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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

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

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

doi: 10.24272/j.issn.2095-8137.2020.202

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

Funds: This work was supported by the National Key Research and Development Program of China (2020YFC0842000)
More Information
  • 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。
    #Authors contributed equally to this work
  • Figure  1.  Establishment of SARS-CoV-2 infection model in ChRMs

    A: Characteristics of enrolled animals. B: Schematic of study design. C: Viral loads in nose, throat, and rectal swabs, and in tracheal brushes.

    Figure  2.  Clinical and pathological features of SARS-CoV-2-infected young and aged ChRMs

    A: Body weight and body temperature changes in SARS-CoV-2-infected macaques. B: Blood gas analysis of SARS-CoV-2-infected macaques. C: Number of immune cells in peripheral blood. D: SARS-CoV-2-specific antibodies in plasma. E: Viral loads in lung tissues. F: Gross lesions and H&E staining of lungs (Black arrow: Congestion in lung; Red arrow: Immune cell infiltration; Green arrow: Interstitial pneumonia). *: 0.01<P<0.05; **: 0.001<P≤0.01.

    Figure  3.  Immune responses in young and aged ChRMs during SARS-CoV-2 infection

    A: Concentrations of cytokines in plasma. B: Concentrations of cytokines in lung tissue. *: 0.01<P<0.05; **: 0.001<P≤0.01; ***: 0.0001<P≤0.001; ****: P≤0.0001.

    Figure  4.  Immunofluorescence staining of immune cells in lungs

    Figure  5.  Characteristics of CD4+ T and CD8+ T cells in peripheral blood (★: P<0.05)

