Innate Immunity Plays a Key Role in Controlling Viral Load in COVID-19: Mechanistic Insights from a Whole-Body Infection Dynamics Model
Prashant Dogra, Javier Ruiz-Ramírez, Kavya Sinha, Joseph D. Butner, María J. Peláez, Manmeet Rawat, Venkata Yellepeddi, Renata Pasqualini, Wadih Arap, H. Dirk Sostman, Vittorio Cristini, Zhihui Wang
Abstract
and clinical data, we used the model to simulate viral load progression in a virtual patient with varying degrees of compromised immune status. Further, we ranked model parameters through sensitivity analysis for their significance in governing clearance of viral load to understand the effects of physiological factors and underlying conditions on viral load dynamics. Antiviral drug therapy, interferon therapy, and their combination were simulated to study the effects on viral load kinetics of SARS-CoV-2. The model revealed the dominant role of innate immunity (specifically interferons and resident macrophages) in controlling viral load, and the importance of timing when initiating therapy after infection.