Lin Hao-Feng, Jiang Ren-Di, Qin Rui-Xin, Yao Bing, Zeng Wen-Tao, Gao Yun, Shi Ai-Min, Li Jian-Min, Liu Mei-Qin
The First Affiliated Hospital of Guangzhou Medical University, Guangzhou Laboratory Clinical Base, State Key Laboratory of Respiratory Disease, Guangzhou Medical University, Guangzhou, 510120, China.
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.
Virol Sin. 2025 Jun;40(3):349-360. doi: 10.1016/j.virs.2025.05.001. Epub 2025 May 17.
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.
严重急性呼吸综合征冠状病毒2（SARS-CoV-2）在全球广泛传播，不断进化并产生新的变体，持续对公众健康构成威胁，尤其是对患有慢性合并症的人群。糖尿病是2019冠状病毒病（COVID-19）严重后果的高危因素之一。因此，建立与COVID-19合并糖尿病临床和病理特征相似的动物模型至关重要。在此项研究中，我们构建了具有糖尿病表型的瘦素受体基因敲除仓鼠（db/db），并发现糖尿病仓鼠比野生型仓鼠更容易感染SARS-CoV-2及其变体。SARS-CoV-2及其变体在糖尿病仓鼠肺部诱导的免疫细胞因子反应比野生型仓鼠更强。比较组织病理学分析还表明，SARS-CoV-2及其变体感染在糖尿病仓鼠中导致更严重的肺组织损伤，并可能引发糖尿病肾病和心脏病变等严重并发症。我们的研究结果表明，尽管SARS-CoV-2变体的呼吸道致病性有所降低，但仍能够损害糖尿病仓鼠的肾脏和心脏等其他器官，这表明SARS-CoV-2变体对糖尿病患者的风险绝不能被忽视。这种仓鼠模型可能有助于更好地理解糖尿病患者中重症COVID-19的发病机制。它还将有助于在这些高危人群中开发和测试针对SARS-CoV-2变体的有效治疗方法和预防措施。
