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宋天章, 郑宏毅, 韩建保, 靳林, 杨翔, 刘丰亮, 罗荣华, 田仁荣, 蔡后荣, 冯小丽, 刘超, 李明华, 郑永唐. 2020: SARS-CoV-2感染老年中国猕猴呈现迟发且严重的细胞因子风暴和免疫细胞浸润. 动物学研究, 41(5): 503-516. DOI: 10.24272/j.issn.2095-8137.2020.202
引用本文: 宋天章, 郑宏毅, 韩建保, 靳林, 杨翔, 刘丰亮, 罗荣华, 田仁荣, 蔡后荣, 冯小丽, 刘超, 李明华, 郑永唐. 2020: SARS-CoV-2感染老年中国猕猴呈现迟发且严重的细胞因子风暴和免疫细胞浸润. 动物学研究, 41(5): 503-516. DOI: 10.24272/j.issn.2095-8137.2020.202
Tian-Zhang Song, Hong-Yi Zheng, Jian-Bao Han, Lin Jin, Xiang Yang, Feng-Liang Liu, Rong-Hua Luo, Ren-Rong Tian, Hou-Rong Cai, Xiao-Li Feng, Chao Liu, Ming-Hua Li, Yong-Tang Zheng. 2020. Delayed severe cytokine storm and immune cell infiltration in SARS-CoV-2-infected aged Chinese rhesus macaques. Zoological Research, 41(5): 503-516. DOI: 10.24272/j.issn.2095-8137.2020.202
Citation: Tian-Zhang Song, Hong-Yi Zheng, Jian-Bao Han, Lin Jin, Xiang Yang, Feng-Liang Liu, Rong-Hua Luo, Ren-Rong Tian, Hou-Rong Cai, Xiao-Li Feng, Chao Liu, Ming-Hua Li, Yong-Tang Zheng. 2020. Delayed severe cytokine storm and immune cell infiltration in SARS-CoV-2-infected aged Chinese rhesus macaques. Zoological Research, 41(5): 503-516. DOI: 10.24272/j.issn.2095-8137.2020.202

SARS-CoV-2感染老年中国猕猴呈现迟发且严重的细胞因子风暴和免疫细胞浸润

Delayed severe cytokine storm and immune cell infiltration in SARS-CoV-2-infected aged Chinese rhesus macaques

  • 摘要: 截至2020年6月,全球新型冠状病毒感染者死亡人数已增至44万人,死亡患者中年龄大于65岁的老年人约占74%。因此,高龄是目前公认的新型冠状病毒感染死亡最重要风险因素。本研究通过构建老年及青年中国猕猴新型冠状病毒感染疾病模型,分析年龄对新型冠状病毒感染疾病进程的影响。结果表明,青年猕猴在感染后第1周表现为呼吸功能受损、肺部病毒活跃复制、肺部严重病理损伤以及肺组织中CD11b+ 细胞和CD8+ T细胞浸润,但在感染第2周疾病特征迅速恢复。与之相比,老年猕猴在感染第2周表现出明显的免疫反应和严重的细胞因子风暴,肺部CD11b+ 细胞浸润增加并伴有CD8+ T细胞持续浸润。同时,老年猕猴外周血T细胞显示出比年轻猕猴更明显的趋化性,但其抗病毒功能较弱。因此,延迟但更严重的细胞因子风暴和免疫细胞浸润可能是老年新型冠状病毒感染者预后不良的原因。

     

    Abstract: 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 (Macaca mulatta) 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.

     

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