Modelling the within-host spread of SARS-CoV-2 infection, and the subsequent immune response, using a hybrid, multiscale, individual-based model. Part I: Macrophages

  1. C. F. Rowlatt
  2. M. A. J. Chaplain
  3. D. J. Hughes
  4. S. H. Gillespie
  5. D. H. Dockrell
  6. I. Johannessen
  7. R. Bowness

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Abstract

Individual responses to SARS-CoV-2 infection vary significantly, ranging from mild courses of infection that do not require hospitalisation to the development of disease which not only requires hospitalisation but can be fatal. Whilst many immunological studies have revealed fundamental insights into SARS-CoV-2 infection and COVID-19, mathematical and computational modelling can offer an additional perspective and enhance understanding. The majority of mathematical models for the within-host spread of SARS-CoV-2 infection are ordinary differential equations, which neglect spatial variation. In this article, we present a hybrid, multiscale, individual-based model to study the within-host spread of SARS-CoV-2 infection. The model incorporates epithelial cells (each containing a dynamical model for viral entry and replication), macrophages and a subset of cytokines. We investigate the role of increasing initial viral deposition, increasing delay in type I interferon secretion from epithelial cells (as well as the magnitude of secretion), increasing macrophage virus internalisation rate and macrophage activation, on the spread of infection.

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  1. ScreenIT

    SciScore for 10.1101/2022.05.06.490883: (What is this?)

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

    Table 1: Rigor

    Ethicsnot detected.
    Sex as a biological variablenot detected.
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot detected.

    Table 2: Resources

    No key resources detected.

    Results from OddPub: Thank you for sharing your data.

    Results from LimitationRecognizer: We detected the following sentences addressing limitations in the study:
    4.1 Limitations of this study: The presented model has several limitations: (1) we assume only a single immune cell population, with only a single phenotype; (2) we assume that macrophages may only activate via a single (classical) route; (3) healthy epithelial cells and resting macrophages do not produce cytokines; (4) only a limited set of cytokines is considered; and finally (5) there is a fair amount of uncertainty surrounding the parameter values. Mathematical and computational models require initial simplification, as well as subsequent iterative development, but can never-the-less, offer a unique perspective that can help enhance understanding. Therefore, the presented model serves as an initial starting point from which we can build, by including further complexity and more detailed study which can inform or enhance experimental studies.

    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

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  2. Version published to 10.1101/2022.05.06.490883v1 on bioRxiv