Telomere-length dependent T-cell clonal expansion: A model linking ageing to COVID-19 T-cell lymphopenia and mortality

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Abstract

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  1. SciScore for 10.1101/2021.05.19.21257474: (What is this?)

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

    Table 1: Rigor

    Ethicsnot detected.
    Sex as a biological variableThe combined male and female hazards ratios relative to age 20 in Fig.
    RandomizationIn Fig. 3a, the T-cell TL distribution for age 20 was derived from 1,000,000 random generations from a normal distribution with a mean = 7.3 kb and SD = 0.6 kb.
    Blindingnot detected.
    Power Analysisnot detected.

    Table 2: Resources

    No key resources detected.


    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:
    We acknowledge the following limitations: Our model is deterministic with fixed rates and thresholds selected as best estimates from available literature. That said, analysis of the effects of assumptions on the LCS definition and uncertainty in the parameters r, g, TLB and Δmax indicate that the TLO and XO exhibit little error from the LCS assumption and parameter uncertainties. (Supplementary Information B2). The model draws on HCTL data from populations comprising principally whites of European ancestry in high-income countries. It should also be tested in populations of different ancestries and in low- and middle-income countries. The TL difference between naïve T cells and memory T cells likely reflects the clonal expansion in response to not only a single encounter but multiple encounters with a given antigen and its cross-reactive antigens. Thus, the MCS and LCS definitions in absolute T-cell numbers might be off the mark. Of note, however, the MCS and LCS can be expressed in the model in relative units of MCS (i.e., 0.5 MCS, 0.25 MCS, etc.) rather than absolute units (i.e., 0.5 × 106, 0.25 × 106 T cells, etc.), yielding identical results to those based on absolute T-cell numbers. Therefore, the principles of our model are likely to hold notwithstanding the above limitations. In conclusion, the age-dependent TL effect on naïve T-cell clonal expansion likely influences the outcome of SARS-CoV-2 infection. The insight generated by our model might set the stage for measur...

    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.


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