A Validated Mathematical Model of the Cytokine Release Syndrome in Severe COVID-19

Ruy Freitas Reis; Alexandre Bittencourt Pigozzo; Carla Rezende Barbosa Bonin; Barbara de Melo Quintela; Lara Turetta Pompei; Ana Carolina Vieira; Larissa de Lima E Silva; Maicom Peters Xavier; Rodrigo Weber Dos Santos; Marcelo Lobosco

doi:10.3389/fmolb.2021.639423

A Validated Mathematical Model of the Cytokine Release Syndrome in Severe COVID-19

Front Mol Biosci. 2021 Jul 20:8:639423. doi: 10.3389/fmolb.2021.639423. eCollection 2021.

Authors

Affiliations

¹ Institute of Exact Sciences, Department of Computing, Federal University of Juiz de Fora, Juiz de Fora, Brazil.
² FISIOCOMP - Laboratory of Computational Fisiology and High-Performance Computing, Federal University of Juiz de Fora, Juiz de Fora, Brazil.
³ Computer Science Department, Federal University of São João Del-Rei, São João Del-Rei, Brazil.
⁴ Institute of Education, Science and Technology of Southeast of Minas Gerais - Cataguases Advanced Campus, Cataguases, Brazil.
⁵ GET-EngComp, Grupo de Educação Tutorial Engenharia Computacional, Federal University of Juiz de Fora, Juiz de Fora, Brazil.
⁶ Graduate Program on Computational Modeling, Federal University of Juiz de Fora, Juiz de Fora, Brazil.

Abstract

By June 2021, a new contagious disease, the Coronavirus disease 2019 (COVID-19), has infected more than 172 million people worldwide, causing more than 3.7 million deaths. Many aspects related to the interactions of the disease's causative agent, SAR2-CoV-2, and the immune response are not well understood: the multiscale interactions among the various components of the human immune system and the pathogen are very complex. Mathematical and computational tools can help researchers to answer these open questions about the disease. In this work, we present a system of fifteen ordinary differential equations that models the immune response to SARS-CoV-2. The model is used to investigate the hypothesis that the SARS-CoV-2 infects immune cells and, for this reason, induces high-level productions of inflammatory cytokines. Simulation results support this hypothesis and further explain why survivors have lower levels of cytokines levels than non-survivors.

Keywords: COVID-19; SARS-CoV-2; citokine storm; computational immunology; mathematical modelling; sensitivity analysis.