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, R0, 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. Competing Interest Statement The authors have declared no competing interest. Funding Statement This study did not receive any funding Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes Data Availability All data produced in the present work are contained in the manuscript