Key Laboratory of Jilin Province for Zoonosis Prevention and Control, Changchun Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Changchun, China.
Jiangsu Co-innovation Center for Prevention and Control of Important Animal Infectious Disease and Zoonoses, Yangzhou, China.
Front Immunol. 2022 Jul 12;13:954121. doi: 10.3389/fimmu.2022.954121. eCollection 2022.
Although tremendous effort has been exerted to elucidate the pathogenesis of severe COVID-19 cases, the detailed mechanism of moderate cases, which accounts for 90% of all patients, remains unclear yet, partly limited by lacking the biopsy tissues. Here, we established the COVID-19 infection model in cynomolgus macaques (CMs), monitored the clinical and pathological features, and analyzed underlying pathogenic mechanisms at early infection stage by performing proteomic and metabolomic profiling of lung tissues and sera samples from COVID-19 CMs models. Our data demonstrated that innate immune response, neutrophile and platelet activation were mainly dysregulated in COVID-19 CMs. The symptom of neutrophilia, lymphopenia and massive "cytokines storm", main features of severe COVID-19 patients, were greatly weakened in most of the challenged CMs, which are more semblable as moderate patients. Thus, COVID-19 model in CMs is rational to understand the pathogenesis of moderate COVID-19 and may be a candidate model to assess the safety and efficacy of therapeutics and vaccines against SARS-CoV-2 infection.
尽管人们已经付出了巨大的努力来阐明重症 COVID-19 病例的发病机制,但由于缺乏活检组织,占所有患者 90%的中度病例的详细机制仍不清楚。在这里,我们建立了 COVID-19 感染的食蟹猴模型(CMs),监测了临床和病理特征,并通过对 COVID-19 CMs 模型的肺组织和血清样本进行蛋白质组学和代谢组学分析,分析了早期感染阶段的潜在发病机制。我们的数据表明,固有免疫反应、中性粒细胞和血小板的激活在 COVID-19 CMs 中主要失调。在大多数受感染的 CMs 中,严重 COVID-19 患者的主要特征——中性粒细胞增多、淋巴细胞减少和大量“细胞因子风暴”的症状大大减弱,更类似于中度患者。因此,CMs 中的 COVID-19 模型合理地理解了中度 COVID-19 的发病机制,并且可能是评估针对 SARS-CoV-2 感染的治疗方法和疫苗安全性和疗效的候选模型。