Modelling Infection and Immunity Lab, Mathematics and Statistics, York University, 4700 Keele St, Toronto, M3J 1P3, ON, Canada; Centre for Disease Modelling, Mathematics and Statistics, York University, 4700 Keele St, Toronto, M3J 1P3, ON, Canada.
Department of Mathematics and Computer Science, Mount Allison University, 62 York St, Sackville, E4L 1E2, NB, Canada.
J Theor Biol. 2023 May 7;564:111449. doi: 10.1016/j.jtbi.2023.111449. Epub 2023 Mar 7.
Within-host SARS-CoV-2 modelling studies have been published throughout the COVID-19 pandemic. These studies contain highly variable numbers of individuals and capture varying timescales of pathogen dynamics; some studies capture the time of disease onset, the peak viral load and subsequent heterogeneity in clearance dynamics across individuals, while others capture late-time post-peak dynamics. In this study, we curate multiple previously published SARS-CoV-2 viral load data sets, fit these data with a consistent modelling approach, and estimate the variability of in-host parameters including the basic reproduction number, R, as well as the best-fit eclipse phase profile. We find that fitted dynamics can be highly variable across data sets, and highly variable within data sets, particularly when key components of the dynamic trajectories (e.g. peak viral load) are not represented in the data. Further, we investigated the role of the eclipse phase time distribution in fitting SARS-CoV-2 viral load data. By varying the shape parameter of an Erlang distribution, we demonstrate that models with either no eclipse phase, or with an exponentially-distributed eclipse phase, offer significantly worse fits to these data, whereas models with less dispersion around the mean eclipse time (shape parameter two or more) offered the best fits to the available data across all data sets used in this work. This manuscript was submitted as part of a theme issue on "Modelling COVID-19 and Preparedness for Future Pandemics".
在整个 COVID-19 大流行期间,已经发表了许多关于 SARS-CoV-2 宿主内建模的研究。这些研究包含了数量变化极大的个体,并捕获了病原体动力学的不同时间尺度;一些研究捕获了疾病发作的时间、病毒载量峰值以及随后个体清除动力学的异质性,而另一些研究则捕获了峰值后后期的动力学。在这项研究中,我们整理了多个先前发表的 SARS-CoV-2 病毒载量数据集,使用一致的建模方法对这些数据进行拟合,并估计了宿主内参数的可变性,包括基本繁殖数 R 以及最佳拟合的隐伏期分布。我们发现,拟合动力学在数据集之间可能存在很大差异,并且在数据集内也存在很大差异,尤其是当动态轨迹的关键组成部分(例如病毒载量峰值)未在数据中表示时。此外,我们研究了隐伏期时间分布在拟合 SARS-CoV-2 病毒载量数据中的作用。通过改变爱尔朗分布的形状参数,我们证明了没有隐伏期或具有指数分布隐伏期的模型对这些数据的拟合效果明显较差,而具有更接近平均值隐伏时间(形状参数为 2 或更多)的模型对所有用于这项工作的数据集的可用数据提供了最佳拟合。本文是作为关于“COVID-19 建模和为未来大流行做准备”主题专刊的一部分提交的。