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A Multicompartment Mathematical Model Based on Host Immunity for Dissecting COVID-19 Heterogeneity
31 Pages Posted: 31 Jan 2022 Publication Status: Published
Abstract
The determinants underlying the heterogeneity of coronavirus disease 2019 (COVID-19) remain to be elucidated. To systemically analyze the immunopathogenesis of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, we built a multicompartment mathematical model based on immunological principles and typical COVID-19-related characteristics. This model integrated the trafficking of immune cells and cytokines among the secondary lymphoid organs, peripheral blood and lungs. Our results suggested that early-stage lymphopenia was related to lymphocyte chemotaxis, while prolonged lymphopenia in critically ill patients was associated with myeloid-derived suppressor cells. Furthermore, our model predicted that insufficient SARS-CoV-2-specific naïve T/B cell pools and ineffective activation of antigen-presenting cells (APCs) would cause delayed immunity activation, resulting in elevated viral load, low immunoglobulin level, etc. Overall, we provided a comprehensive view of the dynamics of host immunity after SARS-CoV-2 infection that enabled us to understand COVID-19 heterogeneity from systemic perspective.
Funding: This work was supported by the National Key R&D Program in China (Grants No. 2020YFC0845700, No. 2018YFA0900200 and No. 2020YFA0906900), the National Natural Science Foundation of China (Grants No. 12174007 and No. 12090054), Scientific Research Projects of the Chinese Academy of Engineering (Grant No. 2020-KYGG-01-07) and Fundamental Research Funds for the Central Universities (Grant No. 2020kfyXGYJ029).
Declaration of Interests: The authors have declared that no conflict of interest exists.
Ethics Approval Statement: This study was conducted in accordance with the Declaration of Helsinki and was approved by the Ethics Committee of Union Hospital, Tongji Medical College, Huazhong University of Science and Technology (#2020/0004). Written informed consent was waived owing to the emergence of this high-risk infectious disease.
Keywords: mathematical model, COVID-19, heterogeneity, dynamics of host immunity
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