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COVID-19-like symptoms observed in Chinese tree shrews infected with SARS-CoV-2

Ling Xu Dan-Dan Yu Yu-Hua Ma Yu-Lin Yao Rong-Hua Luo Xiao-Li Feng Hou-Rong Cai Jian-Bao Han Xue-Hui Wang Ming-Hua Li Chang-Wen Ke Yong-Tang Zheng Yong-Gang Yao

Ling Xu, Dan-Dan Yu, Yu-Hua Ma, Yu-Lin Yao, Rong-Hua Luo, Xiao-Li Feng, Hou-Rong Cai, Jian-Bao Han, Xue-Hui Wang, Ming-Hua Li, Chang-Wen Ke, Yong-Tang Zheng, Yong-Gang Yao. COVID-19-like symptoms observed in Chinese tree shrews infected with SARS-CoV-2. Zoological Research, 2020, 41(5): 517-526. doi: 10.24272/j.issn.2095-8137.2020.053
Citation: Ling Xu, Dan-Dan Yu, Yu-Hua Ma, Yu-Lin Yao, Rong-Hua Luo, Xiao-Li Feng, Hou-Rong Cai, Jian-Bao Han, Xue-Hui Wang, Ming-Hua Li, Chang-Wen Ke, Yong-Tang Zheng, Yong-Gang Yao. COVID-19-like symptoms observed in Chinese tree shrews infected with SARS-CoV-2. Zoological Research, 2020, 41(5): 517-526. doi: 10.24272/j.issn.2095-8137.2020.053

SARS-CoV-2感染中国树鼩呈现COVID-19样症状

doi: 10.24272/j.issn.2095-8137.2020.053

COVID-19-like symptoms observed in Chinese tree shrews infected with SARS-CoV-2

Funds: This work was partly supported by the National Key R&D Program of China (2020YFC0842000 to Y.T.Z.), National Natural Science Foundation of China (U1902215 to Y.G.Y.), National Science and Technology Major Projects of Infectious Disease Funds (2017ZX10304402 to Y.T.Z.), Yunnan Province (2018FB046 to D.D.Y.), and CAS “Light of West China” Program (xbzg-zdsys-201909 to Y.G.Y. and Y.T.Z.)
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  • 摘要: 2019冠状病毒病(COVID-19)大流行对全球公共卫生安全构成了巨大威胁。找到易感染新型冠状病毒(SARS-CoV-2/HCoV-19)的实验动物对于控制疫情、筛选有效的预防或治疗方法都是至关重要的。在本研究中,我们对灵长动物近亲——树鼩进行了新型冠状病毒感染模型创建研究。我们选择了不同年龄段的树鼩,包括1岁左右的成年树鼩和5-6岁的老年树鼩,感染SARS-CoV-2。在树鼩接种病毒后的不同天数进行肺部影像学、病毒载量、血常规和生化以及组织病理学等分析。结果表明,树鼩可以感染SARS-CoV-2病毒。X射线检查可以在大多数感染树鼩看到肺部浸润。在感染后3、5和7天,感染树鼩肺组织中可检测到病毒RNA,血常规和血清生化相关参数也发生变化,包括天冬氨酸转氨酶(AST)和尿素氮(BUN)水平升高。感染后3天成年组和7天老年组树鼩肺组织病理学染色显示肺泡间隔增厚,间质出血。在病毒排出高峰方面,两个不同的年龄组中存在一些差异。我们的研究结果表明,中国树鼩有可能成为COVID-19机制研究、药物和疫苗评价的模型动物。
    #Authors contributed equally to this work
  • Figure  1.  Schematic of experimental design

    Tree shrews were divided into two groups, i.e., adult group (n=13, black circles) and old group (n=7, red circles), and inoculated with SARS-CoV-2 (black triangle) via intranasal, ocular, and oral routes. At 0, 3, 5, 7, 11 (old group), or 14 (adult group) days post-inoculation (dpi), clinical examinations were performed to show tree shrew status. Animals from each group were euthanized and necropsied at indicated dpi for virological and pathological assays.

