Impaired Cellular Immunity to SARS-CoV-2 in Severe COVID-19 Patients

  1. Ling Ni
  2. Meng-Li Cheng
  3. Yu Feng
  4. Hui Zhao
  5. Jingyuan Liu
  6. Fang Ye
  7. Qing Ye
  8. Gengzhen Zhu
  9. Xiaoli Li
  10. Pengzhi Wang
  11. Jing Shao
  12. Yong-Qiang Deng
  13. Peng Wei
  14. Fang Chen
  15. Cheng-Feng Qin
  16. Guoqing Wang
  17. Fan Li
  18. Hui Zeng
  19. Chen Dong

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Abstract

The high infection rate and rapid spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) make it a world-wide pandemic. Individuals infected by the virus exhibited different degrees of symptoms, and most convalescent individuals have been shown to develop both cellular and humoral immune responses. However, virus-specific adaptive immune responses in severe patients during acute phase have not been thoroughly studied. Here, we found that in a group of COVID-19 patients with acute respiratory distress syndrome (ARDS) during hospitalization, most of them mounted SARS-CoV-2-specific antibody responses, including neutralizing antibodies. However, compared to healthy controls, the percentages and absolute numbers of both NK cells and CD8 + T cells were significantly reduced, with decreased IFNγ expression in CD4 + T cells in peripheral blood from severe patients. Most notably, their peripheral blood lymphocytes failed in producing IFNγ against viral proteins. Thus, severe COVID-19 patients at acute infection stage developed SARS-CoV-2-specific antibody responses but were impaired in cellular immunity, which emphasizes on the role of cellular immunity in COVID-19.

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  1. Version published to 10.3389/fimmu.2021.603563
  2. ScreenIT

    SciScore for 10.1101/2020.08.10.20171371: (What is this?)

    Please note, not all rigor criteria are appropriate for all manuscripts.

    Table 1: Rigor

    Institutional Review Board Statementnot detected.
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot detected.
    Sex as a biological variablenot detected.
    Cell Line Authenticationnot detected.

    Table 2: Resources

    Antibodies
    SentencesResources
    An anti-Human IgG-biotin conjugated monoclonal antibody (Cat. SSA009, Sino Biological Inc., Wayne, PA) and streptavidin-HRP were used at a dilution of 1: 5000 and 1:250, respectively, and anti-human IgM-HRP conjugated monoclonal antibody (Cat. bs-0345G-HRP,
    anti-Human IgG-biotin
    suggested: None
    anti-human IgM-HRP
    suggested: (SouthernBiotech Cat# 2020-05, RRID:AB_2795603)
    In order to quantify the amount of anti-NP/S-RBD IgG or anti-NP/S-RBD IgM present in each specimen, the positive control standard was run on each plate to calculate antibody titers (relative units) for all samples using non-linear regression interpolations.
    anti-NP/S-RBD IgG
    suggested: None
    anti-NP/S-RBD IgM
    suggested: None
    After washing, an anti-Human IgG1-HRP conjugated monoclonal antibody (Cat. C030248, BaiaoTong Experiment Center, LY), and an anti-human IgG3-HRP conjugated monoclonal antibody (Cat.C030246, BaiaoTong Experiment Center, LY), all validated by the company for their specificity, were used at a dilution of 1:4000 for 1 h at RT.
    anti-Human IgG1-HRP
    suggested: None
    anti-human IgG3-HRP
    suggested: None
    Experimental Models: Cell Lines
    SentencesResources
    The recombinant His-tagged S-RBD (amino acids 319-541) was expressed by a mammalian system in 293F cells.
    293F
    suggested: RRID:CVCL_D615)
    pNL43Luci and GP-pCAGGS were co-transfected into 293T cells.
    293T
    suggested: NCBI_Iran Cat# C498, RRID:CVCL_0063)
    Then the mixtures were transferred to 96-well plates containing monolayers of Huh-7 cells (Nie et al., 2020).
    Huh-7
    suggested: None
    Software and Algorithms
    SentencesResources
    The area under the curve (AUC) was calculated by Prism 8 (Graphpad)
    Graphpad
    suggested: (GraphPad, RRID:SCR_000306)
    The neutralizing antibody titer (NAT50) were calculated by performing S-fit analysis via Graphpad Prism 7 software.
    Graphpad Prism
    suggested: (GraphPad Prism, RRID:SCR_002798)
    FACS staining: PBMCs were washed with PBS plus 2% FBS (Gibco, Grand Island, NY), and then Fc blocking reagent (Meltenyi Biotec, Inc., Auburn, CA) was added followed by a wash with PBS plus 2% FBS.
    Meltenyi Biotec
    suggested: None
    Data were analyzed using FlowJo software (Version 10.0.8
    FlowJo
    suggested: (FlowJo, RRID:SCR_008520)

    Results from OddPub: We did not detect open data. We also did not detect open code. Researchers are encouraged to share open data when possible (see Nature blog).

    Results from LimitationRecognizer: An explicit section about the limitations of the techniques employed in this study was not found. We encourage authors to address study limitations.

    Results from TrialIdentifier: No clinical trial numbers were referenced.

    Results from Barzooka: We did not find any issues relating to the usage of bar graphs.

    Results from JetFighter: We did not find any issues relating to colormaps.

    Results from rtransparent:
    • Thank you for including a conflict of interest statement. Authors are encouraged to include this statement when submitting to a journal.
    • No funding statement was detected.
    • No protocol registration statement was detected.

    About SciScore

    SciScore is an automated tool that is designed to assist expert reviewers by finding and presenting formulaic information scattered throughout a paper in a standard, easy to digest format. SciScore checks for the presence and correctness of RRIDs (research resource identifiers), and for rigor criteria such as sex and investigator blinding. For details on the theoretical underpinning of rigor criteria and the tools shown here, including references cited, please follow this link.

  3. Version published to 10.1101/2020.08.10.20171371v1 on medRxiv