For best viewing of the website please use Mozilla Firefox or Google Chrome.
Citation: Bali Zhao, Maohua Zhong, Qingyu Yang, Ke Hong, Jianbo Xia, Xia Li, Ying Liu, Yao-Qing Chen, Jingyi Yang, Chaolin Huang, Huimin Yan. Alterations in Phenotypes and Responses of T Cells Within 6 Months of Recovery from COVID-19: A Cohort Study [J].VIROLOGICA SINICA.  http://dx.doi.org/10.1007/s12250-021-00348-0

Alterations in Phenotypes and Responses of T Cells Within 6 Months of Recovery from COVID-19: A Cohort Study

  • The COVID-19 pandemic, caused by the SARS-CoV-2 infection, is a global health crisis. While many patients have clinically recovered, little is known about long-term alterations in T cell responses of COVID-19 convalescents. In this study, T cell responses in peripheral blood mononuclear cells of a long-time COVID-19 clinically recovered (20–26 weeks) cohort (LCR) were measured via flow cytometry and ELISpot. The T cell responses of LCR were comparatively analyzed against an age and sex matched short-time clinically recovered (4–9 weeks) cohort (SCR) and a healthy donor cohort (HD). All volunteers were recruited from Wuhan Jinyintan Hospital, China. Phenotypic analysis showed that activation marker PD-1 expressing on CD4+ T cells of LCR was still significantly lower than that of HD. Functional analysis indicated that frequencies of Tc2, Th2 and Th17 in LCR were comparable to those of HD, but Tc17 was higher than that of HD. In LCR, compared to the HD, there were fewer IFN-γ producing T cells but more IL-2 secreting T cells. In addition, the circulating Tfh cells in LCR were still slightly lower compared to HD, though the subsets composition had recovered. Remarkably, SARS-CoV-2 specific T cell responses in LCR were comparable to that of SCR. Collectively, T cell responses experienced long-term alterations in phenotype and functional potential of LCR cohort. However, after clinical recovery, SARS-CoV-2 specific T cell responses could be sustained at least for six months, which may be helpful in resisting re-infection.

  • 加载中
  • s12250-021-00348-0-ESM.pdf
    1. Ahmed F, Ibrahim A, Cooper CL, Kumar A, Crawley AM (2019) Chronic hepatitis C virus infection impairs M1 macrophage differentiation and contributes to CD8(+) T-cell dysfunction. Cells 8:374

    2. Callaway E (2020) Coronavirus vaccines: five key questions as trials begin. Nature 579:481

    3. Canete PF, Vinuesa CG (2020) COVID-19 makes B cells forget, but T cells remember. Cell 183:13–15

    4. Cao B, Wang Y, Wen D, Liu W, Wang J, Fan G, Ruan L, Song B, Cai Y, Wei M, Li X, Xia J, Chen N, Xiang J, Yu T, Bai T, Xie X, Zhang L, Li C, Yuan Y, Chen H, Li H, Huang H, Tu S, Gong F, Liu Y, Wei Y, Dong C, Zhou F, Gu X, Xu J, Liu Z, Zhang Y, Shang L, Wang K, Li K, Zhou X, Dong X, Qu Z, Lu S, Hu X, Ruan S, Luo S, Wu J, Peng L, Cheng F, Pan L, Zou J, Jia C, Liu X, Wang S, Wu X, Ge Q, He J, Zhan H, Qiu F, Guo L, Huang C, Jaki T, Hayden FG, Horby PW, Zhang D, Wang C (2020) A trial of Lopinavir-Ritonavir in adults hospitalized with severe covid-19. N Engl J Med. https://doi.org/10.1056/NEJMoa2001282

    5. Corey L, Mascola JR, Fauci AS, Collins FS (2020) A strategic approach to COVID-19 vaccine R&D. Science 368:948–950

    6. Cox RJ, Brokstad KA (2020) Not just antibodies: B cells and T cells mediate immunity to COVID-19. Nat Rev Immunol. https://doi.org/10.1038/s41577-020-00436-4

    7. Crotty S (2019) T follicular helper cell biology: a decade of discovery and diseases. Immunity 50:1132–1148

    8. Douek DC, Brenchley JM, Betts MR, Ambrozak DR, Hill BJ, Okamoto Y, Casazza JP, Kuruppu J, Kunstman K, Wolinsky S, Grossman Z, Dybul M, Oxenius A, Price DA, Connors M, Koup RA (2002) HIV preferentially infects HIV-specific CD4+ T cells. Nature 417:95–98

    9. Grifoni A, Weiskopf D, Ramirez SI, Mateus J, Dan JM, Moderbacher CR, Rawlings SA, Sutherland A, Premkumar L, Jadi RS, Marrama D, de Silva AM, Frazier A, Carlin AF, Greenbaum JA, Peters B, Krammer F, Smith DM, Crotty S, Sette A (2020) Targets of T cell responses to SARS-CoV-2 coronavirus in humans with COVID-19 disease and unexposed individuals. Cell 181:1489–1501.e1415

