Initial Inoculum and the Severity of COVID-19: A Mathematical Modeling Study of the Dose-Response of SARS-CoV-2 Infections

SARS-CoV-2 (Severe acute respiratory syndrome coronavirus 2) causes a variety of responses in those who contract the virus, ranging from asymptomatic infections to acute respiratory failure and death. While there are likely multiple mechanisms triggering severe disease, one potential cause of severe disease is the size of the initial inoculum. For other respiratory diseases, larger initial doses lead to more severe outcomes. We investigate whether there is a similar link for SARS-CoV-2 infections using the combination of an agent-based model (ABM) and a partial differential equation model (PDM). We use the model to examine the viral time course for different sizes of initial inocula, generating dose-response curves for peak viral load, time of viral peak, viral growth rate, infection duration, and area under the viral titer curve. We find that large initial inocula lead to short infections, but with higher viral titer peaks; and that smaller initial inocula lower the viral titer peak, but make the infection last longer.