug Resistance><Viral Shedding><Virus><Virus Diseases><Virus Shedding><White Blood Cell Count><White Blood Cell Count procedure><Work><Wuhan coronavirus><Zanosar><Zytoxan><adiposity><ages><allergic/immunologic body system><allergic/immunologic organ system><angiotensin converting enzyme 2><angiotensin converting enzyme II><animal food><anti-viral agents><anti-viral drugs><anti-virals><antibody against COVID-19><antibody against SARS-CoV-2><antibody against SARS-CoV2><antibody against coronavirus disease 2019><antibody against severe acute respiratory syndrome coronavirus 2><antibody to COVID-19><antibody to SARS-CoV-2><antibody to SARS-CoV2><antibody to coronavirus disease 2019><antibody to severe acute respiratory syndrome coronavirus 2><cardiomyocyte><cardiovascular disorder><cardiovascular injury><chemoattractant cytokine><chemokine><chronic infection><co-morbid><co-morbidity><comorbidity><corona virus 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model><drug/agent><emergent CoV><emergent corona virus><emergent coronavirus><emerging CoV><emerging corona virus><emerging coronavirus><evaluate vaccines><experience><hCoV19><heavy metal Pb><heavy metal lead><high blood pressure><high risk><host response><hyperpiesia><hyperpiesis><hypertensive disease><immune suppression><immune system response><immunoresponse><immunosuppressed><immunosuppressed patient><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><life-threatening COVID><life-threatening COVID-19><life-threatening SARS-CoV-2><life-threatening coronavirus disease><life-threatening coronavirus disease 2019><life-threatening severe acute respiratory syndrome coronavirus 2><male><model of animal><model organism><multiorgan failure><multiple organ system failure><mutant><nCoV><nCoV2><new CoV><new corona virus><new 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transmission><virus-induced disease><wet lung>