TNF-α+ CD4+ T cells dominate the SARS-CoV-2 specific T cell response in COVID-19 outpatients and are associated with durable antibodies

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Abstract

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  1. SciScore for 10.1101/2022.01.25.22269670: (What is this?)

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

    Table 1: Rigor

    EthicsConsent: All participants gave written informed consent.
    IRB: The study protocol used was approved by the Institutional Review Board of Stanford University.
    Sex as a biological variablenot detected.
    RandomizationClinical cohort and samples: The samples used were from 109 participants enrolled in a Phase 2, single-blind, randomized placebo-controlled trial evaluating the efficacy of Peginterferon Lambda-1a in SARS-CoV-2 infected outpatients (Jagannathan et al., 2021).
    Blindingnot detected.
    Power Analysisnot detected.
    Cell Line Authenticationnot detected.

    Table 2: Resources

    Antibodies
    SentencesResources
    This is followed by adding 25 μL of 1:5000 diluted horse radish peroxidase (HRP) conjugated anti-Human IgG secondary antibodies (Southern Biotech) and incubated for 1 hour at RT.
    anti-Human IgG
    suggested: None
    Experimental Models: Cell Lines
    SentencesResources
    Prior to infection, Vero cells were washed twice with 1X PBS and then 50 μL of the incubated pseudo-typed particles and patient plasma mixture was transferred onto the Vero cells, followed by a 24 hour incubation at 37°C and 5% CO2.
    Vero
    suggested: None
    Software and Algorithms
    SentencesResources
    We used Prot_M and Prot_N, consisting of complete sequences of the membrane ‘M’ glycoprotein (GenBank MN908947.3,
    Prot_M
    suggested: None
    All samples were analyzed on an Attune NXT flow cytometer and analyzed with FlowJo X (Tree Star) software.
    FlowJo
    suggested: (FlowJo, RRID:SCR_008520)
    A non-linear curve and the half-maximal neutralization titer (NT50) were generated using GraphPad Prism.
    GraphPad Prism
    suggested: (GraphPad Prism, RRID:SCR_002798)
    Statistical analysis: All statistical analyses were performed using Prism 6.0 (GraphPad)
    Prism
    suggested: (PRISM, RRID:SCR_005375)
    GraphPad
    suggested: (GraphPad Prism, RRID:SCR_002798)
    STATA version 16 (College Station),
    STATA
    suggested: (Stata, RRID:SCR_012763)
    Statistical analyses of global cytokine profiles (pie charts) were performed by partial permutation tests using SPICE.
    SPICE
    suggested: (SPICE, RRID:SCR_016603)

    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: We detected the following sentences addressing limitations in the study:
    This study had some limitations. Half of the study participants in this trial received an investigational Type III IFN at the time of infection. However, in this study, this agent neither shortened the duration of viral shedding nor symptoms (Jagannathan et al., 2021), nor did we observe any significant impact on either innate (Hu et al., 2021) or adaptive (Chakraborty et al., 2021) immune responses between arms, allowing us to utilize data from both arms to improve statistical power. In addition, stratified analyses, and multivariate models adjusted for treatment arm as a covariate, confirmed pooled results. Although we would have liked to have assessed for correlations with protection against reinfection, only one participant had evidence of reinfection during follow-up. Future larger cohorts, and/or case/control designs, will be required to address this question. Finally, we only utilized data assessing responses to the original consensus strain, and do not present data on responses to variants. However, others have recently reported that infection-induced SARS-CoV-2 T cell responses have broad reactivity against viral variant proteins (Keeton et al., 2021; Tarke et al., 2021). By providing insight into the shifting quality of the SARS-CoV-2-specific CD4+ T cell response following infection, how this is impacted by vaccination, and which features most strongly correlate with immune effector mechanisms, our study adds to our growing understanding of the memory T cell respon...

    Results from TrialIdentifier: We found the following clinical trial numbers in your paper:

    IdentifierStatusTitle
    NCT04331899CompletedSingle-Blind Study of a Single Dose of Peginterferon Lambda-…


    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 page 48. 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.

    Results from scite Reference Check: We found no unreliable references.


    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.