    Figure  2.  Chest X-rays of tree shrews before and after SARS-CoV-2 inoculation

    Circled areas on radiographs are regions showing lung infiltrates.

    Figure  3.  Viral loads of SARS-CoV-2 in Chinese tree shrews

    Viral loads in serum and throat/rectal swabs (A), lung lobes (B), and other tissues (C) from infected tree shrews measured using quantitative real-time PCR. Each graphic represents one individual, with color referring to indicated dpi. For instance, three infected animals sacrificed at 3 dpi were defined by square, circle, and diamond, respectively. Marks in blue refer to time point 3 dpi.

    Figure  4.  Characterization of lung changes after SARS-CoV-2 infection in Chinese tree shrews

    A: Lesions in lungs. Representative view of ventral lungs of infected tree shrew obtained via necropsy at 3 dpi in adult group or at 7dpi in old group compared to healthy control. White box indicates lungs showing focal areas of hyperemia. B, C: Representative hematoxylin and eosin staining (B) and immunofluorescence analysis of viral antigen NP (C) in lung tissues from tree shrews at 3 dpi in adult group or at 7 dpi in old group. Blue arrows in A refer to lesions. Yellow arrows in B indicate pulmonary lymphocytes or neutrophils. White arrows in C indicate SARS-CoV-2 NP staining (green) in pneumocytes, with DAPI staining in blue. PBS and IgG indicate tissue sample from healthy animal in control group treated with PBS but no SARS-CoV-2. Scale bars: 100 µm.

    Figure  5.  Laboratory findings of altered blood counts (A) and serum biochemistry (B) in tree shrews before and after SARS-CoV-2 infection

    Values are means±SD. P-values were calculated using paired Student’s t test. Each circle represents one individual, with “Before” and “After” referring to indicated parameter in same animal before SARS-CoV-2 infection and at time of euthanasia, respectively. We grouped all infected animals in each group together, regardless of different infection times of different animals.

    Table  1.   Laboratory findings of adult tree shrews infected with SARS-CoV-2

    ParameterBefore inoculation (13/13, 100%)After inoculation
    Total (13/13, 100%)P-valuea3 dpi (3/13, 23%)5 dpi (3/13, 23%)7 dpi (3/13, 23%)14 dpi (4/13, 31%)
    White blood cell count (×109/L)1.80±1.124.85±3.330.00171.37±0.703.83±1.253.77±2.208.75±2.62
    Lymphocyte count (×109/L)0.85±0.431.34±0.510.02300.70±0.462.27±0.901.83±0.711.50±0.37
    Monocyte count (×109/L)0.18±0.090.38±0.230.01760.27±0.210.47±0.120.50±0.440.33±0.05
    Granulocyte count (×109/L)0.62±0.461.75±1.160.00280.80±0.701.10±0.361.43±1.103.18±0.14
    Lymphocyte percentage (%)52.64±10.6951.09±7.860.692043.90±5.7259.00±4.1552.30±10.7049.65±4.38
    Monocyte percentage (%)13.36±3.9210.55±4.710.172714.57±1.1712.63±3.7711.67±4.015.15±2.63
    Granulocyte percentage (%)34.40±9.0233.65±7.160.917541.53±4.5628.37±2.3036.03±8.4729.93±5.07
    BUN (mg/dL)16.46±4.1823.65±8.430.019626.00±8.1923.00±6.2516.67±11.0627.50±7.59
    TP (g/dL)6.56±0.286.40±0.770.48905.57±0.386.13±0.906.87±0.466.88±0.57
    ALB (g/dL)3.74±0.443.20±0.650.01342.50±0.262.97±0.353.60±0.463.60±0.71
    Globulin (g/dL)2.82±0.273.17±0.260.00443.07±0.153.17±0.553.23±0.123.20±0.16
    ALT (U/L)151.10±79.21187.80±123.400.2662141.70±80.59138.3±77.69247.70±55.77214.50±203.40
    AST (U/L)197.00±44.99467.80±286.200.0035238.30±73.35583.30±227.00363.30±75.22631.50±415.20
    a: P-values indicate differences before and after inoculation (total). P<0.05 was considered statistically significant. Data are means±SD (Test No./ Total No., %). Paired Student’s t test.
    BUN: Blood urea nitrogen, TP: Total protein, ALB: Albumin, ALT: Alanine aminotransferase, AST: Aspartate aminotransferase.
    下载: 导出CSV

