Random time-shift approximation enables hierarchical Bayesian inference of mechanistic within-host viral dynamics models on large datasets

Abstract: Mechanistic mathematical models of within-host viral dynamics are tools for understanding how a virus' biology and its interaction with the immune system shape the infectivity of a host. The biology of the process is encoded by the structure and parameters of the model that can be inferred statistically by fitting to viral load data. The main drawback of mechanistic models is that this inference is computationally expensive because the model must be repeatedly solved. This limits the size of the datasets that can be considered or the complexity of the models fitted. In this paper we develop a much cheaper inference method by implementing a novel approximation of the model dynamics that uses a combination of random and deterministic processes. This approximation also properly accounts for process noise early in the infection when cell and virion numbers are small, which is important for the viral dynamics but often overlooked. Our method runs on a consumer laptop and is fast enough to facilitate a full hierarchical Bayesian treatment of the problem with sharing of information to allow for individual level parameter differences. We apply our method to simulated data and a reanalysis of COVID-19 monitoring data in an National Basketball Association cohort of 163 individuals.