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
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
复制标题
DOI：
10.1101/2022.05.06.490883
复制
发表时间：
2022-05
期刊：
影响因子：
--
通讯作者：
Christopher F. Rowlatt;Mark A. J. Chaplain;D. Hughes;S. Gillespie;D. Dockrell;I. Johannessen;R. Bowness
中科院分区：
文献类型：
--
作者：
Christopher F. Rowlatt;Mark A. J. Chaplain;D. Hughes;S. Gillespie;D. Dockrell;I. Johannessen;R. Bowness
个体对SARS-CoV-2感染的反应差异很大，从不需要住院的轻度感染过程到不仅需要住院但可能致命的疾病发展。虽然许多免疫学研究揭示了SARS-CoV-2感染和COVID-19的基本见解，但数学和计算模型可以提供额外的视角并增强理解。大多数SARS-CoV-2感染的宿主内传播的数学模型是常微分方程，忽略了空间变化。在这篇文章中，我们提出了一个混合的，多尺度的，基于个体的模型来研究SARS-CoV-2感染的宿主内传播。该模型包括上皮细胞（每个细胞包含病毒进入和复制的动态模型），巨噬细胞和细胞因子的子集。我们调查的作用，增加初始病毒沉积，增加延迟I型干扰素分泌上皮细胞（以及分泌的幅度），增加巨噬细胞病毒内化率和巨噬细胞活化，感染的传播。
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.