VIBES: A multiscale modeling approach integrating within-host and between-hosts dynamics in epidemics.

Abstract

Infectious disease spread is a multiscale process composed of within-host (biological) and between-host (social) drivers and disentangling them from each other is a central challenge in epidemiology. Here, we introduce VIBES, a multiscale modeling framework that explicitly integrates viral dynamics based on patient-level data with population-level transmission on a data-driven network of social contacts. Using SARS-CoV-2 as a case study, we analyze three emergent epidemic properties, namely the generation time, serial interval, and presymptomatic transmission. First, we established a purely biological baseline, thus independent of the reproduction number (<i>R</i>), from the within-host model, estimating a generation time of 6.3 d for symptomatic individuals and 43.1% presymptomatic transmission. Then, using the full model incorporating social contacts, we found a shorter generation time (5.4 d at <i>R</i> = 3.0) and an increase in presymptomatic transmission (52.8% at <i>R</i> = 3.0), disentangling the impact of social drivers from a purely biological baseline. We further show that as pathogen transmissibility increases (<i>R</i> from 1.3 to 6), competition among infectious individuals shortens the generation time and serial interval by up to 21% and 13%, respectively. Conversely, a social intervention, like isolation, increases the proportion of presymptomatic transmission by about 30%. Our framework also estimates metrics that are challenging to obtain empirically, such as the generation time for asymptomatic individuals (5.6 d; 95%CI: 5.1 to 6.0 at <i>R</i> = 1.3). Our findings establish multiscale modeling as a powerful tool for mechanistically quantifying how pathogen biology and human social behavior shape epidemic dynamics as well as for assessing public health interventions.