Heegaard Peter M H, Sturek Michael, Alloosh Mouhamad, Belsham Graham J
Department of Health Technology, Technical University of Denmark (DTU), Lyngby, Denmark.
Department of Anatomy, Cell Biology, and Physiology, Indiana University School of Medicine, Indianapolis, IN, United States.
Front Microbiol. 2020 Sep 25;11:573756. doi: 10.3389/fmicb.2020.573756. eCollection 2020.
The ongoing COVID-19 pandemic caused by infection with SARS-CoV-2 has created an urgent need for animal models to enable study of basic infection and disease mechanisms and for development of vaccines, therapeutics, and diagnostics. Most research on animal models for COVID-19 has been directed toward rodents, transgenic rodents, and non-human primates. The primary focus has been on the angiotensin-converting enzyme 2 (ACE2), which is a host cell receptor for SARS-CoV-2. Among investigated species, irrespective of ACE2 spike protein binding, only mild (or no) disease has occurred following infection with SARS-CoV-2, suggesting that ACE2 may be necessary for infection but is not sufficient to determine the outcome of infection. The common trait of all species investigated as COVID models is their healthy status prior to virus challenge. In contrast, the vast majority of severe COVID-19 cases occur in people with chronic comorbidities such as diabetes, obesity, and/or cardiovascular disease. Healthy pigs express ACE2 protein that binds the viral spike protein but they are not susceptible to infection with SARS-CoV-2. However, certain pig breeds, such as the Ossabaw pig, can reproducibly be made obese and show most aspects of the metabolic syndrome, thus resembling the more than 80% of the critically ill COVID-19 patients admitted to hospitals. We urge considering infection with porcine respiratory coronavirus of metabolic syndrome pigs, such as the obese Ossabaw pig, as a highly relevant animal model of severe COVID-19.
由严重急性呼吸综合征冠状病毒2（SARS-CoV-2）感染引起的持续新冠疫情，迫切需要动物模型来研究基本感染和疾病机制，以及开发疫苗、治疗方法和诊断手段。关于新冠病毒动物模型的大多数研究都针对啮齿动物、转基因啮齿动物和非人类灵长类动物。主要关注点是血管紧张素转换酶2（ACE2），它是SARS-CoV-2的宿主细胞受体。在被研究的物种中，无论ACE2刺突蛋白结合情况如何，感染SARS-CoV-2后仅出现轻度（或无）疾病，这表明ACE2可能是感染所必需的，但不足以决定感染的结果。所有作为新冠模型被研究的物种的共同特征是在病毒攻击前它们的健康状态。相比之下，绝大多数严重新冠病例发生在患有慢性合并症的人群中，如糖尿病、肥胖症和/或心血管疾病。健康猪表达与病毒刺突蛋白结合的ACE2蛋白，但它们不易感染SARS-CoV-2。然而，某些猪品种，如奥萨巴猪，可重复性地变得肥胖并表现出代谢综合征的大多数方面，因此类似于80%以上入住医院的重症新冠患者。我们敦促考虑将代谢综合征猪，如肥胖的奥萨巴猪，感染猪呼吸道冠状病毒，作为严重新冠的高度相关动物模型。
