论文标题
通过多尺度建模比较抗病毒策略与COVID-19
Comparing antiviral strategies against COVID-19 via multiscale within-host modelling
论文作者
论文摘要
COVID-19感染动力学的主宿主模型使各种患者可以评估不同形式的抗病毒治疗的优点。这里引入了基于随机剂的COVID-19的基于随机剂模型,其中包含了治疗选择针对的病毒生命周期的基本步骤。模型预测与宿主内感染动态的细胞间ode模型的整合,该模型适合患者数据,在没有治疗的情况下恢复了疾病进展的通用概况。这与与免疫反应有关的模型参数变化后获得的曲线形成对比,例如效应细胞和抗体增殖率,模仿了免疫功能低下的患者的疾病进展。然后将这些特征与抗病毒和康复血浆治疗相对于COVID-19感染的疾病进展进行比较。该模型表明,在组合中使用两种疗法都可以非常有效地减少感染的长度,但是随着治疗延迟的开始,这些协同作用下降了。相反,单独使用任何一种治疗的早期治疗实际上可以增加感染的持续时间,在其他感染标志物下降之后,感染性病毒仍然存在。这表明这些治疗方法应在临床环境中仔细控制。
Within-host models of COVID-19 infection dynamics enable the merits of different forms of antiviral therapy to be assessed in individual patients. A stochastic agent-based model of COVID-19 intracellular dynamics is introduced here, that incorporates essential steps of the viral life cycle targeted by treatment options. Integration of model predictions with an intercellular ODE model of within-host infection dynamics, fitted to patient data, generates a generic profile of disease progression in patients that have recovered in the absence of treatment. This is contrasted with the profiles obtained after variation of model parameters pertinent to the immune response, such as effector cell and antibody proliferation rates, mimicking disease progression in immunocompromised patients. These profiles are then compared with disease progression in the presence of antiviral and convalescent plasma therapy against COVID-19 infections. The model reveals that using both therapies in combination can be very effective in reducing the length of infection, but these synergistic effects decline with a delayed treatment start. Conversely, early treatment with either therapy alone can actually increase the duration of infection, with infectious virions still present after the decline of other markers of infection. This suggests that usage of these treatments should remain carefully controlled in a clinical environment.