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Citation: Ran Jia,  Xiangshi Wang,  Pengcheng Liu,  Xiaozhen Liang,  Yanling Ge,  He Tian,  Hailing Chang,  Hao Zhou,  Mei Zeng,  Jin Xu. Mild Cytokine Elevation, Moderate CD4+ T Cell Response and Abundant Antibody Production in Children with COVID-19 [J].VIROLOGICA SINICA.  http://dx.doi.org/10.1007/s12250-020-00265-8

Mild Cytokine Elevation, Moderate CD4+ T Cell Response and Abundant Antibody Production in Children with COVID-19

  • Corresponding author: Jin Xu, jinxu_125@163.com
  • Received Date: 02 July 2020
    Accepted Date: 06 July 2020
    Published Date: 22 July 2020
  • Children with Coronavirus Disease 2019 (COVID-19) were reported to show milder symptoms and better prognosis than their adult counterparts, but the difference of immune response against SARS-CoV-2 between children and adults hasn’t been reported. Therefore we initiated this study to figure out the features of immune response in children with COVID-19. Sera and whole blood cells from 19 children with COVID-19 during different phases after disease onset were collected. The cytokine concentrations, SARS-CoV-2 S-RBD or N-specific antibodies and T cell immune responses were detected respectively. In children with COVID-19, only 3 of 12 cytokines were increased in acute sera, including interferon (IFN)-γ-induced protein 10 (IP10), interleukin (IL)-10 and IL-16. We observed an increase in T helper (Th)-2 cells and a suppression in regulatory T cells (Treg) in patients during acute phase, but no significant response was found in the IFN-γ-producing or tumor necrosis factor (TNF)-α-producing CD8+ T cells in patients. S-RBD and N IgM showed an early induction, while S-RBD and N IgG were prominently induced later in convalescent phase. Potent S-RBD IgA response was observed but N IgA seemed to be inconspicuous. Children with COVID-19 displayed an immunophenotype that is less inflammatory than adults, including unremarkable cytokine elevation, moderate CD4+ T cell response and inactive CD8+ T cell response, but their humoral immunity against SARS-CoV-2 were as strong as adults. Our finding presented immunological characteristics of children with COVID-19 and might give some clues as to why children develop less severe disease than adults.

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    1. Azkur AK, Akdis M, Azkur D, Sokolowska M, van de Veen W, Brüggen MC, O’Mahony L, Gao Y, Nadeau K, Akdis CA (2020) Immune response to SARS-CoV-2 and mechanisms of immunopathological changes in COVID-19. Allergy. https://doi.org/10.1111/all.14364

    2. Chen G, Wu D, Guo W, Cao Y, Huang D, Wang HW, Wang T, Zhang XY, Chen HL, Yu HJ, Zhang XP, Zhang MX, Wu SJ, Song JX, Chen T, Han MF, Li SS, Luo XP, Zhao JP, Ning Q (2020)

    3. Clinical and immunologic features in severe and moderate Coronavirus disease 2019. J Clin Invest. https://doi.org/10.1172/JCI137244

    4. Guo B, Rothstein TL (2013) IL-4 upregulates Iga and Igb protein, resulting in augmented IgM maturation and B cell receptortriggered B cell activation. J Immunol 191:670–677

    5. Huang C, Wang Y, Li X, Ren L, Zhao J, Hu Y, Zhang L, Fan G, Xu J, Gu X, Cheng Z, Yu T, Xia J, Wei Y, Wu W, Xie X, Yin W, Li H, Liu M, Xiao Y, Gao H, Guo L, Xie J, Wang G, Jiang R, Gao Z, Jin Q, Wang J, Cao B (2020) Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. Lancet 395:497–506

    6. Ichikawa A, Kuba K, Morita M, Chida S, Tezuka H, Hara H, Sasaki T, Ohteki T, Ranieri VM, dos Santos CC, Kawaoka Y, Akira S, Luster AD, Lu B, Penninger JM, Uhlig S, Slutsky AS, Imai Y (2013) CXCL10-CXCR3 enhances the development of neutrophil-mediated fulminant lung injury of viral and nonviral origin. Am J Respir Crit Care Med 187:6–77

    7. Jia R, Liu S, Xu J, Liang X (2020) IL16 deficiency enhances Th1 and cytotoxic T lymphocyte response against influenza a virus infection. Biosci Trends 13:516–522

