Comparing antiviral strategies against COVID-19 via multiscale within-host modelling

TL;DR

This study develops a multiscale within-host model of COVID-19 to evaluate antiviral and convalescent plasma therapies, revealing that early combined treatment is most effective but may prolong infection if delayed.

Contribution

It introduces a novel multiscale stochastic agent-based and ODE model of COVID-19 infection dynamics, integrating immune response and treatment effects.

Findings

Combined antiviral and plasma therapy reduces infection duration effectively.

Delayed treatment diminishes the synergistic benefits of combined therapies.

Early treatment with single therapies may prolong infection in some cases.

Abstract

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.