COVID-19 virtual patient cohort suggests immune mechanisms driving disease outcomes.

To understand the diversity of immune responses to SARS-CoV-2 and distinguish features that predispose individuals to severe COVID-19, we developed a mechanistic, within-host mathematical model and virtual patient cohort. Our results suggest that virtual patients with low production rates of infected cell derived IFN subsequently experienced highly inflammatory disease phenotypes, compared to those with early and robust IFN responses. In these in silico patients, the maximum concentration of IL-6 was also a major predictor of CD8+ T cell depletion.

COVID-19 virtual patient cohort reveals immune mechanisms driving disease outcomes.

Unlabelled: To understand the diversity of immune responses to SARS-CoV-2 and distinguish features that predispose individuals to severe COVID-19, we developed a mechanistic, within-host mathematical model and virtual patient cohort. Our results indicate that virtual patients with low production rates of infected cell derived IFN subsequently experienced highly inflammatory disease phenotypes, compared to those with early and robust IFN responses. In these patients, the maximum concentration of IL-6 was also a major predictor of CD8 T cell depletion.

Translational approaches to treating dynamical diseases through in silico clinical trials.

The primary goal of drug developers is to establish efficient and effective therapeutic protocols. Multifactorial pathologies, including dynamical diseases and complex disorders, can be difficult to treat, given the high degree of inter- and intra-patient variability and nonlinear physiological relationships. Quantitative approaches combining mechanistic disease modeling and computational strategies are increasingly leveraged to rationalize pre-clinical and clinical studies and to establish effective treatment strategies.