COVID-19急症与重症宿主内动力学建模研究  

Modeling of Within-host Dynamics for Critical and Severe COVID-19 Patients

作　　者：沈俊强 唐旭清[1] SHEN Jun-qiang;TANG Xu-qing(School of Sciences,Jiangnan University,Wuxi 214122,Jiangsu,China)

机构地区：[1]江南大学理学院,中国江苏无锡214122

出　　处：《生命科学研究》2022年第4期291-300,共10页Life Science Research

基　　金：国家自然科学基金资助项目(11371174)。

摘　　要：为了研究COVID-19的宿主内动力学、分析急症患者与重症患者之间的差异,本文提出了一个TCL-IR模型。首先,基于靶细胞限制模型和免疫应答模型构建TCL-IR模型,并获得宿主内再生数的表达式;其次,结合已有研究确定模型中的部分参数,再采用自适应Metropolis算法进行未知参数的估计;最后,根据所得结果对急症、重症患者之间的差异进行分析。结果显示,急症和重症患者在免疫反应和病毒载量上均有一定差别。急症患者的T细胞增殖系数为0.652,免疫凋亡速率为4.137×10^(-6);重症患者的T细胞增殖系数为0.266,免疫凋亡速率为3.283×10^(-6)。急症患者的病毒载量在35 d左右达到峰值,约为7.20×10^(4)copies/mL;重症患者的病毒载量在28 d左右达到峰值且峰值更高,约为1.38×10^(5)copies/mL。根据结果分析和文献印证,研究发现部分急症患者的病情加重并不是因为体内过高的病毒载量,而是因为自身过度的免疫反应。因此,急症患者的治疗需要考虑免疫调节方案。In order to study the within-host dynamics of COVID-19 and analyze the differences between critical and severe patients,a target cell limited-immune response(TCL-IR)model was proposed.Firstly,the TCL-IR model was constructed based on the target cell limited model and the immune response model,and the expression of within-host reproduction number was obtained;secondly,some parameters in the model were determined according to the existing research,and then other unknown parameters were estimated by the adaptive Metropolis algorithm;finally,the differences between critical and severe patients were analyzed according to the obtained results.The results showed some differences in immune response and viral load between critical and severe patients.The T cell proliferation coefficient and immune apoptosis rate were0.652 and 4.137×10^(-6),respectively,in critical patients,and were 0.266 and 3.283×10^(-6),respectively,in severe patients.The viral load in critical patients reached a peak value of 7.20×10^(4)copies/mL around 35 days after infection,and the viral load in severe patients reached a higher peak value of 1.38×10^(5)copies/mL around 28 days.Based on result analysis and literature review,the study found that the severity of some critical patients was not due to a high viral load,but to their own excessive immune response.Therefore,immunomodulatory strategies should be considered in the treatment of critical patients.

关 键 词：严重急性呼吸综合征冠状病毒2(SARS-CoV-2) 宿主内动力学 靶细胞限制模型 免疫应答模型 

分 类 号：O29[理学—应用数学] Q811[理学—数学] R563.1[生物学—生物工程]