Virology Division, United States Army Medical Research Institute of Infectious Diseases (USAMRIID), Fort Detrick, Frederick, MD 21702, USA.
Diagnostic Systems Division, USAMRIID, Fort Detrick, Frederick, MD 21702, USA.
Viruses. 2022 May 10;14(5):1013. doi: 10.3390/v14051013.
The emergence of SARS-CoV-2 and the subsequent pandemic has highlighted the need for animal models that faithfully replicate the salient features of COVID-19 disease in humans. These models are necessary for the rapid selection, testing, and evaluation of potential medical countermeasures. Here, we performed a direct comparison of two distinct routes of SARS-CoV-2 exposure-combined intratracheal/intranasal and small particle aerosol-in two nonhuman primate species, rhesus and cynomolgus macaques. While all four experimental groups displayed very few outward clinical signs, evidence of mild to moderate respiratory disease was present on radiographs and at necropsy. Cynomolgus macaques exposed via the aerosol route also developed the most consistent fever responses and had the most severe respiratory disease and pathology. This study demonstrates that while all four models produced suitable representations of mild COVID-like illness, aerosol exposure of cynomolgus macaques to SARS-CoV-2 produced the most severe disease, which may provide additional clinical endpoints for evaluating therapeutics and vaccines.
SARS-CoV-2 的出现及其引发的大流行凸显了对动物模型的需求，这些模型能够忠实地复制人类 COVID-19 疾病的显著特征。这些模型对于快速选择、测试和评估潜在的医疗对策是必要的。在这里，我们在两种非人类灵长类动物——恒河猴和食蟹猴中，直接比较了两种不同的 SARS-CoV-2 暴露途径——联合气管内/鼻腔内和小颗粒气溶胶。虽然所有四个实验组的外在临床症状都很少，但 X 光和尸检显示出轻度至中度呼吸道疾病的证据。通过气溶胶途径暴露的食蟹猴也出现了最一致的发热反应，并且呼吸道疾病和病理学最严重。这项研究表明，虽然所有四种模型都能很好地模拟轻度 COVID 样疾病，但 SARS-CoV-2 气溶胶暴露于食蟹猴会导致最严重的疾病，这可能为评估治疗药物和疫苗提供更多的临床终点。
