Tulane National Primate Research Center, Covington, Louisiana; Department of Pathology and Laboratory Animal Medicine, Tulane University School of Medicine, New Orleans, Louisiana.
Tulane National Primate Research Center, Covington, Louisiana; Department of Microbiology and Immunology, Tulane University School of Medicine, New Orleans, Louisiana.
Am J Pathol. 2021 Feb;191(2):274-282. doi: 10.1016/j.ajpath.2020.10.016. Epub 2020 Nov 7.
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) induces a wide range of disease severity, ranging from asymptomatic infection to a life-threating illness, particularly in the elderly population and individuals with comorbid conditions. Among individuals with serious coronavirus 2019 (COVID-19) disease, acute respiratory distress syndrome (ARDS) is a common and often fatal presentation. Animal models of SARS-CoV-2 infection that manifest severe disease are needed to investigate the pathogenesis of COVID-19-induced ARDS and evaluate therapeutic strategies. We report two cases of ARDS in two aged African green monkeys (AGMs) infected with SARS-CoV-2 that had pathological lesions and disease similar to severe COVID-19 in humans. We also report a comparatively mild COVID-19 phenotype characterized by minor clinical, radiographic, and histopathologic changes in the two surviving, aged AGMs and four rhesus macaques (RMs) infected with SARS-CoV-2. Notable increases in circulating cytokines were observed in three of four infected, aged AGMs but not in infected RMs. All the AGMs had increased levels of plasma IL-6 compared with baseline, a predictive marker and presumptive therapeutic target in humans infected with SARS-CoV-2. Together, our results indicate that both RMs and AGMs are capable of modeling SARS-CoV-2 infection and suggest that aged AGMs may be useful for modeling severe disease manifestations, including ARDS.
严重急性呼吸综合征冠状病毒 2(SARS-CoV-2)可引起广泛的疾病严重程度,从无症状感染到危及生命的疾病,特别是在老年人群体和合并症患者中。在患有严重的 2019 年冠状病毒病(COVID-19)的个体中,急性呼吸窘迫综合征(ARDS)是常见且常常致命的表现。需要具有严重 SARS-CoV-2 感染表现的动物模型来研究 COVID-19 诱导的 ARDS 的发病机制并评估治疗策略。我们报告了两例感染 SARS-CoV-2 的老年绿猴(AGM)发生 ARDS 的病例,这两例病例的病理损伤和疾病与人类严重 COVID-19 相似。我们还报告了两例存活的老年 AGM 和四例感染 SARS-CoV-2 的恒河猴(RM)中表现出的相对较轻的 COVID-19 表型,其特征为临床、影像学和组织病理学变化较小。在感染的四只老年 AGM 中有三只观察到循环细胞因子显著增加,但在感染的 RM 中没有观察到。与基线相比,所有 AGM 的血浆 IL-6 水平均升高,这是人类感染 SARS-CoV-2 的预测标志物和推定治疗靶标。总之,我们的结果表明,RM 和 AGM 均能够模拟 SARS-CoV-2 感染,并且老年 AGM 可能有助于模拟包括 ARDS 在内的严重疾病表现。