Use of Angiotensin-Converting Enzyme Inhibitors and Angiotensin II Receptor Blockers During the COVID-19 Pandemic: A Modeling Analysis

Angiotensin-converting enzyme inhibitors (ACEi) and angiotensin II receptor blockers (ARB) are frequently prescribed for a range of diseases including hypertension, proteinuric chronic kidney disease, and heart failure. There is evidence indicating that these drugs upregulate ACE2, a key component of the renin-angiotensin system (RAS) and is found on the cells of a number of tissues, including the epithelial cells in the lungs. While ACE2 has a beneficial role in many diseases such as hypertension, diabetes, and cardiovascular disease, it also serves as a receptor for both SARS-CoV and SARS-CoV-2 via binding with the spike protein of the virus, thereby allowing it entry into host cells. Thus, it has been suggested that these therapies can theoretically increase the risk of SARS- CoV-2 infection and cause more severe COVID-19. Given the success of ACEi and ARBs in cardiovascular diseases, we seek to gain insights into the implications of these medications in the pathogenesis of COVID-19. To that end, we have developed a mathematical model that represents the RAS, binding of ACE2 with SARS-CoV-2 and the subsequent cell entry, and the host’s acute inflammatory response. The model can simulate different levels of SARS-CoV-2 exposure, and represent the effect of commonly prescribed anti-hypertensive medications, ACEi and ARB, and predict tissue damage. Model simulations indicate that whether the extent of tissue damage may be exacerbated by ACEi or ARB treatment depends on a number of factors, including the level of existing inflammation, dosage, and the effect of the drugs on ACE2 protein abundance. The findings of this study can serve as the first step in the development of appropriate and more comprehensive guidelines for the prescription of ACEi and ARB in the current and future coronavirus pandemics.