A multicompartment mathematical model based on host immunity for dissecting COVID-19 heterogeneity
Jianwei Li,
Jianghua Wu,
Jingpeng Zhang,
Lu Tang,
Heng Mei,
Yu Hu,
Fangting Li
Affiliations
Jianwei Li
School of Physics, Center for Quantitative Biology, Peking University, Beijing 100871, China
Jianghua Wu
Institute of Hematology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China; Hubei Clinical Medical Center of Cell Therapy for Neoplastic Disease, Wuhan, 430022, China
Jingpeng Zhang
School of Physics, Center for Quantitative Biology, Peking University, Beijing 100871, China
Lu Tang
Institute of Hematology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China; Hubei Clinical Medical Center of Cell Therapy for Neoplastic Disease, Wuhan, 430022, China
Heng Mei
Institute of Hematology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China; Hubei Clinical Medical Center of Cell Therapy for Neoplastic Disease, Wuhan, 430022, China; Corresponding author.
Yu Hu
Institute of Hematology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China; Hubei Clinical Medical Center of Cell Therapy for Neoplastic Disease, Wuhan, 430022, China; Corresponding author.
Fangting Li
School of Physics, Center for Quantitative Biology, Peking University, Beijing 100871, China; Corresponding author.
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.
