权益分类	功能权益	普通用户	{{item.name}}会员
{{category.name}}	{{benefitItem.name}}

COVID-19 comorbidity studies in Syrian hamster models

叙利亚仓鼠模型中的 COVID-19 合并症研究

基本信息

批准号：
10450889
负责人：
YOSHIHIRO KAWAOKA
金额：
$ 23.33万
依托单位：
UNIVERSITY OF WISCONSIN-MADISON
依托单位国家：
美国
项目类别：
财政年份：
2021
资助国家：
美国
起止时间：
2021-07-15 至 2023-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10450889
关键词：
2019-nCoV ACE2 Acute Respiratory Distress Syndrome Address Aftercare Age Animal Feed Animal Model Animals Antiviral Agents Blood Glucose COVID-19 COVID-19 pandemic COVID-19 patient COVID-19 treatment Cardiac Myocytes Cardiovascular Diseases Cells Cessation of life Chronic Cyclophosphamide Data Diabetes Mellitus Disease Disease Outbreaks Disease model Evaluation Glucose Hamsters High Fat Diet Human Hypertension Immune response Immune system Immunocompromised Host Immunosuppression Impairment Individual Infection Inflammation Inflammatory Lead Leptin Lower Respiratory Tract Infection Measures Mesocricetus auratus Meta-Analysis Modeling Monitor Multiple Organ Failure Names Obesity Organ Outcome Pathogenicity Patients Persons Pharmaceutical Preparations Predisposition Prognosis Research Respiratory Tract Infections Risk Factors SARS coronavirus SARS-CoV-2 antibody SARS-CoV-2 infection Sampling Serum Solid Streptozocin Test Result Testing Therapeutic Troponin T Up-Regulation Viral Drug Resistance Virus Virus Diseases Virus Shedding White Blood Cell Count procedure Work cardiovascular injury chemokine chronic infection comorbidity cytokine diabetic experience high risk immunosuppressed male mutant novel novel coronavirus novel virus pandemic disease receptor severe COVID-19 sex vaccine evaluation viral transmission

项目摘要

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.

项目总结