The Latest on Using ACE inhibitors and ARBs to Improve COVID-19 Outcomes

April 29, 2020

There is still discussion and confusion about ACE inhibitors and ARBs. What is the story behind this, and what do we actually know?

Both ACEI and ARBs block the Renin-Angiotensin System (RAAS), albeit by different mechanisms. The back and forth in the medical community exists, due to there being opposing advantages/disadvantages for the changes that occur with RAAS manipulation. Despite there still being uncertainty about whether pharmaceutical blockade of RAAS results in a positive or negative (or possibly no change) impact on COVID-19 infection, more expert voices giving commentary in the literature appear to believe the answer will ultimately be that ACEI and ARBs will improve outcomes.

That being said, there is far from enough information at this point to be declarative in advice either way. Many major organizations that have weighed in have recommended that no change to ACEI or ARB treatment for patients be made at this time. This seems by far the most prudent course of action with our current knowledge base.

  • COVID-19 enters cells by viral protein binding to ACE2.  Therefore, increased levels of ACE2 could increase viral entry.  
Image: 2020 The University of Tokyo
  • Other modes of cellular viral entry exist. 
  • ACE2 is downregulated after SARS viral entry which resulted in lung injury.
  • High levels of ACE2 have been associated with decreased inflammation which could prevent the “cytokine storm” associated with many severe COVID-19 infections.
  • Early examination of the association between ACEI/ARB use and COVID-19 outcomes have either not found an association, or found an advantage to their use ( preprint found an advantage, and a retrospective analysis also found an advantage).  Note - not a complete review of all literature.

Bottom line:  There is a theoretical advantage and disadvantage to blockade of the RAAS system in COVID-19 infections.  Currently, the available evidence appears to be leaning to an advantage for RAAS blockade, but it is still too early to say with certainty.  Therefore, it seems prudent to follow the advice of multiple organizations which recommend no change in the prescription of medications that cause RAAS blockade.