Angiotensin Converting Enzyme (ACE2) is a known binding site for Coronavirus 2019 (COVID-19). Angiotensin Converting Enzyme Inhibitors (ACEIs) and Angiotensin Receptor Blockers (ARBs) work to decrease the ability of (ACE2) to function properly. It is hypothesized by researchers that the blockage of (ACE2) will lead the body to increase expression of the gene to produce more (ACE2). This could potentially bring about an overall increase in the potential binding sites available for COVID-19. This study reviews (ACE2) expression in animal and human subjects using direct and indirect methods of protein analysis. The animal models provide no conclusive data and the human data heavily implies that administration of ACEIs/ARBs do not increase ACE2 protein expression. Based upon past evidence and the findings of this study the researchers conclude that ACEIs and ARBs offer no additional risk of complications from COVID-19 infection.
Introduction and Methods
The data regarding ACE2 expression in the presence of inhibitors is largely mixed. Data from animal models was nonspecific and there was limited human data. This study reviews literature studying the expression of ACE2 with inhibitors in order toacquire a more complete understanding of the data available. The researchers searched Google scholars and Pubmed for all available literature. No restrictions were imposed on the search for literature and all data acquired was manually curated to affirm validity.
The animal model studies did not provide consistent evidence for any conclusion. Several studies showed an increase in ACE2 expression while others showed none. The results were generally unreliable and showed no real trend. The lack of consistency could be due to a lack of proper analysis to ascertain a proper therapeutic dose. Therefore, the researchers did not know the best dose for any particular animal model. These values were adjusted to be used in a 60kg human, which resulted in a dose that is higher than what is considered safe for human use. Because the animal studies fail to have a recommended dose they have little to no meaning when their data is applied to a human model. The human model studies had mixed results like the animal model. However, when looking at the bulk of the data available from these studies it strongly implies that there is no association between ACE2 expression levels in a human body and the use of ARBs or ACEIs.
In order for the hypothesis to be supported, several experimental findings would need to be observed. 1) ACE2 expression would need to be observed to increase in animal models. This claim is largely unsupported by the data in this study. 2) Tissues with low expression of ACE2 would have an increase in expression in the presence of ARBs/ACEIs. There is no available evidence supporting this claim either. 3) An increase in ACE2 via ARBs/ACEIs leads to increased COVID-19 cell infection. SARS-CoV-2 has an incredibly high affinity for ACE2. However, ACE2 expression decreases with age yet the elderly tend to have more severe symptoms. It is largely unclear weather changes in ACE2 could lead to increased infection. 4) Human studies would need to find a significant difference in expression in reference to ARBs/ACEIs versus if there were none present. There are studies that support this claim, however no data from these studies is statistically significant and is modest support at best. 5) Data showing patients with COVID-19 that take ARBs/ACEIs have higher morbidity and mortality rates that are dose dependent. Studies actually show the opposite effect on morbidity and mortality. Patients taking ARBs/ACEIs actually have a lower morbidity rate and mortality which contradicts the hypothesis. Therefore, based upon the data found the researchers concluded that patients should continue their use of ARBs/ACEIs as recommended by health associations and other publications.