Rocky Mountain Veterinary Branch, Division of Intramural Research, National Institutes of Allergy and Infectious Diseases, National Institutes of Health, Rocky Mountain Laboratories, Hamilton, MT, USA.
Laboratory of Virology, Division of Intramural Research, National Institutes of Allergy and Infectious Diseases, National Institutes of Health, Rocky Mountain Laboratories, Hamilton, MT, USA.
Vet Pathol. 2022 Jul;59(4):673-680. doi: 10.1177/03009858211067468. Epub 2021 Dec 29.
Coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is an emergent, amphixenotic infection that resulted in a pandemic declaration in March 2020. A rapid search for appropriate animal models of this newly emergent viral respiratory disease focused initially on traditional nonhuman primate research species. Nonhuman primate models have previously been shown to be valuable in evaluation of emerging respiratory coronaviruses with pandemic potential (ie, SARS-CoV and Middle East respiratory syndrome coronavirus). In this article, we review the pulmonary histopathologic characteristics and immunohistochemical evaluation of experimental SARS-CoV-2 infection in the rhesus macaque, pigtail macaque, African green monkey, and squirrel monkey. Our results indicate that all evaluated nonhuman primate species developed variably severe histopathologic changes typical of coronavirus respiratory disease characterized by interstitial pneumonia with or without syncytial cell formation, alveolar fibrin, and pulmonary edema that progressed to type II pneumocyte hyperplasia. Lesion distribution was multifocal, frequently subpleural, and often more severe in lower lung lobes. However, squirrel monkeys showed the least severe and least consistent lesions of the evaluated nonhuman primates. Additionally, our results highlight the disparate physical relationship between viral antigen and foci of pulmonary lesions. While classic respiratory coronaviral lesions were observed in the lungs of all nonhuman primates evaluated, none of the primates exhibited severe lesions or evidence of diffuse alveolar damage and therefore are unlikely to represent the severe form of SARS-CoV-2 infection observed in fatal human cases.
新型冠状病毒病（COVID-19）由严重急性呼吸系统综合征冠状病毒 2 型（SARS-CoV-2）引起，是一种新发的、广泛宿主感染的疾病，于 2020 年 3 月宣布大流行。为寻找针对这种新发病毒性呼吸道疾病的合适动物模型，人们迅速将研究重点放在传统的非人类灵长类动物研究物种上。非人类灵长类动物模型此前已被证明可用于评估具有大流行潜力的新发呼吸道冠状病毒（例如 SARS-CoV 和中东呼吸综合征冠状病毒）。在本文中，我们回顾了恒河猴、食蟹猴、绿猴和松鼠猴中实验性 SARS-CoV-2 感染的肺组织病理学特征和免疫组织化学评估。我们的研究结果表明，所有评估的非人类灵长类动物均发生了不同程度的严重组织病理学变化，这些变化典型地表现为冠状病毒性呼吸道疾病，特征为间质肺炎伴或不伴合胞体细胞形成、肺泡纤维蛋白和肺水肿，进而发展为 II 型肺泡细胞增生。病变分布为多灶性，常位于胸膜下，且常以下肺叶更严重。然而，松鼠猴表现出评估的非人类灵长类动物中最不严重和最不一致的病变。此外，我们的研究结果强调了病毒抗原与肺部病变灶之间的不同物理关系。虽然在所有评估的非人类灵长类动物的肺部均观察到了典型的呼吸道冠状病毒病变，但没有一种灵长类动物表现出严重病变或弥漫性肺泡损伤的证据，因此不太可能代表在致命的人类病例中观察到的严重 SARS-CoV-2 感染形式。