    10. Kaneko N, Kuo HH, Boucau J, Farmer JR, Allard-Chamard H, Mahajan VS, Piechocka-Trocha A, Lefteri K, Osborn M, Bals J, Bartsch YC, Bonheur N, Caradonna TM, Chevalier J, Chowdhury F, Diefenbach TJ, Einkauf K, Fallon J, Feldman J, Finn KK, Garcia-Broncano P, Hartana CA, Hauser BM, Jiang C, Kaplonek P, Karpell M, Koscher EC, Lian X, Liu H, Liu J, Ly NL, Michell AR, Rassadkina Y, Seiger K, Sessa L, Shin S, Singh N, Sun W, Sun X, Ticheli HJ, Waring MT, Zhu AL, Alter G, Li JZ, Lingwood D, Schmidt AG, Lichterfeld M, Walker BD, Yu XG, Padera RF Jr, Pillai S, Massachusetts Consortium on Pathogen Readiness Specimen Working G (2020) Loss of Bcl-6-expressing T follicular helper cells and germinal centers in COVID-19. Cell 183:143–157.e113

    11. Kissler SM, Tedijanto C, Goldstein E, Grad YH, Lipsitch M (2020) Projecting the transmission dynamics of SARS-CoV-2 through the postpandemic period. Science 368:860–868

    12. Leslie M (2020) T cells found in coronavirus patients “bode well” for long-term immunity. Science 368:809–810

    13. Liu WJ, Zhao M, Liu K, Xu K, Wong G, Tan W, Gao GF (2017) T-cell immunity of SARS-CoV: implications for vaccine development against MERS-CoV. Antiviral Res 137:82–92

    14. Long D, Chen Y, Wu H, Zhao M, Lu Q (2019) Clinical significance and immunobiology of IL-21 in autoimmunity. J Autoimmun 99:1–14

    15. Long QX, Tang XJ, Shi QL, Li Q, Deng HJ, Yuan J, Hu JL, Xu W, Zhang Y, Lv FJ, Su K, Zhang F, Gong J, Wu B, Liu XM, Li JJ, Qiu JF, Chen J, Huang AL (2020) Clinical and immunological assessment of asymptomatic SARS-CoV-2 infections. Nat Med 26:1200–1204

    16. Lucas C, Wong P, Klein J, Castro TBR, Silva J, Sundaram M, Ellingson MK, Mao T, Oh JE, Israelow B, Takahashi T, Tokuyama M, Lu P, Venkataraman A, Park A, Mohanty S, Wang H, Wyllie AL, Vogels CBF, Earnest R, Lapidus S, Ott IM, Moore AJ, Muenker MC, Fournier JB, Campbell M, Odio CD, Casanovas-Massana A, Yale IT, Herbst R, Shaw AC, Medzhitov R, Schulz WL, Grubaugh ND, Dela Cruz C, Farhadian S, Ko AI, Omer SB, Iwasaki A (2020) Longitudinal analyses reveal immunological misfiring in severe COVID-19. Nature 584:463–469

    17. Mathew D, Giles JR, Baxter AE, Oldridge DA, Greenplate AR, Wu JE, Alanio C, Kuri-Cervantes L, Pampena MB, D’Andrea K, Manne S, Chen Z, Huang YJ, Reilly JP, Weisman AR, Ittner CAG, Kuthuru O, Dougherty J, Nzingha K, Han N, Kim J, Pattekar A, Goodwin EC, Anderson EM, Weirick ME, Gouma S, Arevalo CP, Bolton MJ, Chen F, Lacey SF, Ramage H, Cherry S, Hensley SE, Apostolidis SA, Huang AC, Vella LA, Unit UPCP, Betts MR, Meyer NJ, Wherry EJ (2020) Deep immune profiling of COVID-19 patients reveals distinct immunotypes with therapeutic implications. Science 369:15

    18. Morita R, Schmitt N, Bentebibel SE, Ranganathan R, Bourdery L, Zurawski G, Foucat E, Dullaers M, Oh S, Sabzghabaei N, Lavecchio EM, Punaro M, Pascual V, Banchereau J, Ueno H (2011) Human blood CXCR5(+)CD4(+) T cells are counterparts of T follicular cells and contain specific subsets that differentially support antibody secretion. Immunity 34:108–121

    19. Ni L, Ye F, Cheng ML, Feng Y, Deng YQ, Zhao H, Wei P, Ge J, Gou M, Li X, Sun L, Cao T, Wang P, Zhou C, Zhang R, Liang P, Guo H, Wang X, Qin CF, Chen F, Dong C (2020) Detection of SARS-CoV-2-specific humoral and cellular immunity in COVID-19 convalescent individuals. Immunity 52:971–977.e973

