ACE2 and COVID-19: using antihypertensive medications and pharmacogenetic considerations.

Eric M Snyder,Bruce D Johnson

doi:10.2217/pgs-2020-0048

Abstract

COVID-19 utilizes the ACE2 pathway as a means of infection. Early data on COVID-19 suggest heterogeneity in the severity of symptoms during transmission and infection ranging from no symptoms to death. The source of this heterogeneity is likely multifaceted and may have a genetic component. Demographic and clinical comorbidities associated with the severity of infection suggest that possible variants known to influence the renin–angiotensin–aldosterone (RAAS) system pathway (particularly those that influence ACE2) may contribute to the heterogenous infection response. ACE2 and Ang(1–7) (the product of ACE2) seem to have a protective effect on the pulmonary and cardiac systems. Hypertension medication modulation, may alter ACE2 and Ang(1–7), particularly in variants that have been shown to influence RAAS system function, which could be clinically useful in patients with COVID-19.

Highlights

While it is likely that a portion of the differences in COVID-19 infection rates and severity are influenced by environment or traditional demographic variables known to influence ACE2 levels, the known heterogeneity of this infection may have genetic associations
Along with hypertension and diabetes being common comorbidities for COVID-19, older individuals and males are more susceptible to the infection, both of which are associated with differences in ACE2 expression and activity
There is strong evidence that decreased ACE2 and Ang(1–7) levels are associated with poor prognosis in patients with respiratory dysfunction, including acute lung injury (ALI) and acute respiratory distress syndrome (ARDS)

Summary

MAS receptor Protective

In addition to hypertension and diabetes being common comorbidities for COVID-19, older individuals and males are more susceptible to the infection (and have demonstrated more severe cardiopulmonary complications from coronavirus), both of which are associated with differences in ACE2 levels. Previous work has demonstrated that the administration of an ACE-inhibitor or an ARB causes an increase in Ang(1–7) levels [34] Both ACE-inhibition and ARB administration increase the activity, and expression, of ACE2, which may be differential based on variants of ACE and Ang-II that have previously been shown to alter enzyme and receptor function, respectively [34]. Given this complex interaction along a pathway that is commonly treated with antihypertensive medications, it is possible that pharmacotherapy can target this pathway in established ways to attenuate ACE2 levels and reduce the likelihood for infections from COVID-19 and that augmentation of this same pathway, increasing ACE2 and Ang(1–7) may be beneficial, post infection. These considerations may be impactful when considering genetic variants along this same pathway that have previously demonstrated meaningful functionality in humans

Conclusion

Executive summary