Key Laboratory of Animal Models and Human Disease Mechanisms of the Chinese Academy of Sciences, KIZ-CUHK Joint Laboratory of Bioresources and Molecular Research in Common Diseases, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, Yunnan 650223, China.
Kunming National High-Level Biosafety Research Center for Non-Human Primates, Center for Biosafety Mega-Science, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, Yunnan 650107, China.
Zool Res. 2020 Sep 18;41(5):503-516. doi: 10.24272/j.issn.2095-8137.2020.202.
As of June 2020, Coronavirus Disease 2019 (COVID-19) has killed an estimated 440 000 people worldwide, 74% of whom were aged ≥65 years, making age the most significant risk factor for death caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. To examine the effect of age on death, we established a SARS-CoV-2 infection model in Chinese rhesus macaques ( ) of varied ages. Results indicated that infected young macaques manifested impaired respiratory function, active viral replication, severe lung damage, and infiltration of CD11b and CD8 cells in lungs at one-week post infection (wpi), but also recovered rapidly at 2 wpi. In contrast, aged macaques demonstrated delayed immune responses with a more severe cytokine storm, increased infiltration of CD11b cells, and persistent infiltration of CD8 cells in the lungs at 2 wpi. In addition, peripheral blood T cells from aged macaques showed greater inflammation and chemotaxis, but weaker antiviral functions than that in cells from young macaques. Thus, the delayed but more severe cytokine storm and higher immune cell infiltration may explain the poorer prognosis of older aged patients suffering SARS-CoV-2 infection.
截至 2020 年 6 月,全球范围内估计有 44 万人死于 2019 年冠状病毒病(COVID-19),其中 74%的患者年龄≥65 岁,这表明年龄是由严重急性呼吸综合征冠状病毒 2(SARS-CoV-2)感染引起的死亡的最重要危险因素。为了研究年龄对死亡的影响,我们建立了一个年龄不同的中国猕猴( )的 SARS-CoV-2 感染模型。结果表明,感染后的年轻猕猴在感染后一周(wpi)表现出呼吸功能受损、病毒复制活跃、肺部严重损伤以及 CD11b 和 CD8 细胞浸润,但在 2wpi 时也迅速恢复。相比之下,老年猕猴表现出延迟的免疫反应,伴有更严重的细胞因子风暴,在 2wpi 时 CD11b 细胞浸润增加,CD8 细胞持续浸润肺部。此外,来自老年猕猴的外周血 T 细胞表现出更强的炎症和趋化性,但抗病毒功能比年轻猕猴的细胞弱。因此,延迟但更严重的细胞因子风暴和更高的免疫细胞浸润可能解释了 SARS-CoV-2 感染的老年患者预后较差的原因。