MSC.BM Theses and Dissertations (2022)

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    COVID-19 viral - host interaction dynamics and immune response
    (Strathmore University, 2022) Kaumbutha, Charles Mwangi
    Even as the world eases into the COVID-19 pandemic, new variants of the virus keep sprouting and destabilizing normal routines. Initially, to arrest the high transmission of SARS CoV-2, non-pharmaceutical approaches were utilised simply for damage control as other interventions such as development of vaccines were being explored. Fortunately, the urgency to control the crisis prompted the vaccine development process to be expedited. Concurrently, Food and Drug Administration (FDA) approved the use of Remdesivir to treat specific demographics of COVID-19 patients. Despite these measures, progressive studies are still providing fresh knowledge. Quantitative approaches have therefore provided useful insights in understanding key aspects of SARS CoV-2. We developed and analysed a mathematical model to describe the evolution of the virus, its interaction with immune cells, importance of immune response and potential targets for drug development. The well-posedness of the model was determined based on positivity and boundedness of solutions. The model suggests that a greater efficacy of immune cells significantly reduces the viral load. Further, numerical simulation suggests that inhibiting the progression of latently infected cells to productively infected cells is paramount and this can be achieved by using viral transcriptase inhibitors. We suggest that these inhibitors together with the use of approved vaccines and re-purposed antiviral drugs such as Remdesivir and Baricitinib will have a great impact in controlling the severity of the virus in case of subsequent attacks. COVID-19 vaccines confer immunity by primarily utilising the SARS CoV-2 spike proteins. We evaluated the impact of immunization on target and infected cells. Results obtained from the simulations indicate that a lower vaccine efficacy requires booster shots to augment circulating antibodies necessary to nullify the virus. This model of in-host SARS CoV-2 dynamics has therefore provided knowledge useful to encourage the development of antiviral drugs focused on inhibiting transcription hence arresting viral replication.