SARS-CoV-2 and the Angiotensin-Converting Enzyme 2 Receptor: Angiotensin-Converting Enzyme Inhibitor/Angiotensin 2 Receptor Blocker Utilization and a Shift Towards the Renin-Angiotensin-Aldosterone System Classical Pathway

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus responsible for the coronavirus disease 2019 (COVID-19) pandemic, uses the surface angiotensin-converting enzyme 2 (ACE2) receptor as the site of entry into host cardiac, respiratory, intestinal, renal, and nervous system cells. Predisposing risk factors such as cardiovascular disease increase the risk of developing severe disease. Hypertension is characterized by the stimulation of the renin-angiotensin-aldosterone system (RAAS). Angiotensin-converting enzyme inhibitors (ACEis) and angiotensin 2 receptor blockers (ARBs), medications used to treat hypertension, inhibit RAAS and its downstream effects; however, they have also been shown to upregulate ACE2 receptors. In this review, we aim to evaluate the effectiveness of ACEi/ARBs as an adjunct therapy in patients with SARS-CoV-2 as well as examine the possible protective effects and impact on infection rate and disease severity. A PubMed literature search excluding sources outside the United States and duplicates was performed using the following search criteria: "COVID-19 AND cardiovascular disease AND ACEi AND ARB", "SARS-COVID-19 OR COVID-19, AND ACEi AND ARB AND Infection rate", "COVID-19 AND ACEi and ARB", "Omicron BA.1 and BA.2 AND ACE2 OR ARBs", "Omicron AND ACEi AND ARBs". This resulted in 33 final sources. The review concluded that ACEi/ARB therapy may continue to improve COVID-19 survival as previous treatment is associated with positive clinical outcomes. Patients taking ACEis or ARBs were found to have a decreased risk of hospitalization, reduced severity of COVID-19 pneumonia, a lesser need for mechanical ventilation, and an overall reduction in mortality rate. No statistically significant association between ACEi/ARB use and enhanced COVID-19 infectivity was found. The Omicron variant is theoretically more infectious and was associated with increased negative clinical outcomes in those undertreated with ACEis/ARBs. The majority of the literature supports the current guidelines from the American College of Cardiology (ACC), American Heart Association (AHA), European Society of Cardiology (ESC), and Heart Failure Society of America (HFSA), which state that ACEi and ARB medications should not be withdrawn from or initiated on patients with cardiovascular disease who are infected with SARS-CoV-2. More research needs to be conducted on the association between the emerging COVID-19 variants and ACEis/ARBs to give clinicians con