  • [1] Brien JD, Uhrlaub JL, Hirsch A, Wiley CA, Nikolich-Žugich J. 2009. Key role of T cell defects in age-related vulnerability to West Nile virus. Journal of Experimental Medicine, 206(12): 2735−2745. doi:  10.1084/jem.20090222
    [2] Center for Disease Control and Prevention Weekly (American CDC). 2020. Severe outcomes among patients with coronavirus disease 2019 (COVID-19) — United States, February 12–March 16, 2020. Morbidity and Mortality Weekly Report, 69(12): 343−346. doi:  10.15585/mmwr.mm6912e2
    [3] Chan JFW, Yuan SF, Kok KH, To KKW, Chu H, Yang J, et al. 2020. A familial cluster of pneumonia associated with the 2019 novel coronavirus indicating person-to-person transmission: a study of a family cluster. The Lancet, 395(10223): 514−523. doi:  10.1016/S0140-6736(20)30154-9
    [4] Channappanavar R, Fehr AR, Vijay R, Mack M, Zhao JC, Meyerholz DK, et al. 2016. Dysregulated type I interferon and inflammatory monocyte-macrophage responses cause lethal pneumonia in SARS-CoV-infected mice. Cell Host & Microbe, 19(2): 181−193.
    [5] Channappanavar R, Fehr AR, Zheng J, Wohlford-Lenane C, Abrahante JE, Mack M, et al. 2019. IFN-I response timing relative to virus replication determines MERS coronavirus infection outcomes. The Journal of Clinical Investigation, 129(9): 3625−3639. doi:  10.1172/JCI126363
    [6] Chu H, Chan JFW, Wang YX, Yuen TTT, Chai Y, Hou YX, et al. 2020. Comparative replication and immune activation profiles of SARS-CoV-2 and SARS-CoV in human lungs: an ex vivo study with implications for the pathogenesis of COVID-19. Clinical Infectious Diseases. doi:  10.1093/cid/ciaa410.
    [7] Colman RJ. 2018. Non-human primates as a model for aging. Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease, 1864(9): 2733−2741. doi:  10.1016/j.bbadis.2017.07.008
    [8] Davidson S, Maini MK, Wack A. 2015. Disease-promoting effects of type I interferons in viral, bacterial, and coinfections. Journal of Interferon & Cytokine Research, 35(4): 252−264.
    [9] Franceschi C, Salvioli S, Garagnani P, de Eguileor, Monti D, Capri M. 2017. Immunobiography and the heterogeneity of immune responses in the elderly: a focus on inflammaging and trained immunity. Frontiers in Immunology, 8: 982. doi:  10.3389/fimmu.2017.00982
    [10] Fulop T, Larbi A, Dupuis G, Le Page A, Frost EH, Cohen AA, et al. 2017. Immunosenescence and inflamm-aging as two sides of the same coin: friends or foes?. Frontiers in Immunology, 8: 1960.
    [11] Gao WT, Tamin A, Soloff A, D'Aiuto L, Nwanegbo E, Robbins PD, Bellini WJ, et al. 2003. Effects of a SARS-associated coronavirus vaccine in monkeys. The Lancet, 362(9399): 1895−1896. doi:  10.1016/S0140-6736(03)14962-8
    [12] Haagmans BL, Kuiken T, Martina BE, Fouchier RAM, Rimmelzwaan GF, van Amerongen G, et al. 2004. Pegylated interferon-α protects type 1 pneumocytes against SARS coronavirus infection in macaques. Nature Medicine, 10(3): 290−293. doi:  10.1038/nm1001
    [13] Huang KJ, Su IJ, Theron M, Wu YC, Lai SK, Liu CC, et al. 2005. An interferon-γ-related cytokine storm in SARS patients. Journal of Medical Virology, 75(2): 185−194. doi:  10.1002/jmv.20255
    [14] Kai L, Chen Y, Lin RZ, Han KY. 2020. Clinical features of COVID-19 in elderly patients: a comparison with young and middle-aged patients. Journal of Infection, 80(6): e14−e18. doi:  10.1016/j.jinf.2020.03.005
    [15] Kovacs EJ, Boe DM, Boule LA, Curtis BJ. 2017. Inflammaging and the lung. Clinics in Geriatric Medicine, 33(4): 459−471. doi:  10.1016/j.cger.2017.06.002
    [16] Lau SKP, Lau CCY, Chan KH, Li CP, Chen HL, Jin DY, et al. 2013. Delayed induction of proinflammatory cytokines and suppression of innate antiviral response by the novel Middle East respiratory syndrome coronavirus: implications for pathogenesis and treatment. Journal of General Virology, 94(12): 2679−2690. doi:  10.1099/vir.0.055533-0
    [17] Law HKW, Cheung CY, Ng HY, Sia SF, Chan YO, Luk W, et al. 2005. Chemokine up-regulation in SARS-coronavirus-infected, monocyte-derived human dendritic cells. Blood, 106(7): 2366−2374. doi:  10.1182/blood-2004-10-4166
    [18] Lee JS, Park S, Jeong HW, Ahn JY, Choi SJ, Lee H, et al. 2020. Immunophenotyping of COVID-19 and influenza highlights the role of type I interferons in development of severe COVID-19. Science Immunology, 5(49): eabd1554. doi:  10.1126/sciimmunol.abd1554
    [19] López J, Perez-Rojo G, Noriega C, Carretero I, Velasco C, Martinez-Huertas JA, et al. 2020. Psychological well-being among older adults during the Covid-19 outbreak: a comparative study of the young-old and the old-old adults. International Psychogeriatrics. doi:  10.1017/S1041610220000964.
