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

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

doi:10.24272/j.issn.2095-8137.2020.202

Volume 41 Issue 5

Sep. 2020

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Article Navigation > Zoological Research > 2020 > 41(5): 503-516

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. Delayed severe cytokine storm and immune cell infiltration in SARS-CoV-2-infected aged Chinese rhesus macaques. Zoological Research, 2020, 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. Delayed severe cytokine storm and immune cell infiltration in SARS-CoV-2-infected aged Chinese rhesus macaques. Zoological Research, 2020, 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. Delayed severe cytokine storm and immune cell infiltration in SARS-CoV-2-infected aged Chinese rhesus macaques. Zoological Research, 2020, 41(5): 503-516. doi: 10.24272/j.issn.2095-8137.2020.202

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

doi: 10.24272/j.issn.2095-8137.2020.202

Tian-Zhang Song^{1, 2, #},
Hong-Yi Zheng^{1, 2, #},
Jian-Bao Han^{2, #},
Lin Jin^{1, 2, #},
Xiang Yang²,
Feng-Liang Liu¹,
Rong-Hua Luo¹,
Ren-Rong Tian¹,
Hou-Rong Cai³,
Xiao-Li Feng²,
Chao Liu⁴,
Ming-Hua Li^{2, 4},
Yong-Tang Zheng^{1, 2, 4
,
,}

1.
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
2.
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
3.
Department of Respiratory and Critical Care Medicine, Affiliated Drum Tower Hospital of Nanjing University, Nanjing, Jiangsu 210008, China
4.
National Resource Center for Non-Human Primates, National Research Facility for Phenotypic & Genetic Analysis of Model Animals (Primate Facility), Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, Yunnan 650107, China

#Authors contributed equally to this work

Funds: This work was supported by the National Key Research and Development Program of China (2020YFC0842000)

More Information

Corresponding author: E-mail: zhengyt@mail.kiz.ac.cn
Received Date: 2020-07-22
Accepted Date: 2020-07-30

Published Online: 2020-08-06

Publish Date: 2020-09-18

Abstract

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.
- COVID-19,
- Non-human primate animal model,
- Elderly,
- Immune response

#Authors contributed equally to this work

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References(57)

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