Non-human primate models will expedite therapeutics and vaccines for coronavirus disease 2019 (COVID-19) to clinical trials. Here, we compare acute severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in young and old rhesus macaques, baboons and old marmosets. Macaques had clinical signs of viral infection, mild to moderate pneumonitis and extra-pulmonary pathologies, and both age groups recovered in two weeks. Baboons had prolonged viral RNA shedding and substantially more lung inflammation compared with macaques. Inflammation in bronchoalveolar lavage was increased in old versus young baboons. Using techniques including computed tomography imaging, immunophenotyping, and alveolar/peripheral cytokine response and immunohistochemical analyses, we delineated cellular immune responses to SARS-CoV-2 infection in macaque and baboon lungs, including innate and adaptive immune cells and a prominent type-I interferon response. Macaques developed T-cell memory phenotypes/responses and bystander cytokine production. Old macaques had lower titres of SARS-CoV-2-specific IgG antibody levels compared with young macaques. Acute respiratory distress in macaques and baboons recapitulates the progression of COVID-19 in humans, making them suitable as models to test vaccines and therapies.

非人类灵长类动物模型将加快 2019 年冠状病毒病 (COVID-19) 的治疗方法和疫苗进入临床试验。在这里，我们比较了年轻和年老恒河猴、狒狒和年老狨猴中的急性严重急性呼吸综合征冠状病毒 2 (SARS-CoV-2) 感染情况。猕猴有病毒感染、轻度至中度肺炎和肺外病变的临床症状，两个年龄组均在两周内康复。与猕猴相比，狒狒的病毒 RNA 脱落时间更长，肺部炎症也明显更多。与年轻狒狒相比，年老狒狒支气管肺泡灌洗中的炎症增加。利用计算机断层扫描成像、免疫表型分析、肺泡/外周细胞因子反应和免疫组织化学分析等技术，我们描绘了猕猴和狒狒肺部对 SARS-CoV-2 感染的细胞免疫反应，包括先天性和适应性免疫细胞以及一种重要的 I 型干扰素回复。猕猴形成了 T 细胞记忆表型/反应和旁观者细胞因子的产生。与年轻猕猴相比，年老猕猴的 SARS-CoV-2 特异性 IgG 抗体滴度较低。猕猴和狒狒的急性呼吸窘迫再现了人类中 COVID-19 的进展情况，使它们适合作为测试疫苗和疗法的模型。