Optimal Drug Regimen and Combined Drug Therapy and Its Efficacy in the Treatment of COVID-19: A Within-Host Modeling Study.

The COVID-19 pandemic has resulted in more than 524 million cases and 6 million deaths worldwide. Various drug interventions targeting multiple stages of COVID-19 pathogenesis can significantly reduce infection-related mortality. The current within-host mathematical modeling study addresses the optimal drug regimen and efficacy of combination therapies in the treatment of COVID-19. The drugs/interventions considered include Arbidol, Remdesivir, Interferon (INF) and Lopinavir/Ritonavir. It is concluded that these drugs, when administered singly or in combination, reduce the number of infected cells and viral load. Four scenarios dealing with the administration of a single drug, two drugs, three drugs and all four are 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 are formulated. In this framework, the optimal drug regimen is derived. Later, using the comparative effectiveness method, the optimal drug regimen is derived based on the basic reproduction number and viral load. The average number of infected cells and viral load decreased the most when all four drugs were used together. On the other hand, the average number of susceptible cells decreased the most when Arbidol was administered alone. The basic reproduction number and viral load decreased the most when all four interventions were used together, confirming the previously obtained finding of the optimal control problem. The results of this study can help physicians make decisions about the treatment of the life-threatening COVID-19 infection.

Optimal Control Studies on Age Structured Modeling of COVID-19 in Presence of Saturated Medical Treatment of Holling Type III.

COVID-19 pandemic has caused the most severe health problems to adults over 60 years of age, with particularly fatal consequences for those over 80. In this case, age-structured mathematical modeling could be useful to determine the spread of the disease and to develop a better control strategy for different age groups. In this study, we first propose an age-structured model considering two different age groups, the first group with population age below 30 years and the second with population age above 30 years, and discuss the stability of the equilibrium points and the sensitivity of the model parameters. In the second part of the study, we propose an optimal control problem to understand the age-specific role of treatment in controlling the spread of COVID -19 infection. From the stability analysis of the equilibrium points, it was found that the infection-free equilibrium point remains locally asymptotically stable when R 0 < 1 , and when R 0 is greater than one, the infected equilibrium point remains locally asymptotically stable. The results of the optimal control study show that infection decreases with the implementation of an optimal treatment strategy, and that a combined treatment strategy considering treatment for both age groups is effective in keeping cumulative infection low in severe epidemics. Cumulative infection was found to increase with increasing saturation in medical treatment.

Additional Food Supplements as a Tool for Biological Conservation of Biosystems in the Presence of Inhibitory Effect of the Prey.

Provision of additional food supplements for the purpose of biological conservation has been widely researched both theoretically and experimentally. The study of these biosystems is usually done using predator-prey models. In this paper, we consider an additional food provided predator-prey system in the presence of the inhibitory effect of the prey. This model is analyzed in the control parameter space using the control parameters, quality and quantity of additional food. The findings suggest that with appropriate choice of additional food to predators, the biosystem can be controlled and steered to a desirable state. It is also possible to eliminate either of the interacting species. The vital role of the quality and quantity of the additional food in the system dynamics cautions the eco manager on the choice of the additional food for realizing the goal in the biological conservation programme.