Immunological memory to Common Cold Coronaviruses assessed longitudinally over a three-year period

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Abstract

Understanding immune memory to Common Cold Coronaviruses (CCCs) is relevant for assessing its potential impact on the outcomes of SARS-CoV-2 infection, and for the prospects of pan-corona vaccines development. We performed a longitudinal analysis, of pre-pandemic samples collected from 2016-2019. CD4+ T cells and antibody responses specific for CCC and to other respiratory viruses, and chronic or ubiquitous pathogens were assessed. CCC-specific memory CD4+ T cells were detected in most subjects, and their frequencies were comparable to those for other common antigens. Notably, responses to CCC and other antigens such as influenza and Tetanus Toxoid (TT) were sustained over time. CCC-specific CD4+ T cell responses were also associated with low numbers of HLA-DR+CD38+ cells and their magnitude did not correlate with yearly changes in the prevalence of CCC infections. Similarly, spike RBD-specific IgG responses for CCC were stable throughout the sampling period. Finally, high CD4+ T cell reactivity to CCC, but not antibody responses, was associated with high pre-existing SARS-CoV-2 immunity. Overall, these results suggest that the steady and sustained CCC responses observed in the study cohort are likely due to a relatively stable pool of CCC-specific memory CD4+ T cells instead of fast decaying responses and frequent reinfections.

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  1. SciScore for 10.1101/2022.03.01.482548: (What is this?)

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

    Table 1: Rigor

    EthicsConsent: Each participant provided informed consent and was assigned a study identification number with clinical information recorded.
    Sex as a biological variablenot detected.
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot detected.

    Table 2: Resources

    Antibodies
    SentencesResources
    The plate was washed three times using wash buffer (1X TBS containing 0.2% Tween 20), then 50 µL of horseradish peroxidase-conjugated secondary Goat Anti-Human secondary IgG antibody (Cat No: 109-035-008, Jackson ImmunoResearch) at 1:40,000 dilution in 3% milk was added for 1 hour at 37°C.
    Anti-Human secondary IgG
    suggested: None
    Software and Algorithms
    SentencesResources
    Cells were cultured for 20 to 24 hours in the presence of CCC or SARS-CoV-2 specific and other common antigen pools (1ug/ml) in 96-wells U bottom plates with 1×106 PBMC per well.
    SARS-CoV-2
    suggested: (Active Motif Cat# 91351, RRID:AB_2847848)
    All samples were acquired on a ZE5 cell analyzer (Biorad laboratories, Hercules, CA) and analyzed with FlowJo software (Tree Star, Ashland, OR).
    FlowJo
    suggested: (FlowJo, RRID:SCR_008520)
    Statistical analysis: Experimental data were analyzed by GraphPad Prism Version 9 (La Jolla, CA) and Microsoft Excel Version 16.16.27
    GraphPad
    suggested: (GraphPad Prism, RRID:SCR_002798)
    Microsoft Excel
    suggested: (Microsoft Excel, RRID:SCR_016137)

    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:
    Limitations of the study: A limitation of this investigation is the unknown history of previous CCC exposure of the study participants. Assessment of CCC infection by RT-PCR was not part of the original study design for the study, and would also not have been logistically feasible over the longitudinal course of the study as it would have required frequent nasal swabs of all subjects. Therefore, in the present study, the stability of T cell and antibody responses could not be directly correlated with protection from symptomatic colds and/or infection. Furthermore, our analysis is limited to “steady state” responses in adults, and the evolution of CCC responses in children was not addressed. Additional limitations of this study are the relatively small cohort size investigated. Validation of the results in geographically distinct populations would be desirable to generalize the findings broadly.

    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.

    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.