Unraveling the relationship between COVID-19 viral load, disease severity, and innate Immune response: insights from mathematical modeling and sensitivity analysis

Iranian Journal of Numerical Analysis and Optimization

مقاله 2، دوره 17، Issue 1 - شماره پیاپی 40، بهار 2027، صفحه 25-44   

نوع مقاله: Research Article

شناسه دیجیتال (DOI): 10.22067/ijnao.2026.99453.1899

نویسندگان

Mehdi Lotfi¹؛ Azizeh Jabbari^{* 2}؛ Reza Rahbarghazi³؛ Hossein Kheiri⁴

¹Institute of Bioinformatics, University Medicine Greifswald, Greifswald, Germany

²Department of Applied Mathematics, Faculty of Mathematical Sciences, University of Tabriz, Tabriz, Iran

³Department of Applied Cell Sciences, Faculty of Advanced Medical Sciences, Tabriz University of Medical Sciences, Tabriz, Iran

⁴Department of Applied Mathematics, Faculty of Mathematical Sciences, University of Tabriz, Tabriz, Iran

چکیده

Coronavirus disease 2019 (COVID-19) created a global health crisis and highlighted the need for a mechanistic understanding of interactions between SARS-CoV-2 and host immune responses. Although numerous mathematical models have described COVID-19 at the epidemiological scale, fewer studies have examined within-host viral dynamics and innate immune mechanisms. In this study, we develop a nonlinear ordinary differential equation model describing interactions among SARS-CoV-2, epithelial cells, resting and activated macrophages, neutrophils, and monocytes. We establish the nonnegativity of solutions, derive the within-host basic reproduction number, and analyze the local and global stability of the COVID-19-free equilibrium. Parameters are calibrated using two clinical datasets representing mild, severe, and intensive care unit (ICU) cases. The calibrated simulations indicate that mild disease is associated with faster viral clearance, more effective immune-mediated viral removal, and better epithelial recovery, whereas severe and ICU cases exhibit delayed clearance, dysregulated neutrophil dynamics, and greater virus-associated immune-cell loss. The corrected normalized sensitivity indices show that viral entry, healthy epithelial-cell renewal, infected-cell lysis, and viral production increase the basic reproduction number, whereas infected-cell recovery, cell loss, and viral clearance reduce it. These findings provide quantitative insight into how innate immune dysregulation may contribute to COVID-19 severity and identify the model mechanisms that most strongly influence within-host viral persistence.

کلیدواژه‌ها

SARS-CoV-2؛ COVID-19؛ Innate immune dynamics؛ Withinhost modeling؛ Sensitivity analysis