    20. Peng Y, Mentzer AJ, Liu G, Yao X, Yin Z, Dong D, Dejnirattisai W, Rostron T, Supasa P, Liu C, Lopez-Camacho C, Slon-Campos J, Zhao Y, Stuart DI, Paesen GC, Grimes JM, Antson AA, Bayfield OW, Hawkins D, Ker DS, Wang B, Turtle L, Subramaniam K, Thomson P, Zhang P, Dold C, Ratcliff J, Simmonds P, de Silva T, Sopp P, Wellington D, Rajapaksa U, Chen YL, Salio M, Napolitani G, Paes W, Borrow P, Kessler BM, Fry JW, Schwabe NF, Semple MG, Baillie JK, Moore SC, Openshaw PJM, Ansari MA, Dunachie S, Barnes E, Frater J, Kerr G, Goulder P, Lockett T, Levin R, Zhang Y, Jing R, Ho LP, Oxford Immunology Network Covid-19 Response TcC, Investigators IC, Cornall RJ, Conlon CP, Klenerman P, Screaton GR, Mongkolsapaya J, McMichael A, Knight JC, Ogg G, Dong T (2020) Broad and strong memory CD4(+) and CD8(+) T cells induced by SARS-CoV-2 in UK convalescent individuals following COVID-19. Nat Immunol. https://doi.org/10.1038/s41590-020-0782-6

    21. Qin C, Zhou L, Hu Z, Zhang S, Yang S, Tao Y, Xie C, Ma K, Shang K, Wang W, Tian DS (2020) Dysregulation of Immune Response in Patients With Coronavirus 2019 (COVID-19) in Wuhan, China. Clin Infect Dis 71:762–768

    22. Rydyznski Moderbacher C, Ramirez SI, Dan JM, Grifoni A, Hastie KM, Weiskopf D, Belanger S, Abbott RK, Kim C, Choi J, Kato Y, Crotty EG, Kim C, Rawlings SA, Mateus J, Tse LPV, Frazier A, Baric R, Peters B, Greenbaum J, Ollmann Saphire E, Smith DM, Sette A, Crotty S (2020) Antigen-specific adaptive immunity to SARS-CoV-2 in acute COVID-19 s. Cell. https://doi.org/10.1016/j.cell.2020.09.038

    23. Sekine T, Perez-Potti A, Rivera-Ballesteros O, Stralin K, Gorin JB, Olsson A, Llewellyn-Lacey S, Kamal H, Bogdanovic G, Muschiol S, Wullimann DJ, Kammann T, Emgard J, Parrot T, Folkesson E, Karolinska C-SG, Rooyackers O, Eriksson LI, Henter JI, Sonnerborg A, Allander T, Albert J, Nielsen M, Klingstrom J, Gredmark-Russ S, Bjorkstrom NK, Sandberg JK, Price DA, Ljunggren HG, Aleman S, Buggert M (2020) Robust T cell immunity in convalescent individuals with asymptomatic or mild COVID-19. Cell 183:158–168.e114

    24. Thevarajan I, Nguyen THO, Koutsakos M, Druce J, Caly L, van de Sandt CE, Jia X, Nicholson S, Catton M, Cowie B, Tong SYC, Lewin SR, Kedzierska K (2020) Breadth of concomitant immune responses prior to patient recovery: a case report of non-severe COVID-19. Nat Med 26:453–455

    25. Yang W, Bai Y, Xiong Y, Zhang J, Chen S, Zheng X, Meng X, Li L, Wang J, Xu C, Yan C, Wang L, Chang CC, Chang TY, Zhang T, Zhou P, Song BL, Liu W, Sun SC, Liu X, Li BL, Xu C (2016) Potentiating the antitumour response of CD8(+) T cells by modulating cholesterol metabolism. Nature 531:651–655

    26. Yang J, Zhang E, Zhong M, Yang Q, Hong K, Shu T, Zhou D, Xiang J, Xia J, Zhou X, Zhang D, Huang C, Shang Y, Yan H (2020a) Longitudinal characteristics of T cell responses in asymptomatic SARS-CoV-2 infection. Virol Sin. https://doi.org/10.1007/s12250-020-00277-4

    27. Yang J, Zhong M, Zhang E, Hong K, Yang Q, Zhou D, Xia J, Chen Y, Sun M, Zhao B, Xiang J, Liu Y, Han Y, Zhou X, Huang C, Y. S, Yan H (2020b) Broad phenotypic alterations and potential dysfunctions of lymphocytes in COVID-19 recovered individuals. Preprint at medRxiv

