Burden of cytokines storm on prognosis of SARS-CoV-2 infection through immune response: dynamic analysis and optimal control with immunomodulatory therapy.

Abstract

Immune responses have a crucial role to play against SARS-CoV-2 virus as the adaptive and innate immune systems of the human body help restoring the body to a healthy stage by annihilating this deadly viral infection. Cytokines also play a significant role in modulating a balance between innate and adaptive immune responses but excess of it can have a detrimental affect on critically ill patients. Therefore, this paper is a novel attempt to formulate a within-host mathematical model showing the impact of cytokines storm on healthy cells. The dynamics of the system is analysed which involves basic reproduction number, steady state solutions and global dynamics for disease-free point and endemic equilibrium using geometric approach. Further, an optimal control problem is discussed considering immunomodulatory therapy (targeting cytokines signaling) as control using linear feedback control method to increase the level of healthy cells, which provides vitality for our system. Through numerical simulations, analytic solutions are validated followed by the curve-fit for the cytokines using real data and an optimization algorithm for optimal fit. Finally, sensitivity analysis for the basic reproduction number and the rate of change of healthy cells using Latin Hypercube Sampling method (LHS) is performed. Our finding suggests that immunomodulatory therapy (tocilizumab) can act as a key component to control cytokines storm for critically ill patients to restore the body to a healthy state.