Background: The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused the coronavirus disease 2019 (COVID-19), which is associated with cardiovascular problems and serious lung damage. COVID-19 patients with comorbid conditions are at a significantly elevated risk of increased morbidity and mortality. Angiotensin-converting enzyme 2 (ACE2) and transmembrane protease serine 2 (TMPRSS2) are the two key host contributing factors for the severity and pathogenesis of COVID-19. The principal SARS-CoV-2 entrance receptor, ACE2, is expressed equally in most organs and produces cardio-protective vasodilators by physically degrading angiotensin II, the main controller of the Renin-Angiotensin Aldosterone System. However, treatment for cardiovascular disease (CVD) commonly involves RAAS inhibitors, which may increase ACE2 expression. Objective: To summarize the pharmacological molecular discoveries into the processes of viral infection and its consequences for cardiovascular disease and to offer suggestions for the practical management and treatment of COVID-19-related cardiovascular injury. Methods: This review focuses on the important considerations related to the cardiovascular manifestations of COVID-19 and discusses the various mechanisms of COVID-19 that contribute to its molecular and pharmacological presentation of cardiovascular injury. Results: The host-pathogen relationship began with ACE2’s attachment to the S-protein and proceeded with TMPRSS2’s proteolytic cleavage of the viral spike (S)-protein and ACE2. Currently discovered protein-protein interactions explain the uniqueness of SARS-CoV-2 infection. Conclusion: COVID-19 is associated with cardiovascular problems and serious lung damage. ACE2 and TMPRSS2 are key host contributing factors for the severity and pathogenesis of COVID-19. The molecular discoveries into the processes of viral infection and its consequences for cardiovascular disease provide important considerations for the management and treatment of COVID-19-related cardiovascular injury.