    Table  2.   Laboratory findings of old tree shrews infected with SARS-CoV-2

    ParameterBefore inoculation (7/7, 100%)After inoculation
    Total (7/7, 100%)P-valuea3 dpi (2/7, 28%)5 dpi (2/7, 28%)7 dpi (2/7, 28%)14 dpi (1/7, 14%)
    White blood cell count (×109/L)1.45±0.533.12±2.250.07540.80±0.286.05±0.492.75±1.342.90
    Lymphocyte count (×109/L)0.45±0.261.67±1.680.11010.65±0.493.2±2.261.85±0.210.30
    Monocyte count (×109/L)0.21±0.070.20±0.160.83470.05±0.070.35±0.210.25±0.070.10
    Granulocyte count (×109/L)0.77±0.311.014±0.950.53200.50±0.280.50±0. 281.05±0.493.00
    Lymphocyte percentage (%)30.77±11.7846.47±19.900.097744±8.3456.80±37.3451.2±3.1122.30
    Monocyte percentage (%)16.53±4.198.41±2.520.00098.75±1.625.70±2.829.10±0.4211.80
    Granulocyte percentage) (%)50.01±7.8547.23±22.050.758354.25±16.6247.9±49.2139.70±2.6846.90
    BUN (mg/dL)19.83±5.4431.29±11.510.008736.50±6.3643.00±4.2421.5±3.5317.00
    TP (g/dL)6.42±0.365.74±0.790.02005.45±1.065.55±0.926.50±0.285.20
    ALB (g/dL)3.26±0.352.50±0.550.00172.40±0.852.35±0.492.95±0.492.10
    Globulin (g/dL)3.13±0.213.25±0.290.30803.05±0.213.2±0.423.55±.0213.20
    ALT (U/L)202.40±77.66180.90±122.700.6428187.00±86.27115.50±33.23264.50±238.30132.00
    AST (U/L)229.00±31.97361.30±316.200.1606192.00±42.43271.00±183.80657.50±556.50288.00
    a: P-values indicate differences before and after inoculation (total). P<0.05 was considered statistically significant. Data are means±SD (Test No./ Total No., %). Paired Student’s t test.
    BUN: Blood urea nitrogen, TP: Total protein, ALB: Albumin, ALT: Alanine aminotransferase, AST: Aspartate aminotransferase.
    下载: 导出CSV
  • [1] Amako Y, Tsukiyama-Kohara K, Katsume A, Hirata Y, Sekiguchi S, Tobita Y, et al. 2010. Pathogenesis of hepatitis C virus infection in Tupaia belangeri. Journal of Virology, 84(1): 303−311. doi:  10.1128/JVI.01448-09
    [2] Bao LL, Deng W, Huang BY, Gao H, Liu JN, Ren LL, et al. 2020. The pathogenicity of SARS-CoV-2 in hACE2 transgenic mice. Nature. doi:  10.1038/s41586-020-2312-y.
    [3] Chan JFW, Zhang AJ, Yuan SF, Poon VKM, Chan CCS, Lee ACY, et al. 2020. Simulation of the clinical and pathological manifestations of Coronavirus Disease 2019 (COVID-19) in golden Syrian hamster model: implications for disease pathogenesis and transmissibility. Clinical Infectious Diseases. doi:  10.1093/cid/ciaa325.
    [4] Duan K, Liu BD, Li CS, Zhang HJ, Yu T, Qu JM, et al. 2020. Effectiveness of convalescent plasma therapy in severe COVID-19 patients. Proceedings of the National Academy of Sciences of the United States of America, 117(17): 9490−9496. doi:  10.1073/pnas.2004168117
    [5] Fan Y, Ye MS, Zhang JY, Xu L, Yu DD, Gu TL, et al. 2019. Chromosomal level assembly and population sequencing of the Chinese tree shrew genome. Zoological Research, 40(6): 506−521. doi:  10.24272/j.issn.2095-8137.2019.063
    [6] Gao Q, Bao LL, Mao HY, Wang L, Xu KW, Yang M, et al. 2020. Development of an inactivated vaccine candidate for SARS-CoV-2. Science, 369(6499): 77−81. doi:  10.1126/science.abc1932