    8. León B, Ballesteros-Tato A, Lund FE (2014) Dendritic cells and B cells: unexpected partners in Th2 development. J Immunol 193:1531–1537

    9. Li CK, Wu H, Yan H, Ma S, Wang L, Zhang M, Tang X, Temperton NJ, Weiss RA, Brenchley JM, Douek DC, Mongkolsapaya J, Tran BH, Lin CL, Screaton GR, Hou JL, McMichael AJ, Xu XN (2008) T cell responses to whole SARS coronavirus in humans. J Immunol 181:5490–5500

    10. Li C, Dai J, Dong G, Ma Q, Li Z, Zhang H, Yan F, Zhang J, Wang B, Shi H, Zhu Y, Yao X, Si C, Xiong H (2019) Interleukin-16 aggravates ovalbumin-induced allergic inflammation by enhancing Th2 and Th17 cytokine production in a mouse model. Immunology 157:257–267

    11. Liu P, Cai J, Jia R, Xia S, Wang X, Cao L, Zeng M, Xu J (2020) Dynamic surveillance of SARS-CoV-2 shedding and neutralizing antibody in children with COVID-19. Emerg Microbes Infect 9:1254–1258

    12. Ludvigsson JF (2020) Systematic review of COVID-19 in children shows milder cases and a better prognosis than adults. Acta Paediatr. https://doi.org/10.1111/apa.15270

    13. Lycke N (1998) T cell and cytokine regulation of the IgA response. Chem Immunol 71:209–234

    14. Marconi M, Plebani A, Avanzini MA, Maccario R, Pistorio A, Duse M, Stringa M, Monafo V (1998) IL-10 and IL-4 co-operate to normalize in vitro IgA production in IgA-deficient (IgAD) patients. Clin Exp Immunol 112:528–532

    15. Matricardi PM, Dal Negro RW, Nisini R (2020) The first, holistic immunological model of COVID-19: implications for prevention, diagnosis, and public health measures. Pediatr Allergy Immunol. https://doi.org/10.1111/pai.13271

    16. Mehta P, McAuley DF, Brown M, Sanchez E, Tattersall RS, Manson JJ (2020) COVID-19: consider cytokine storm syndromes and immunosuppression. Lancet 395:1033–1034

    17. Okba NMA, Müller MA, Li W, Wang C, GeurtsvanKessel CH, Corman VM, Lamers MM, Sikkema RS, de Bruin E, Chandler FD, Yazdanpanah Y, Le Hingrat Q, Descamps D, HouhouFidouh N, Reusken CBEM, Bosch BJ, Drosten C, Koopmans MPG, Haagmans BL (2020) Severe acute respiratory syndrome coronavirus 2-specific antibody responses in coronavirus disease 2019 patients. Emerg Infect Dis. https://doi.org/10.3201/eid2607.200841

    18. Pedersen SF, HO YC (2020) SARS-CoV-2: a storm is raging. J Clin Invest. https://doi.org/10.1172/JCI137647

    19. Qin C, Zhou LQ, Hu ZW, Zhang SQ, Yang S, Tao Y, Xie CH, Ma K, Shang K, Wang W, Tian DS (2020) Dysregulation of immune response in patients with COVID-19 in Wuhan. China. Clin Infect Dis. https://doi.org/10.1093/cid/ciaa248

    20. Sampson DL, Fox BA, Yager TD, Bhide S, Cermelli S, McHugh LC, Seldon TA, Brandon RA, Sullivan E, Zimmerman JJ, Noursadeghi M, Brandon RB (2017) A four-biomarker blood signature discriminates systemic inflammation due to viral infection versus other etiologies. Sci Rep 7:2914

    21. Saxena A, Khosraviani S, Noel S, Mohan D, Donner T, Hamad AR (2015) Interleukin-10 paradox: a potent immunoregulatory cytokine that has been difficult to harness for immunotherapy. Cytokine 74:27–34

    22. Su L, Ma X, Yu H, Zhang ZH, Bian PF, Han YL, Jing S, Liu YQ, Yang C, Geng J, Zhang ZF, Gai ZT (2020) The different clinical characteristics of corona virus disease cases between children and their families in China—the character of children with COVID-19. Emerg Microbes Infect 9:707–713

