Within-host mathematical modeling on crucial inflammatory mediators and drug interventions in COVID-19 identifies combination therapy to be most effective and optimal.

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From: Alexandria Engineering Journal(Vol. 60, Issue 2)
Publisher: Elsevier B.V.
Document Type: Report
Length: 409 words

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Keywords Covid-19; Inflammatory mediators; Drug interventions; Optimal control problems Abstract The unprecedented Covid-19 pandemic has resulted in more than 14.75 million infections and 6, 10, 839 deaths in 212 countries. Appropriate interventions can decrease the rate of Covid-19 related mortality. Fast track clinical trials around the world are addressing the efficacy of individual pharmaceutical agent acting at various stages of pathogenesis. However, lessons learnt while dealing with past viral epidemics mandates, simultaneous use of such drugs in combination amongst different populations. Mathematical modelling studies can be extremely helpful in understanding the efficacy of drugs both individually and in combination. The current within-host mathematical model studies the natural history of Covid-19 in terms of complex interplay of virus replication and behaviour of host immune response. Additionally it studies the role of various drugs at various stages of pathogenesis. The model was validated by generating two-parameter heat plots, representing the characteristics of Covid-19, the sensitivity analysis identified the crucial parameters. The efficacy of interventions was assessed by optimal control problem. The model dynamics exhibited disease-free equilibrium and the infected equilibrium with their stability, based on the reproduction number R.sub.0, the transcritical bifurcation observed at R.sub.0=1. The burst rate and the natural death rate of the virus were observed as most significant parameters in the life-threatening Covid-19 pneumonia. The antiviral drugs affecting viral replication and those modulating the immune response, reduce the infected cells and viral load significantly. However, the yield was optimal and most effective when the combination therapy involving one or more antiviral and one or more immunomodulating drugs were administered together. These findings may help physicians with early decision making in treatment of life-threatening Covid-19 infection. Author Affiliation: (a) Department of Mathematics and Computer Science, Sri Sathya Sai Institute of Higher Learning - SSSIHL, India (b) Central Leprosy Teaching and Research Institute - CLTRI, Chennai, India (c) Sri Sathya Sai Higher Secondary School - SSSHSS, Puttaparthi, India (d) Sri Sathya Sai Institute of Higher Learning - SSSIHL, India (e) Department of Medicine, Karolinska Institute, Stockholm, Sweden * Corresponding author. Article History: Received 21 July 2020; Revised 20 November 2020; Accepted 10 December 2020 (footnote)[white star] Peer review under responsibility of Faculty of Engineering, Alexandria University. (footnote)1 Joint First Authors. (footnote)2 Joint First Authors. Byline: Bishal Chhetri [bishalchhetri@sssihl.edu.in] (a,1), Vijay M. Bhagat [vijaydr100@gmail.com] (b,2), D.K.K. Vamsi [dkkvamsi@sssihl.edu.in] (a,*), V.S. Ananth [ananthvs@sssihl.edu.in] (a), Bhanu Prakash D [prakashdmacs@gmail.com] (a), Roshan Mandale [roshanmandale1996@gmail.com] (c), Swapna Muthusamy [swapnamuthuswamy@gmail.com] (b), Carani B Sanjeevi [sanjeevi.carani@sssihl.edu.in] (d,e)

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Gale Document Number: GALE|A652397512