Team:SMMU-China/Model

Overview

Mathematical models are playing an important role that act as a bridge between the theoretical and the clinical realization of our biological work. We aim to develop mathematical models to suggest future CAR-macrophages therapy by stimulating the interaction between the virus, cells and immune responses.

Part 1 SARS-CoV-2 infection viral dynamics model

Aim: To shows the distinct stages of viral dynamics of SARS-CoV-2 infection.

Methods: ODE, Data fitting, Comparison

Part 2 CAR-macrophages activation model

Aim: To stimulate the activation of CAR-macrophages by a dynamic response to SARS-CoV-2.

Methods: ODE, Numerical simulation

Part 3 In vivo antiviral model

Aim: To predict our method on human body, and provide a treatment model.

Modeling the viral dynamics of SARS-CoV-2 infection

We develop a model to study the viral dynamics of SARS-CoV-2 infection.

ASSUMPTION:

1. Pneumocytes are the primary target of infection, lymphocytes are the secondary target of infection.

2. The infected cells produce coronaviruses at a constant rate . The virus is cleared at a constant rate.

3. To fit data more simple , the proliferation and death of pneumocytes are not included.

4. The concentration of lymphocytes is proportional to the innate immune response.

Describe the infection process

T1: The concentration of pneumocytes

T2: The concentration of lymphocytes

We use a constant rate 𝜆 to represent the recruitment of lymphocytes to the infection site due to the lung inflammatory response. Lymphocytes and pneumocytes are infected by the virus at the same rate 𝛽.

Describe immune response of the lung microenvironment：

We set as the population of infected cells, namely infected pneumocytes and lymphocytes to show the severity of the condition. The immune response consists of innate immunity and adaptive immunity. Adaptive immune response is activated after days. is the initial clearance rate of the virus. With the activation of adaptive immunity, the virus clearance rate increases exponentially.

Describe Cytokine release:

Assuming that the dynamic behavior of cytokine release,is related to Virus load and the population of lymphocytes. is defined as the maximum cytokine production rate, and shows the effect of lymphocytes activity on cytokine production. On the other hand, defined in function of the effect of Virus load, assuming that viral decay exerts an fixed rate influence on cytokine decline.