    [7] Geleris J, Sun YF, Platt J, Zucker J, Baldwin M, Hripcsak G, et al. 2020. Observational study of hydroxychloroquine in hospitalized patients with COVID-19. The New England Journal of Medicine, 382(25): 2411−2418. doi:  10.1056/NEJMoa2012410
    [8] Goldman JD, Lye DCB, Hui DS, Marks KM, Bruno R, Montejano R, et al. 2020. Remdesivir for 5 or 10 days in patients with severe COVID-19. The New England Journal of Medicine. doi:  10.1056/NEJMoa2015301.
    [9] Grein J, Ohmagari N, Shin D, Diaz G, Asperges E, Castagna A, et al. 2020. Compassionate use of remdesivir for patients with severe COVID-19. The New England Journal of Medicine, 382(24): 2327−2336. doi:  10.1056/NEJMoa2007016
    [10] Guan WJ, Ni ZY, Hu Y, Liang WH, Ou CQ, He JX, et al. 2020. Clinical characteristics of coronavirus disease 2019 in China. The New England Journal of Medicine, 382(18): 1708−1720. doi:  10.1056/NEJMoa2002032
    [11] Kim YI, Kim SG, Kim SM, Kim EH, Park SJ, Yu KM, et al. 2020. Infection and rapid transmission of SARS-CoV-2 in ferrets. Cell Host Microbe, 27(5): 704−709.e2. doi:  10.1016/j.chom.2020.03.023
    [12] Lagier JC, Million M, Gautret P, Colson P, Cortaredona S, Giraud-Gatineau A, et al. 2020. Outcomes of 3, 737 COVID-19 patients treated with hydroxychloroquine/azithromycin and other regimens in Marseille, France: A retrospective analysis. Travel Medicine and Infectious Disease. doi:  10.1016/j.tmaid.2020.101791.
    [13] Lam TTY, Jia N, Zhang YW, Shum MHH, Jiang JF, Zhu HC, et al. 2020. Identifying SARS-CoV-2-related coronaviruses in Malayan pangolins. Nature. doi:  10.1038/s41586-020-2169-0.
    [14] Li LH, Li ZR, Wang EL, Yang R, Xiao Y, Han HB, et al. 2016. Herpes simplex virus 1 infection of tree shrews differs from that of mice in the severity of acute infection and viral transcription in the peripheral nervous system. Journal of Virology, 90(2): 790−804. doi:  10.1128/JVI.02258-15
    [15] Li RF, Zanin M, Xia XS, Yang ZF. 2018. The tree shrew as a model for infectious diseases research. Journal of Thoracic Disease, 10(Suppl 19): S2272−S2279.
    [16] Lu RJ, Zhao X, Li J, Niu PH, Yang B, Wu HL, et al. 2020a. Genomic characterisation and epidemiology of 2019 novel coronavirus: implications for virus origins and receptor binding. The Lancet, 395(10224): 565−574. doi:  10.1016/S0140-6736(20)30251-8
    [17] Lu SY, Zhao Y, Yu WH, Yang Y, Gao JH, Wang JB, et al. 2020b. Comparison of SARS-CoV-2 infections among 3 species of non-human primates. bioRxiv. doi:  10.1101/2020.04.08.031807.
    [18] Million M, Lagier JC, Gautret P, Colson P, Fournier PE, Amrane S, et al. 2020. Early treatment of COVID-19 patients with hydroxychloroquine and azithromycin: A retrospective analysis of 1061 cases in Marseille, France. Travel Medicine and Infectious Disease, 35: 101738. doi:  10.1016/j.tmaid.2020.101738
    [19] 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.
