Experimental Medicine Department, King Abdullah International Medical Research Center/King Saud bin Abdulaziz University for Health Sciences, King Abdulaziz Medical City, Ministry of National Guard Health Affairs, Riyadh, Saudi Arabia.
Crit Care. 2020 Oct 6;24(1):594. doi: 10.1186/s13054-020-03304-8.
Animal models of COVID-19 have been rapidly reported after the start of the pandemic. We aimed to assess whether the newly created models reproduce the full spectrum of human COVID-19.
We searched the MEDLINE, as well as BioRxiv and MedRxiv preprint servers for original research published in English from January 1 to May 20, 2020. We used the search terms (COVID-19) OR (SARS-CoV-2) AND (animal models), (hamsters), (nonhuman primates), (macaques), (rodent), (mice), (rats), (ferrets), (rabbits), (cats), and (dogs). Inclusion criteria were the establishment of animal models of COVID-19 as an endpoint. Other inclusion criteria were assessment of prophylaxis, therapies, or vaccines, using animal models of COVID-19.
Thirteen peer-reviewed studies and 14 preprints met the inclusion criteria. The animals used were nonhuman primates (n = 13), mice (n = 7), ferrets (n = 4), hamsters (n = 4), and cats (n = 1). All animals supported high viral replication in the upper and lower respiratory tract associated with mild clinical manifestations, lung pathology, and full recovery. Older animals displayed relatively more severe illness than the younger ones. No animal models developed hypoxemic respiratory failure, multiple organ dysfunction, culminating in death. All species elicited a specific IgG antibodies response to the spike proteins, which were protective against a second exposure. Transient systemic inflammation was observed occasionally in nonhuman primates, hamsters, and mice. Notably, none of the animals unveiled a cytokine storm or coagulopathy.
Most of the animal models of COVID-19 recapitulated mild pattern of human COVID-19 with full recovery phenotype. No severe illness associated with mortality was observed, suggesting a wide gap between COVID-19 in humans and animal models.
大流行开始后，迅速报道了 COVID-19 的动物模型。我们旨在评估新创建的模型是否再现了人类 COVID-19 的全部特征。
我们在 MEDLINE 上，以及 BioRxiv 和 MedRxiv 预印本服务器上，对 2020 年 1 月 1 日至 5 月 20 日期间以英文发表的原始研究进行了检索。我们使用了以下检索词：(COVID-19)或(SARS-CoV-2)和(动物模型)、(仓鼠)、(非人类灵长类动物)、(猕猴)、(啮齿动物)、(老鼠)、(大鼠)、(雪貂)、(兔子)、(猫)和(狗)。纳入标准为将 COVID-19 动物模型作为终点建立。其他纳入标准为使用 COVID-19 动物模型评估预防、治疗或疫苗。
符合纳入标准的有 13 项同行评议研究和 14 项预印本。使用的动物是非人类灵长类动物(n=13)、老鼠(n=7)、雪貂(n=4)、仓鼠(n=4)和猫(n=1)。所有动物在上呼吸道和下呼吸道中均支持高病毒复制，与轻度临床症状、肺部病理学和完全康复相关。年龄较大的动物比年龄较小的动物患病相对严重。没有动物模型发展为低氧性呼吸衰竭、多器官功能障碍，最终导致死亡。所有物种对刺突蛋白均产生特异性 IgG 抗体反应，对第二次暴露具有保护作用。偶尔在非人类灵长类动物、仓鼠和小鼠中观察到短暂的全身炎症。值得注意的是，没有一种动物模型出现细胞因子风暴或凝血功能障碍。
大多数 COVID-19 动物模型再现了人类 COVID-19 的轻度模式，具有完全恢复表型。未观察到与死亡率相关的严重疾病，这表明 COVID-19 患者和动物模型之间存在很大差距。