    [20] Lu SY, Zhao Y, Yu WH, Yang Y, Gao JH, Wang JB, et al. 2020. Comparison of SARS-CoV-2 infections among 3 species of non-human primates. bioRxiv. doi:  10.1101/2020.04.08.031807.
    [21] Mahbub S, Brubaker AL, Kovacs EJ. 2011. Aging of the innate immune system: an update. Current Immunology Reviews, 7(1): 104−115. doi:  10.2174/157339511794474181
    [22] McGonagle D, Sharif K, O'Regan A, Bridgewood C. 2020. The role of cytokines including interleukin-6 in COVID-19 induced pneumonia and macrophage activation syndrome-like disease. Autoimmunity Reviews, 19(6): 102537. doi:  10.1016/j.autrev.2020.102537
    [23] Mehta P, McAuley DF, Brown M, Sanchez E, Tattersall RS, Manson JJ, et al. 2020. COVID-19: consider cytokine storm syndromes and immunosuppression. The Lancet, 395(10229): 1033−1034. doi:  10.1016/S0140-6736(20)30628-0
    [24] Mikami T, Miyashita H, Yamada T, Harrington M, Steinberg D, Dunn A, et al. 2020. Risk factors for mortality in patients with COVID-19 in New York City. Journal of General Internal Medicine. doi:  10.1007/s11606-020-05983-z.
    [25] Munster VJ, Feldmann F, Williamson BN, van Doremalen N, Pérez-Pérez L, Schulz J, et al. 2020. Respiratory disease in rhesus macaques inoculated with SARS-CoV-2. Nature. doi:  10.1038/s41586-020-2324-7.
    [26] Ongrádi J, Kövesdi V. 2010. Factors that may impact on immunosenescence: an appraisal. Immunity & Ageing, 7: 7.
    [27] Park A, Iwasaki A. 2020. Type I and Type III Interferons - induction, signaling, evasion, and application to combat COVID-19. Cell Host & Microbe, 27(6): 870−878.
    [28] Pritchard GH, Kedl RM, Hunter CA. 2019. The evolving role of T-bet in resistance to infection. Nature Reviews Immunology, 19(6): 398−410. doi:  10.1038/s41577-019-0145-4
    [29] Rockx B, Baas T, Zornetze GA, Haagmans B, Sheahan T, Frieman M, et al. 2009. Early upregulation of acute respiratory distress syndrome-associated cytokines promotes lethal disease in an aged-mouse model of severe acute respiratory syndrome coronavirus infection. Journal of Virology, 83(14): 7062−7074. doi:  10.1128/JVI.00127-09
    [30] Ron-Harel N, Notarangelo G, Ghergurovich JM, Paulo JA, Sage PT, Santos D, et al. 2018. Defective respiration and one-carbon metabolism contribute to impaired naive T cell activation in aged mice. Proceedings of the National Academy of Sciences of the United States of America, 115(52): 13347−13352. doi:  10.1073/pnas.1804149115
    [31] Salam N, Rane S, Das R, Faulkner M, Gund R, Kandpal U, et al. 2013. T cell ageing: effects of age on development, survival & function. The Indian Journal of Medical Research, 138(5): 595−608.
    [32] Shan C, Yao YF, Yang XL, Zhou YW, Gao G, Peng Y, et al. 2020. Infection with novel coronavirus (SARS-CoV-2) causes pneumonia in Rhesus macaques. Cell Research. doi:  10.1038/s41422-020-0364-z.
    [33] Smith JS, Nicholson LT, Suwanpradid J, Glenn RA, Knape NM, Alagesan P, et al. 2018. Biased agonists of the chemokine receptor CXCR3 differentially control chemotaxis and inflammation. Science Signaling, 11(555): eaaq1075. doi:  10.1126/scisignal.aaq1075
    [34] Smithey MJ, Renkema KR, Rudd BD, Nikolich-Žugich J. 2011. Increased apoptosis, curtailed expansion and incomplete differentiation of CD8+ T cells combine to decrease clearance of L. monocytogenes in old mice. European Journal of Immunology, 41(5): 1352−1364. doi:  10.1002/eji.201041141
    [35] Smits SL, de Lang A, van den Brand JMA, Leijten LM, van IJcken WF, Eijkemans MJC, et al. 2010. Exacerbated innate host response to SARS-CoV in aged non-human primates. PLoS Pathogens, 6(2): e1000756. doi:  10.1371/journal.ppat.1000756
    [36] Stone SL, Peel JN, Scharer CD, Risley CA, Chisolm DA, Schultz MD, et al. 2019. T-bet transcription factor promotes antibody-secreting cell differentiation by limiting the inflammatory effects of IFN-γ on B cells. Immunity, 50(5): 1172−1187. doi:  10.1016/j.immuni.2019.04.004
    [37] Tang XL, Wu CC, Li X, Song YH, Yao XM, Wu XK, et al. 2020. On the origin and continuing evolution of SARS-CoV-2. National Science Review, 7(6): 1012−1023. doi:  10.1093/nsr/nwaa036
    [38] The Novel Coronavirus Pneumonia Emergency Response Epidemiology Team. 2020. The epidemiological characteristics of an outbreak of 2019 novel coronavirus diseases (COVID-19) —China, 2020. China CDC Weekly, 2(8): 113−122. doi:  10.46234/ccdcw2020.032
