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Delayed severe cytokine storm and immune cell infiltration in SARS-CoV-2-infected aged Chinese rhesus macaques.
Zool Res. 2020 Sep 18; 41(5):503-516.ZR

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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Authors+Show Affiliations

Song TZ
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.
Zheng HY
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.
Han JB
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.
Jin L
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.
Yang X
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.
Liu FL
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.
Luo RH
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.
Tian RR
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.
Cai HR
Department of Respiratory and Critical Care Medicine, Affiliated Drum Tower Hospital of Nanjing University, Nanjing, Jiangsu 210008, China.
Feng XL
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.
Liu C
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.
Li MH
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. 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.
Zheng YT
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. 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. E-mail: zhengyt@mail.kiz.ac.cn.

MeSH

Age FactorsAgingAnimalsBetacoronavirusCOVID-19Coronavirus InfectionsCytokinesInflammationLungMacaca mulattaMonkey DiseasesPandemicsPneumonia, ViralSARS-CoV-2Severe Acute Respiratory SyndromeT-LymphocytesViral LoadVirus Replication

Pub Type(s)

Journal Article

Language

eng

PubMed ID

32772513

Citation

Song, Tian-Zhang, et al. "Delayed Severe Cytokine Storm and Immune Cell Infiltration in SARS-CoV-2-infected Aged Chinese Rhesus Macaques." Zoological Research, vol. 41, no. 5, 2020, pp. 503-516.
Song TZ, Zheng HY, Han JB, et al. Delayed severe cytokine storm and immune cell infiltration in SARS-CoV-2-infected aged Chinese rhesus macaques. Zool Res. 2020;41(5):503-516.
Song, T. Z., Zheng, H. Y., Han, J. B., Jin, L., Yang, X., Liu, F. L., Luo, R. H., Tian, R. R., Cai, H. R., Feng, X. L., Liu, C., Li, M. H., & Zheng, Y. T. (2020). Delayed severe cytokine storm and immune cell infiltration in SARS-CoV-2-infected aged Chinese rhesus macaques. Zoological Research, 41(5), 503-516. https://doi.org/10.24272/j.issn.2095-8137.2020.202
Song TZ, et al. Delayed Severe Cytokine Storm and Immune Cell Infiltration in SARS-CoV-2-infected Aged Chinese Rhesus Macaques. Zool Res. 2020 Sep 18;41(5):503-516. PubMed PMID: 32772513.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Delayed severe cytokine storm and immune cell infiltration in SARS-CoV-2-infected aged Chinese rhesus macaques. AU - Song,Tian-Zhang, AU - Zheng,Hong-Yi, AU - Han,Jian-Bao, AU - Jin,Lin, AU - Yang,Xiang, AU - Liu,Feng-Liang, AU - Luo,Rong-Hua, AU - Tian,Ren-Rong, AU - Cai,Hou-Rong, AU - Feng,Xiao-Li, AU - Liu,Chao, AU - Li,Ming-Hua, AU - Zheng,Yong-Tang, PY - 2020/8/11/pubmed PY - 2020/9/8/medline PY - 2020/8/11/entrez KW - COVID-19 KW - Elderly KW - Immune response KW - Non-human primate animal model SP - 503 EP - 516 JF - Zoological research JO - Zool Res VL - 41 IS - 5 N2 - 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. SN - 2095-8137 UR - https://www.unboundmedicine.com/medline/citation/32772513/Delayed_severe_cytokine_storm_and_immune_cell_infiltration_in_SARS_CoV_2_infected_aged_Chinese_rhesus_macaques_ DB - PRIME DP - Unbound Medicine ER -