    [20] Reed LJ, Muench H. 1938. A simple method of estimating fifty per cent endpoints. American Journal of Epidemiology, 27(3): 493−497. doi:  10.1093/oxfordjournals.aje.a118408
    [21] Rockx B, Kuiken T, Herfst S, Bestebroer T, Lamers MM, Oude Munnink BB, et al. 2020. Comparative pathogenesis of COVID-19, MERS, and SARS in a nonhuman primate model. Science, 368(6494): 1012−1015. doi:  10.1126/science.abb7314
    [22] 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.
    [23] Shi JZ, Wen Z, Zhong GX, Yang HL, Wang C, Huang BY, et al. 2020. Susceptibility of ferrets, cats, dogs, and other domesticated animals to SARS-coronavirus 2. Science, 368(6494): 1016−1020. doi:  10.1126/science.abb7015
    [24] Tang W, Cao ZJ, Han MF, Wang ZY, Chen JW, Sun WJ, et al. 2020. Hydroxychloroquine in patients with mainly mild to moderate coronavirus disease 2019: open label, randomised controlled trial. BMJ: British Medical Journal, 369: m1849.
    [25] Wang DW, Hu B, Hu C, Zhu FF, Liu X, Zhang J, et al. 2020a. Clinical characteristics of 138 hospitalized patients with 2019 novel Coronavirus-infected pneumonia in Wuhan, China. JAMA. doi:  10.1001/jama.2020.1585.
    [26] Wang ML, Cao RY, Zhang LK, Yang XL, Liu J, Xu MY, et al. 2020b. Remdesivir and chloroquine effectively inhibit the recently emerged novel coronavirus (2019-nCoV) in vitro. Cell Research, 30(3): 269−271. doi:  10.1038/s41422-020-0282-0
    [27] Wang Q, Schwarzenberger P, Yang F, Zhang JJ, Su JJ, Yang C, et al. 2012. Experimental chronic hepatitis B infection of neonatal tree shrews (Tupaia belangeri chinensis): a model to study molecular causes for susceptibility and disease progression to chronic hepatitis in humans. Virology Journal, 9: 170. doi:  10.1186/1743-422X-9-170
    [28] Wang YM, Zhang DY, Du GH, Du RH, Zhao JP, Jin Y, et al. 2020c. Remdesivir in adults with severe COVID-19: a randomised, double-blind, placebo-controlled, multicentre trial. The Lancet, 395(10236): 1569−1578. doi:  10.1016/S0140-6736(20)31022-9
    [29] Williamson BN, Feldmann F, Schwarz B, Meade-White K, Porter DP, Schulz J, et al. 2020. Clinical benefit of remdesivir in rhesus macaques infected with SARS-CoV-2. Nature. doi:  10.1038/s41586-020-2423-5.
    [30] Wong G, Bi YH, Wang QH, Chen XW, Zhang ZG, Yao YG. 2020. Zoonotic origins of human coronavirus 2019 (HCoV-19/SARS-CoV-2): why is this work important?. Zoological Research, 41(3): 213−219. doi:  10.24272/j.issn.2095-8137.2020.031
    [31] Wu F, Zhao S, Yu B, Chen YM, Wang W, Song ZG, et al. 2020. A new coronavirus associated with human respiratory disease in China. Nature, 579(7798): 265−269. doi:  10.1038/s41586-020-2008-3
    [32] Xiao J, Liu R, Chen CS. 2017. Tree shrew (Tupaia belangeri) as a novel laboratory disease animal model. Zoological Research, 38(3): 127−137. doi:  10.24272/j.issn.2095-8137.2017.033
    [33] Xiao KP, Zhai JQ, Feng YY, Zhou N, Zhang X, Zou JJ, et al. 2020. Isolation of SARS-CoV-2-related coronavirus from Malayan pangolins. Nature, 583(7815): 286−289. doi:  10.1038/s41586-020-2313-x