    23. Velavan TP, Meyer CG (2020) The COVID-19 epidemic. Trop Med Int Health 25:278–280

    24. Wang F, Hou HY, Luo Y, Tang GX, Wu SJ, Huang M, Liu WY, Zhu YW, Lin Q, Mao LY, Fang MH, Zhang HL, Sun ZY (2020) The laboratory tests and host immunity of COVID-19 patients with different severity of illness. JCI Insight. https://doi.org/10.1172/jci.insight.137799

    25. Yamamoto M, Vancott JL, Okahashi N, Marinaro M, Kiyono H, Fujihashi K, Jackson RJ, Chatfield SN, Bluethmann H, McGhee JR (1996) The role of Th1 and Th2 cells for mucosal IgA responses. Ann N Y Acad Sci 778:64–71

    26. Yang Y, Shen C, Li J, Yuan J, Wei J, Huang F, Wang F, Li G, Li Y, Xing L, Peng L, Yang M, Cao M, Zheng H, Wu W, Zou R, Li D, Xu Z, Wang H, Zhang M, Zhang Z, Gao GF, Jiang C, Liu L, Liu Y (2020) Plasma IP-10 and MCP-3 levels are highly associated with disease severity and predict the progression of COVID-19.J Allergy Clin Immunol. https://doi.org/10.1016/j.jaci.2020.04.027

    27. Zhang J, Yu M, Tong S, Liu LY, Tang LV (2020) Predictive factors for disease progression in hospitalized patients with coronavirus disease 2019 in Wuhan, China. J Clin Virol 127:104392

    28. Zhao J, Yuan Q, Wang H, Liu W, Liao X, Su Y, Wang X, Yuan J, Li T, Li J, Qian S, Hong C, Wang F, Liu Y, Wang Z, He Q, Li Z, He B, Zhang T, Fu Y, Ge S, Liu L, Zhang J, Xia N, Zhang Z (2020) Antibody responses to SARS-CoV-2 in patients of novel coronavirus disease 2019. Clin Infect Dis. https://doi.org/10. 1093/cid/ciaa344

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    Mild Cytokine Elevation, Moderate CD4+ T Cell Response and Abundant Antibody Production in Children with COVID-19

      Corresponding author: Jin Xu, jinxu_125@163.com
    • 1 Department of Clinical Laboratory, Children’s Hospital of Fudan University, Shanghai 201102, China
    • 2 Department of Infectious Diseases, Children’s Hospital of Fudan University, Shanghai 201102, China
    • 3 Key Laboratory of Molecular Virology & Immunology, Institut Pasteur of Shanghai, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai 200031, China
    • 4 Shanghai Kehua Bio-Engineering Co., Ltd., Shanghai 200233, China

    Abstract: Children with Coronavirus Disease 2019 (COVID-19) were reported to show milder symptoms and better prognosis than their adult counterparts, but the difference of immune response against SARS-CoV-2 between children and adults hasn’t been reported. Therefore we initiated this study to figure out the features of immune response in children with COVID-19. Sera and whole blood cells from 19 children with COVID-19 during different phases after disease onset were collected. The cytokine concentrations, SARS-CoV-2 S-RBD or N-specific antibodies and T cell immune responses were detected respectively. In children with COVID-19, only 3 of 12 cytokines were increased in acute sera, including interferon (IFN)-γ-induced protein 10 (IP10), interleukin (IL)-10 and IL-16. We observed an increase in T helper (Th)-2 cells and a suppression in regulatory T cells (Treg) in patients during acute phase, but no significant response was found in the IFN-γ-producing or tumor necrosis factor (TNF)-α-producing CD8+ T cells in patients. S-RBD and N IgM showed an early induction, while S-RBD and N IgG were prominently induced later in convalescent phase. Potent S-RBD IgA response was observed but N IgA seemed to be inconspicuous. Children with COVID-19 displayed an immunophenotype that is less inflammatory than adults, including unremarkable cytokine elevation, moderate CD4+ T cell response and inactive CD8+ T cell response, but their humoral immunity against SARS-CoV-2 were as strong as adults. Our finding presented immunological characteristics of children with COVID-19 and might give some clues as to why children develop less severe disease than adults.

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