Integrative Modeling of SARS-CoV-2 Infection Dynamics to Inform COVID-19 Vaccination Strategies

Abstract Non-pharmaceutical interventions were very instrumental in the early phases of COVID-19 pandemic. Fortunately, the urgency to control the crisis prompted an accelerated vaccine development process, saving millions of lives globally. Despite these measures, cases of COVID-19 and other variants SARS-CoV-2 are still being reported in different countries and regions. We present a within-host mathematical model of SARS-CoV-2 infection that incorporates target cell dynamics, innate and adaptive immune responses, and vaccine interventions. Analytical results identify the basic reproduction number, R 0 , as the threshold for infection persistence. Simulations show that immune responses, both lytic and non-lytic, are critical in controlling viral replication, with vaccine-induced immunity further reducing viral load and protecting epithelial cells. Immune-boosting strategies and monoclonal antibody therapies targeting intracellular replication outperform entry-blocking interventions alone, while combination approaches yield the greatest reduction in peak viral load and fastest clearance. Timing is crucial: early vaccination or treatment maximizes benefits, whereas delays allow higher viral titers to persist. These results underscore the importance of early, multi-mechanism interventions, particularly for vulnerable populations such as the elderly and immunocompromised. The model offers a framework for evaluating treatment strategies and can be extended to incorporate pharmacokinetics/pharmacodynamics or patient-specific calibration for improved predictive accuracy.