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Volume 40 Issue 3
June 2025

    . doi: 10.1016/j.virs.2025.05.001
    Citation: Hao-Feng Lin, Ren-Di Jiang, Rui-Xin Qin, Bing Yao, Wen-Tao Zeng, Yun Gao, Ai-Min Shi, Jian-Min Li, Mei-Qin Liu. Characterization of a SARS-CoV-2 infection model in golden hamsters with diabetes mellitus .VIROLOGICA SINICA, 2025, 40(3) : 349-360.  http://dx.doi.org/10.1016/j.virs.2025.05.001
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    SARS-CoV-2糖尿病金黄地鼠模型感染特征

    • a. 广州医科大学附属第一医院, 呼吸疾病全国重点实验室;

    • b. 南京医科大学生殖医学国家重点实验室, 江苏省医药动物实验基地;

    • c. 粤港澳大湾区精准医学研究院;

    • d. 南京医科大学附属金陵医院生殖医学中心

    • 新型冠状病毒（SARS-CoV-2）在全球持续传播的过程中不断发生适应性进化，对公共卫生构成持久威胁，尤其对合并慢性基础疾病的高危人群影响更为显著。糖尿病是导致2019冠状病毒病（COVID-19）重症的高危因素之一，因此建立具有糖尿病病理特征的COVID-19动物模型具有重要研究价值。本研究构建的瘦素受体基因敲除地鼠（db/db）具有糖尿病表型，与野生型地鼠相比，糖尿病地鼠对SARS-CoV-2及其变异株更易感，并且可以引发肺部更强的免疫细胞因子反应。组织病理学分析显示SARS-CoV-2及其变异株会导致糖尿病地鼠更严重的肺组织损伤，并可能诱发糖尿病肾病和心脏病变等严重并发症。研究结果表明，尽管SARS-CoV-2变异株的呼吸道致病性有所减弱，但仍能对糖尿病地鼠的肾脏、心脏等器官造成损害，提示变异株对糖尿病患者的健康风险不容忽视。该地鼠模型有助于深入理解糖尿病患者发生COVID-19重症的致病机制，并为针对这一高危人群开发防治SARS-CoV-2变异株的有效疗法提供重要实验平台。

    Characterization of a SARS-CoV-2 infection model in golden hamsters with diabetes mellitus

    • a. The First Affiliated Hospital of Guangzhou Medical University, Guangzhou Laboratory Clinical Base, State Key Laboratory of Respiratory Disease, Guangzhou Medical University, Guangzhou, 510120, China;

    • b. State Key Laboratory of Reproductive Medicine and Offspring Health, Jiangsu Laboratory Animal Center, Jiangsu Animal Experimental Center of Medicine and Pharmacy, Department of Cell Biology, Animal Core facility, Key Laboratory of Model Animal, Collaborative Innovation Center for Cardiovascular Disease Translational Medicine, National Vaccine Innovation Platform, Nanjing Medical University, Nanjing, 211166, China;

    • c. State Key Laboratory of Genetic Engineering, Greater Bay Area Institute of Precision Medicine (Guangzhou), School of Life Sciences, Zhongshan Hospital, Fudan University, Shanghai, 200433, China;

    • d. Jinling Hospital Department Reproductive Medical Center, Nanjing Medical University, Nanjing, 211166, China

    • Being widespread across the globe, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) keeps evolving and generating new variants and continuously poses threat to public health, especially to the population with chronic comorbidities. Diabetes mellitus is one of high-risk factors for severe outcome of coronavirus disease 2019 (COVID-19). Establishment of animal models that parallel the clinical and pathological features of COVID-19 complicated with diabetes is thus highly essential. Here, in this study, we constructed leptin receptor gene knockout hamsters with the phenotype of diabetes mellitus (db/db), and revealed that the diabetic hamsters were more susceptible to SARS-CoV-2 and its variants than wild-type hamsters. SARS-CoV-2 and its variants induced a stronger immune cytokine response in the lungs of diabetic hamsters than in wild-type hamsters. Comparative histopathology analyses also showed that infection of SARS-CoV-2 and the variants caused more severe lung tissue injury in diabetic hamsters, and may induce serious complications such as diabetic kidney disease and cardiac lesions. Our findings demonstrated that despite the decreased respiratory pathogenicity, the SARS-CoV-2 variants were still capable of impairing other organs such as kidney and heart in diabetic hamsters, suggesting that the risk of evolving SARS-CoV-2 variants to diabetic patients should never be neglected. This hamster model may help better understand the pathogenesis mechanism of severe COVID-19 in patients with diabetes. It will also aid in development and testing of effective therapeutics and prophylactic treatments against SARS-CoV-2 variants among these high-risk populations.
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      Characterization of a SARS-CoV-2 infection model in golden hamsters with diabetes mellitus

        Corresponding author: Yun Gao, yun@njmu.edu.cn
        Corresponding author: Ai-Min Shi, sam@njmu.edu.cn
        Corresponding author: Jian-Min Li, jianminlilab@njmu.edu.cn
        Corresponding author: Mei-Qin Liu, 2023390024@gzhmu.edu.cn
      • a. The First Affiliated Hospital of Guangzhou Medical University, Guangzhou Laboratory Clinical Base, State Key Laboratory of Respiratory Disease, Guangzhou Medical University, Guangzhou, 510120, China;
      • b. State Key Laboratory of Reproductive Medicine and Offspring Health, Jiangsu Laboratory Animal Center, Jiangsu Animal Experimental Center of Medicine and Pharmacy, Department of Cell Biology, Animal Core facility, Key Laboratory of Model Animal, Collaborative Innovation Center for Cardiovascular Disease Translational Medicine, National Vaccine Innovation Platform, Nanjing Medical University, Nanjing, 211166, China;
      • c. State Key Laboratory of Genetic Engineering, Greater Bay Area Institute of Precision Medicine (Guangzhou), School of Life Sciences, Zhongshan Hospital, Fudan University, Shanghai, 200433, China;
      • d. Jinling Hospital Department Reproductive Medical Center, Nanjing Medical University, Nanjing, 211166, China
      • Received Date: 23 November 2024
      • Accepted Date: 12 May 2025

      Abstract: Being widespread across the globe, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) keeps evolving and generating new variants and continuously poses threat to public health, especially to the population with chronic comorbidities. Diabetes mellitus is one of high-risk factors for severe outcome of coronavirus disease 2019 (COVID-19). Establishment of animal models that parallel the clinical and pathological features of COVID-19 complicated with diabetes is thus highly essential. Here, in this study, we constructed leptin receptor gene knockout hamsters with the phenotype of diabetes mellitus (db/db), and revealed that the diabetic hamsters were more susceptible to SARS-CoV-2 and its variants than wild-type hamsters. SARS-CoV-2 and its variants induced a stronger immune cytokine response in the lungs of diabetic hamsters than in wild-type hamsters. Comparative histopathology analyses also showed that infection of SARS-CoV-2 and the variants caused more severe lung tissue injury in diabetic hamsters, and may induce serious complications such as diabetic kidney disease and cardiac lesions. Our findings demonstrated that despite the decreased respiratory pathogenicity, the SARS-CoV-2 variants were still capable of impairing other organs such as kidney and heart in diabetic hamsters, suggesting that the risk of evolving SARS-CoV-2 variants to diabetic patients should never be neglected. This hamster model may help better understand the pathogenesis mechanism of severe COVID-19 in patients with diabetes. It will also aid in development and testing of effective therapeutics and prophylactic treatments against SARS-CoV-2 variants among these high-risk populations.

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