论文标题
最佳药物方案和联合药物疗法及其在Covid-19的治疗中的功效:主机内建模研究
Optimal Drug Regimen and Combined Drug Therapy and its Efficacy in the Treatment of COVID-19 : An Within-Host Modeling Study
论文作者
论文摘要
在过去的几个月中,Covid-19-19引起了212个国家的3035万多次感染和9、50、625人死亡。在Covid-19的多个发病机理的多个阶段作用的不同药物干预可以大大降低感染诱导的死亡率。当前的主机内数学建模研究涉及最佳药物方案以及联合治疗在Covid-19的治疗中的功效。所考虑的药物/干预措施包括Arbidol,Remdesivir,Inteferon(Inf)和Lopinavir/Ritonavir。得出的结论是,这些药物干预措施单独服用或组合减少感染细胞和病毒载量。已经讨论了四种涉及单一药物干预,两种药物干预,三种药物干预措施以及所有四种情况的情况。在所有这些情况下,根据两种方法提出了最佳药物方案。在第一种方法中,这些医疗干预措施被建模为控制干预措施,并制定了相应的目标函数和最佳控制问题。在这种情况下,提出了最佳药物方案。后来,使用比较有效性方法根据基本繁殖数和病毒负荷提出了最佳药物方案。当将所有四个干预措施一起应用时,平均感染的细胞计数和病毒载量最大。另一方面,仅当arbidol被施用时,平均易感细胞计数降低了。当将所有四个干预措施一起恢复到最佳控制设置中的早期事实时,基本的繁殖数和病毒计数降低了最佳。这些发现可能有助于医生在治疗威胁生命的19009肺炎方面做出决策。
The COVID-19 pandemic has resulted in more than 30.35 million infections and 9, 50, 625 deaths in 212 countries over the last few months. Different drug intervention acting at multiple stages of pathogenesis of COVID-19 can substantially reduce the infection induced mortality. The current within-host mathematical modeling studies deals with the optimal drug regimen and the efficacy of combined therapy in treatment of COVID-19. The drugs/interventions considered include Arbidol, Remdesivir, Inteferon (INF) and Lopinavir/Ritonavir. It is concluded that these drug interventions when administered individually or in combination reduce the infected cells and viral load. Four scenarios involving administration of single drug intervention, two drug interventions, three drug interventions and all the four have been discussed. In all these scenarios the optimal drug regimen is proposed based on two methods. In the first method these medical interventions are modeled as control interventions and a corresponding objective function and optimal control problem is formulated. In this setting the optimal drug regimen is proposed. Later using the the comparative effectiveness method the optimal drug regimen is proposed based on basic reproduction number and viral load. The average infected cell count and viral load decreased the most when all the four interventions were applied together. On the other hand the average susceptible cell count decreased the best when Arbidol alone was administered. The basic reproduction number and viral count decreased the best when all the four interventions were applied together reinstating the fact obtained earlier in the optimal control setting. These findings may help physicians with decision making in treatment of life-threatening COVID-19 pneumonia.