    28. Zhang X, Tan Y, Ling Y, Lu G, Liu F, Yi Z, Jia X, Wu M, Shi B, Xu S, Chen J, Wang W, Chen B, Jiang L, Yu S, Lu J, Wang J, Xu M, Yuan Z, Zhang Q, Zhang X, Zhao G, Wang S, Chen S, Lu H (2020) Viral and host factors related to the clinical outcome of COVID-19. Nature 583:437–440

    29. Zhou T, Su TT, Mudianto T, Wang J (2020) Immune asynchrony in COVID-19 pathogenesis and potential immunotherapies. J Exp Med 217:e20200674

    30. Zhu L, Yang P, Zhao Y, Zhuang Z, Wang Z, Song R, Zhang J, Liu C, Gao Q, Xu Q, Wei X, Sun HX, Ye B, Wu Y, Zhang N, Lei G, Yu L, Yan J, Diao G, Meng F, Bai C, Mao P, Yu Y, Wang M, Yuan Y, Deng Q, Li Z, Huang Y, Hu G, Liu Y, Wang X, Xu Z, Liu P, Bi Y, Shi Y, Zhang S, Chen Z, Wang J, Xu X, Wu G, Wang FS, Gao GF, Liu L, Liu WJ (2020) Single-cell sequencing of peripheral mononuclear cells reveals distinct immune response landscapes of COVID-19 and influenza patients. Immunity 53:685–696.e683

  • 加载中

Article Metrics

Article views(2200) PDF downloads(2) Cited by()

Related
Proportional views
    通讯作者: 陈斌, bchen63@163.com
    • 1. 

      沈阳化工大学材料科学与工程学院 沈阳 110142

    1. 本站搜索
    2. 百度学术搜索
    3. 万方数据库搜索
    4. CNKI搜索

    Alterations in Phenotypes and Responses of T Cells Within 6 Months of Recovery from COVID-19: A Cohort Study

      Corresponding author: Yao-Qing Chen, chenyaoqing@mail.sysu.edu.cn
      Corresponding author: Jingyi Yang, jyyang875@163.com
      Corresponding author: Chaolin Huang, chaolin2020@163.com
      Corresponding author: Huimin Yan, hmyan@wh.iov.cn
    • 1 State Key Laboratory of Virology, Wuhan Institute of Virology, Center for Biosafety Mega-Science, CAS, Wuhan 430071, China;
    • 2 Institute of Infection, Immunology and Tumor Microenvironment, Hubei Province Key Laboratory of Occupational Hazard Identification and Control, Medical College, Wuhan University of Science and Technology, Wuhan 430065, China;
    • 3 School of Public Health(Shenzhen), Sun Yat-Sen University, Shenzhen 518107, China;
    • 4 Shanghai Public Health Clinical Center, Fudan University, Shanghai 201508, China;
    • 5 Joint Laboratory of Infectious Diseases and Health, Wuhan Institute of Virology & Wuhan Jinyintan Hospital, Wuhan Jinyintan Hospital, Wuhan 430023, China;
    • 6 Center for Translational Medicine, Jinyintan Hospital, Wuhan 430023, China;
    • 7 Department of Laboratory Medicine, Maternal and Child Health Hospital of Hubei Province, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430070, China;
    • 8 The Office of Drug Clinical Trial Institution, Jinyintan Hospital, Wuhan 430023, China;
    • 9 University of Chinese Academy of Sciences, Beijing 100049, China

    Abstract: The COVID-19 pandemic, caused by the SARS-CoV-2 infection, is a global health crisis. While many patients have clinically recovered, little is known about long-term alterations in T cell responses of COVID-19 convalescents. In this study, T cell responses in peripheral blood mononuclear cells of a long-time COVID-19 clinically recovered (20–26 weeks) cohort (LCR) were measured via flow cytometry and ELISpot. The T cell responses of LCR were comparatively analyzed against an age and sex matched short-time clinically recovered (4–9 weeks) cohort (SCR) and a healthy donor cohort (HD). All volunteers were recruited from Wuhan Jinyintan Hospital, China. Phenotypic analysis showed that activation marker PD-1 expressing on CD4+ T cells of LCR was still significantly lower than that of HD. Functional analysis indicated that frequencies of Tc2, Th2 and Th17 in LCR were comparable to those of HD, but Tc17 was higher than that of HD. In LCR, compared to the HD, there were fewer IFN-γ producing T cells but more IL-2 secreting T cells. In addition, the circulating Tfh cells in LCR were still slightly lower compared to HD, though the subsets composition had recovered. Remarkably, SARS-CoV-2 specific T cell responses in LCR were comparable to that of SCR. Collectively, T cell responses experienced long-term alterations in phenotype and functional potential of LCR cohort. However, after clinical recovery, SARS-CoV-2 specific T cell responses could be sustained at least for six months, which may be helpful in resisting re-infection.

    Reference (30) Relative (20)

    目录

    /

    DownLoad:  Full-Size Img  PowerPoint
    Return
    Return