Different Innate and Adaptive Immune Responses to SARS-CoV-2 Infection of Asymptomatic, Mild, and Severe Cases

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Abstract

SARS-CoV-2 is a novel coronavirus, not encountered before by humans. The wide spectrum of clinical expression of SARS-CoV-2 illness suggests that individual immune responses to SARS-CoV-2 play a crucial role in determining the clinical course after first infection. Immunological studies have focused on patients with moderate to severe disease, demonstrating excessive inflammation in tissues and organ damage. In order to understand the basis of the protective immune response in COVID-19, we performed a longitudinal follow-up, flow-cytometric and serological analysis of innate and adaptive immunity in 64 adults with a spectrum of clinical presentations: 28 healthy SARS-CoV-2-negative contacts of COVID-19 cases; 20 asymptomatic SARS-CoV-2-infected cases; eight patients with Mild COVID-19 disease and eight cases of Severe COVID-19 disease. Our data show that high frequency of NK cells and early and transient increase of specific IgA, IgM and, to a lower extent, IgG are associated with asymptomatic SARS-CoV-2 infection. By contrast, monocyte expansion and high and persistent levels of IgA and IgG, produced relatively late in the course of the infection, characterize severe disease. Modest increase of monocytes and different kinetics of antibodies are detected in mild COVID-19. The importance of innate NK cells and the short-lived antibody response of asymptomatic individuals and patients with mild disease suggest that only severe COVID-19 may result in protective memory established by the adaptive immune response.

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  1. SciScore for 10.1101/2020.06.22.20137141: (What is this?)

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

    Table 1: Rigor

    Institutional Review Board StatementIRB: Ethical approval: Ethical approval was obtained from the Medical Research and Ethics Committee at Sapienza, University of Rome and from the Ethics Committee at INMI, Lazzaro Spallanzani.
    Consent: According to the guidelines on Italian observational studies as established by the Italian legislation about the obligatory occupational surveillance and privacy management, HCWs confidentiality was safeguarded and the informed consent was obtained from all the participants.
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot detected.
    Sex as a biological variablenot detected.

    Table 2: Resources

    Antibodies
    SentencesResources
    Peripheral blood mononuclear cells (PBMCs) were then stained with antibodies against CD19, CD24, CD27, CD38, IgM, IgG, IgA and IgD (Supplementary Table S2).
    CD19
    suggested: (Agilent Cat# TC67401, RRID:AB_579635)
    CD24
    suggested: None
    CD27
    suggested: None
    CD38
    suggested: None
    IgM , IgG
    suggested: None
    IgD
    suggested: None
    After washing, plates were incubated for 1h at 37°C with peroxidase-conjugated goat anti-human IgM antibody (Jackons ImmunoResearch Laboratories).
    anti-human IgM
    suggested: None
    Absorbance at 450 nm was measured, and IgM concentrations were calculated by interpolation from the standard curve based on serial dilutions of monoclonal human IgM antibody against SARS-CoV-2 Spike-RBD (Invivogen).
    SARS-CoV-2
    suggested: None
    Spike-RBD
    suggested: None
    Due to the unavailability of a human IgM antibody against SARS-CoV-2 S1 to be used as standard we were unable to quantify the level of anti-S1 IgM.
    anti-S1 IgM
    suggested: None
    Software and Algorithms
    SentencesResources
    Data were analyzed with FlowJo ver.
    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: Please consider improving the rainbow (“jet”) colormap(s) used on pages 43, 45, 46, 47 and 49. At least one figure is not accessible to readers with colorblindness and/or is not true to the data, i.e. not perceptually uniform.


    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

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