Optimal Drug Regimen and Combined Drug Therapy and its Efficacy in the Treatment of COVID-19 : An Within-Host Modeling Study

TL;DR

This study uses within-host mathematical modeling to identify optimal drug combinations for COVID-19 treatment, demonstrating that combined therapy significantly reduces viral load and infected cells, aiding clinical decision-making.

Contribution

It introduces a novel within-host modeling approach to evaluate and optimize combined drug regimens for COVID-19, incorporating optimal control and effectiveness analysis.

Findings

All four drug interventions together most effectively reduce viral load.

Arbidol alone best decreases susceptible cell count.

Combined therapy significantly lowers infected cells and viral load.

Abstract

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.