Manuscript title: Loss in the expansion of SARS-CoV-2 specific immunity is a key risk factor in fatal patients with COVID-19

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Abstract

Knowledge of the dynamic immunological characteristics of patients with coronavirus disease 2019 (COVID-19) is essential for clinicians to understand the progression of the disease. Our data showed that the immune system and function gradually remodeled and declined with age, starting from age 16 until age 91 in 25,239 healthy controls. An analysis of the relationship between the number of lymphocytes and age revealed that the lymphocyte and subset counts tended to decline with age significantly. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-specific immunity declined with age and was associated with survival time in fatal cases. Loss in the expansion of SARS-CoV-2-specific immunity could be expanded in vitro . The concurrent decline in SARS-CoV-2-specific cellular and humoral immunities and prolonged SARS-CoV-2 exposure predicted fatal outcomes. Our findings provide a basis for further analysis of SARS-CoV-2-specific immunity and understanding of the pathogenesis of fatal COVID-19 cases.

    Highlights

  • The immune system and function gradually remodeled and declined with age .

  • SARS-CoV-2-specific immunity declined with age in fatal cases .

  • SARS-CoV-2-specific immunity was associated with survival time in fatal cases .

  • Loss in the expansion of SARS-CoV-2-specific immunity could be expanded in vitro .

  • A concurrent decline in SARS-CoV-2-specific cellular and humoral immunities and prolonged SARS-CoV-2 exposure predicted fatal outcomes .

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  1. SciScore for 10.1101/2020.07.29.20164681: (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.

    Table 2: Resources

    Antibodies
    SentencesResources
    The cells were then stained with anti-IFNγ antibodies (BD Bioscience, USA) for 30 min at 4 °C.
    anti-IFNγ
    suggested: None
    Enzyme-linked immunosorbent assay (ELISA) of immunoglobulin (Ig): Antibodies (IgM, IgA, and IgG) specific to SARS-CoV-2 were determined with two different ELISA: an in-house assay using SARS-CoV-2 Receptor Binding Domain (RBD) protein (Cat. #Z03479, Genscript Biotech, USA) as an antigen, or a commercial kit (SARS-CoV-2
    IgM , IgA
    suggested: None
    IgG
    suggested: None
    SARS-CoV-2 Receptor Binding Domain ( RBD
    suggested: None
    a commercial kit
    suggested: None
    Software and Algorithms
    SentencesResources
    The data were analyzed by FlowJo software (version 10, Tree Star, USA)
    FlowJo
    suggested: (FlowJo, RRID:SCR_008520)
    All statistical analyses were performed using SPSS (Statistical Package for the Social Sciences Inc., version 13.0).
    SPSS
    suggested: (SPSS, RRID:SCR_002865)
    Statistical Package for the Social Sciences
    suggested: (SPSS, RRID:SCR_002865)

    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.
    • Thank you for including a funding statement. Authors are encouraged to include this statement when submitting to a journal.
    • 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.