Abstract
The COVID-19 pandemic has underscored the importance of understanding the interplay between the cardiovascular and immune systems during viral infections. SARS-CoV-2 enters human cells via the ACE-2 enzyme, initiating a cascade of immune responses. This study presents a coupled mathematical model that integrates the cardiovascular system (CVS) and immune system (IS), capturing their complex interactions during infection. The CVS model, based on ordinary differential equations, describes heart dynamics and pulmonary and systemic circulation, while the IS model simulates immune responses to SARS-CoV-2, including immune cell interactions and cytokine production. A coupling strategy transfers information from the IS to the CVS at specific intervals, enabling the exploration of immune-driven cardiovascular effects. Numerical simulations examined how these interactions influence infection severity and recovery. The coupled model accurately replicated the evolution of cardiac function in survivors and non-survivors of COVID-19. Survivors exhibited a left ventricular ejection fraction (LVEF) reduction of up to 25% while remaining within normal limits, whereas non-survivors showed a severe 4-fold decline, indicative of myocardial dysfunction. Similarly, the right ventricular ejection fraction (RV EF) decreased by approximately 50% in survivors but underwent a drastic 5-fold reduction in non-survivors. These findings highlight the model's capacity to distinguish differential cardiac dysfunction across clinical outcomes and its potential to enhance our understanding of COVID-19 pathophysiology.