Mathematical modeling of SARS-CoV-2 viral dynamics and treatment with monoclonal antibodies

SARS-CoV-2病毒动力学的数学建模及单克隆抗体治疗

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Abstract

The novel coronavirus (SARS-CoV-2) affects primarily the respiratory tract, and if left unchecked can cause a spectrum of pathological manifestations such as pneumonia, acute respiratory distress syndrome, myocardial injury, thromboembolism, and acute kidney injury. Medication strategies have involved minimizing the spread of the virus through antiviral medications (monoclonal antibodies or nucleotide reverse transcriptase inhibitors). Here, we develop a mathematical model that simulates viral dynamics in an untreated individual, and the evaluate the impact that a monoclonal antibody can have on slowing viral replication. Drug pharmacokinetics (PK) was informed by a typical two-compartment PK model with parameters typical of a monoclonal antibody, with a third compartment for the lung included as the drug site of action. The viral dynamics were captured using a simplified model describing uninfected target cells, infected target cells, and viral load in the body. The mechanism of action of the simulated antiviral is based on binding to the virus, thereby preventing it from infecting healthy cells. The model is used to project dosages needed to prevent severe disease under a variety of simulated conditions and subject to realistic constraints. The proposed model can capture a variety of scenarios of longitudinal viral dynamics and assess the impact of antiviral therapy on disease severity and duration. The described approach can be easily adapted to rapidly assess the dosages needed to affect duration and outcome of other viral infections and can serve as part of a fast and efficient scientific and modeling response strategy in the future as needed.

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