    [39] Trouillet-Assant S, Viel S, Gaymard A, Pons S, Richard JC, Perret M, et al. 2020. Type I IFN immunoprofiling in COVID-19 patients. The Journal of Allergy and Clinical Immunology, 146(1): 206−208. doi:  10.1016/j.jaci.2020.04.029
    [40] Wang C, Zheng XX, Gai WW, Zhao YK, Wang HL, Wang HJ, et al. 2017. MERS-CoV virus-like particles produced in insect cells induce specific humoural and cellular imminity in rhesus macaques. Oncotarget, 8(8): 12686−12694. doi:  10.18632/oncotarget.8475
    [41] Wang XH, Song TZ, Li L, Tian RR, Zheng YT. 2020. Successful implementation of intestinal resection and anastomosis in non-human primates suggests the possibility of longitudinal Intestinal research. Zoological Research, 41(4): 449−454. doi:  10.24272/j.issn.2095-8137.2020.049
    [42] Williamson EJ, Walker AJ, Bhaskaran K, Bacon S, Bates C, Morton CE, et al. 2020. OpenSAFELY: factors associated with COVID-19 death in 17 million patients. Nature. doi:  10.1038/s41586-020-2521-4.
    [43] Woolsey C, Borisevich V, Prasad AN, Agans KN, Deer DJ, Dobias NS, et al. 2020. Establishment of an African green monkey model for COVID-19. bioRxiv. doi:  10.1101/2020.05.17.100289.
    [44] World Health Organization (WHO). 2020. Coronavirus disease (COVID-19): Situation Report–175. Geneva: WHO.
    [45] Xu L, Yu DD, Ma YH, Yao YL, Luo RH, Feng XL, et al. 2020. COVID-19-like symptoms observed in Chinese tree shrews infected with SARS-CoV-2. Zoological Research, 41(5): 517−526. doi:  10.24272/j.issn.2095-8137.2020.053
    [46] Xu YS, Jia ZC, Zhou LY, Wang L, Li JT, Liang YF, et al. 2007. Evaluation of the safety, immunogenicity and pharmacokinetics of equine anti-SARS-CoV F(ab')2 in macaque. International Immunopharmacology, 7(13): 1834−1840. doi:  10.1016/j.intimp.2007.09.011
    [47] Yoshida K, Cologne JB, Cordova K, Misumi M, Yamaoka M, Kyoizumi S, et al. 2017. Aging-related changes in human T-cell repertoire over 20 years delineated by deep sequencing of peripheral T-cell receptors. Experimental Gerontology, 96: 29−37. doi:  10.1016/j.exger.2017.05.015
    [48] Yu P, Qi FF, Xu YF, Li FD, Liu PP, Liu JY, et al. 2020a. Age-related rhesus macaque models of COVID-19. Animal Models and Experimental Medicine, 3(1): 93−97. doi:  10.1002/ame2.12108
    [49] Yu WB, Tang GD, Zhang L, Corlett RT. 2020b. Decoding the evolution and transmissions of the novel pneumonia coronavirus (SARS-CoV-2 / HCoV-19) using whole genomic data. Zoological Research, 41(3): 247−257. doi:  10.24272/j.issn.2095-8137.2020.022
    [50] Yuki K, Fujiogi M, Koutsogiannaki S. 2020. COVID-19 pathophysiology: a review. Clinical Immunology, 215: 108427. doi:  10.1016/j.clim.2020.108427
    [51] Zhang LT, Tian RR, Zheng HY, Pan GQ, Tuo XY, Xia HJ, et al. 2016. Translocation of microbes and changes of immunocytes in the gut of rapid- and slow-progressor Chinese rhesus macaques infected with SIV mac239. Immunology, 147(4): 443−452. doi:  10.1111/imm.12574
    [52] Zhang MX, Song TZ, Zheng HY, Wang XH, Lu Y, Zhang HD, et al. 2019. Superior intestinal integrity and limited microbial translocation are associated with lower immune activation in SIVmac239-infected northern pig-tailed macaques (Macaca leonina). Zoological Research, 40(6): 522−531. doi:  10.24272/j.issn.2095-8137.2019.047
    [53] Zhang XL, Pang W, Hu XT, Li JL, Yao YG, Zheng YT. 2014. Experimental primates and non-human primate (NHP) models of human diseases in China: Current status and progress. Zoological Research, 35(6): 447−464.
    [54] Zhao MM, Wang ML, Zhang JS, Gu J, Zhang PA, Xu Y, et al. 2020. Comparison of clinical characteristics and outcomes of patients with coronavirus disease 2019 at different ages. Aging, 12(11): 10070−10086. doi:  10.18632/aging.103298
    [55] Zheng HY, Zhang M, Yang CX, Zhang N, Wang XC, Yang XP, et al. 2020. Elevated exhaustion levels and reduced functional diversity of T cells in peripheral blood may predict severe progression in COVID-19 patients. Cellular & Molecular Immunology, 17(5): 541−543.
    [56] Zheng HY, Zhang MX, Pang W, Zheng YT. 2014. Aged Chinese rhesus macaques suffer severe phenotypic T- and B-cell aging accompanied with sex differences. Experimental Gerontology, 55: 113−119. doi:  10.1016/j.exger.2014.04.004
    [57] Zhu TT, Wang YJ, Zhou SC, Zhang N, Xia LM. 2020. A comparative study of chest computed tomography features in young and older adults with corona virus disease (COVID-19). Journal of Thoracic Imaging, 35(4): W97−W101. doi:  10.1097/RTI.0000000000000513
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  • 收稿日期:  2020-07-22
  • 录用日期:  2020-07-30
  • 网络出版日期:  2020-08-06
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