A modular model of immune response as a computational platform to investigate a pathogenesis of infection disease

Abstract

The COVID-19 pandemic significantly transformed the field of mathematical modeling in immunology. International collaboration among numerous research groups yielded a substantial amount of experimental data, which greatly facilitated model validation and led to the development of new mathematical models. The aim of the study is an improvement of system understanding of the immune response to SARS-CoV-2 infection based on the development of a modular mathematical model which provides a foundation for further research on host-pathogen interactions. We utilized the open-source BioUML platform to develop a model using ordinary, delay and stochastic differential equations. The model was validated using experimental data from middle-aged individuals with moderate COVID-19 progression, including measurements of viral load, antibodies, CD4+ and CD8+ T cells, and interleukin-6 levels. Parameter optimization and sensitivity analysis were conducted to refine the models accuracy. The model effectively reproduces moderate, severe, and critical COVID-19 progressions, consistent with experimental observations. We investigated the efficiency and contributions of innate and adaptive immunity in response to SARS-CoV-2 infection and assessed immune system behavior during co-infection with HIV and organ transplantation. Additionally, we studied therapy methods, such as interferon administration. The developed model can be employed as a framework for simulating other infectious diseases taking into account follow-up immune response. Author summaryDespite the significant progress reached in understanding of COVID-19, traditional methods still struggle to analyze and interpret the extensive and sometimes controversial experimental data on SARS-CoV-2 infection. Mathematical and systems biology approaches attempt to address this challenge by developing mathematical models of the immune response. We aimed not only to investigate the disease at a systemic level but also to provide a framework for further research on host-pathogen interactions, both existing and forthcoming. To achieve this, we constructed a model incorporating both innate and adaptive immunity, as well as cellular and humoral components. This together allowed us to conduct a series of in silico experiments, exploring the immune response across various levels and compartments. The results of these investigations offer valuable insights into the complex dynamics of the immune system and can guide future research and therapeutic strategies.