Data-driven multi-scale mathematical modeling of SARS-CoV-2 infection reveals heterogeneity among COVID-19 patients.
Shun WangMengqian HaoZishu PanJinzhi LeiXiufen ZouPublished in: PLoS computational biology (2021)
Patients with coronavirus disease 2019 (COVID-19) often exhibit diverse disease progressions associated with various infectious ability, symptoms, and clinical treatments. To systematically and thoroughly understand the heterogeneous progression of COVID-19, we developed a multi-scale computational model to quantitatively understand the heterogeneous progression of COVID-19 patients infected with severe acute respiratory syndrome (SARS)-like coronavirus (SARS-CoV-2). The model consists of intracellular viral dynamics, multicellular infection process, and immune responses, and was formulated using a combination of differential equations and stochastic modeling. By integrating multi-source clinical data with model analysis, we quantified individual heterogeneity using two indexes, i.e., the ratio of infected cells and incubation period. Specifically, our simulations revealed that increasing the host antiviral state or virus induced type I interferon (IFN) production rate can prolong the incubation period and postpone the transition from asymptomatic to symptomatic outcomes. We further identified the threshold dynamics of T cell exhaustion in the transition between mild-moderate and severe symptoms, and that patients with severe symptoms exhibited a lack of naïve T cells at a late stage. In addition, we quantified the efficacy of treating COVID-19 patients and investigated the effects of various therapeutic strategies. Simulations results suggested that single antiviral therapy is sufficient for moderate patients, while combination therapies and prevention of T cell exhaustion are needed for severe patients. These results highlight the critical roles of IFN and T cell responses in regulating the stage transition during COVID-19 progression. Our study reveals a quantitative relationship underpinning the heterogeneity of transition stage during COVID-19 progression and can provide a potential guidance for personalized therapy in COVID-19 patients.
Keyphrases
- sars cov
- respiratory syndrome coronavirus
- coronavirus disease
- end stage renal disease
- immune response
- chronic kidney disease
- single cell
- ejection fraction
- dendritic cells
- newly diagnosed
- peritoneal dialysis
- early onset
- drug induced
- high resolution
- metabolic syndrome
- high intensity
- molecular dynamics
- endothelial cells
- type diabetes
- patient reported outcomes
- skeletal muscle
- case report
- cell death
- reactive oxygen species
- electronic health record
- big data
- cell proliferation
- smoking cessation
- diabetic rats
- cell cycle arrest
- patient reported