    [34] Xu S, Li XY, Yang JY, Wang ZX, Jia Y, Han L, et al. 2019. Comparative pathogenicity and transmissibility of pandemic H1N1, avian H5N1, and human H7N9 influenza viruses in tree shrews. Frontiers in Microbiology, 10: 2955. doi:  10.3389/fmicb.2019.02955
    [35] Xu XL, Han MF, Li TT, Sun W, Wang DS, Fu BQ, et al. 2020. Effective treatment of severe COVID-19 patients with tocilizumab. Proceedings of the National Academy of Sciences of the United States of America, 117(20): 10970−10975. doi:  10.1073/pnas.2005615117
    [36] Yang XB, Yu Y, Xu JQ, Shu HQ, Xia JA, Liu H, et al. 2020. Clinical course and outcomes of critically ill patients with SARS-CoV-2 pneumonia in Wuhan, China: a single-centered, retrospective, observational study. The Lancet Respiratory Medicine, 8(5): 475−481. doi:  10.1016/S2213-2600(20)30079-5
    [37] Yao YG. 2017. Creating animal models, why not use the Chinese tree shrew (Tupaia belangeri chinensis)?. Zoological Research, 38(3): 118−126. doi:  10.24272/j.issn.2095-8137.2017.032
    [38] Yu B, Li CZ, Chen P, Zhou N, Wang LY, Li J, et al. 2020a. Low dose of hydroxychloroquine reduces fatality of critically ill patients with COVID-19. Science China Life Sciences. doi:  10.1007/s11427-020-1732-2.
    [39] Yu P, Qi FF, Xu YF, Li FD, Liu PP, Liu JY, et al. 2020b. Age-related rhesus macaque models of COVID-19. Animal Models and Experimental Medicine, 3(1): 93−97. doi:  10.1002/ame2.12108
    [40] Zhang C, Shi L, Wang FS. 2020a. Liver injury in COVID-19: management and challenges. The Lancet Gastroenterology & Hepatology, 5(5): 428−430.
    [41] 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
    [42] Zhang T, Wu QF, Zhang ZG. 2020b. Probable pangolin origin of SARS-CoV-2 associated with the COVID-19 outbreak. Current Biology, 30(7): 1346−1351.e2. doi:  10.1016/j.cub.2020.03.022
    [43] Zhao Y, Wang JB, Kuang DX, Xu JW, Yang ML, Ma CX, et al. 2020. Susceptibility of tree shrew to SARS-CoV-2 infection. bioRxiv. doi:  10.1101/2020.04.30.029736.
    [44] Zhou H, Chen X, Hu T, Li J, Song H, Liu YR, et al. 2020a. A novel bat coronavirus closely related to SARS-CoV-2 contains natural insertions at the S1/S2 cleavage site of the spike protein. Current Biology, 30(11): 2196−2203.e3. doi:  10.1016/j.cub.2020.05.023
    [45] Zhou P, Yang XL, Wang XG, Hu B, Zhang L, Zhang W, et al. 2020b. A pneumonia outbreak associated with a new coronavirus of probable bat origin. Nature, 579(7798): 270−273. doi:  10.1038/s41586-020-2012-7
    [46] Zhu N, Zhang DY, Wang WL, Li XW, Yang B, Song JD, et al. 2020. A novel coronavirus from patients with pneumonia in China, 2019. The New England Journal of Medicine, 382(8): 727−733. doi:  10.1056/NEJMoa2001017
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出版历程
  • 收稿日期:  2020-07-15
  • 网络出版日期:  2020-07-21
  • 刊出日期:  2020-09-18

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