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

TL;DR

This paper introduces a fast, computationally efficient approximation method for hierarchical Bayesian inference of within-host viral dynamics models, enabling analysis of large datasets like COVID-19 viral load data.

Contribution

The authors develop a novel random time-shift approximation that reduces computational costs and allows for hierarchical Bayesian inference on large viral datasets.

Findings

Method runs on a consumer laptop, enabling large-scale analysis.

Successfully applied to COVID-19 viral load data from 163 individuals.

Properly accounts for process noise early in infection.

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 for this class of models 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 datasets and a reanalysis of COVID-19 monitoring data in an National Basketball Association cohort of 163 individuals.