Document Type : Research Article
Authors
1
Institute of Bioinformatics, University Medicine Greifswald, Greifswald, Germany
2
Department of Applied Mathematics, Faculty of Mathematical Sciences, University of Tabriz, Tabriz, Iran
3
Department of Applied Cell Sciences, Faculty of Advanced Medical Sciences, Tabriz University of Medical Sciences, Tabriz, Iran
10.22067/ijnao.2026.99453.1899
Abstract
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.
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