Patients Taking ACE Inhibitors or ARBs: Higher COVID-19 Risk but Milder Symptoms? Here’s What the Research Says
If you or a loved one takes ACE inhibitors (like lisinopril) or ARBs (like losartan) for high blood pressure, heart failure, or kidney disease, you’ve probably wondered: Could these common medications affect COVID-19 risk or how severe your symptoms get? It’s a question that’s haunted millions of patients—and one that researchers from Wuhan University, the University of Oklahoma Health Sciences Center, and Xinjiang Medical University set out to explore in a 2020 Chinese Medical Journal editorial. Their conclusion? We have more questions than answers—but the evidence we do have offers critical nuance.
First, a Quick Refresher: ACEIs, ARBs, and ACE2
ACE inhibitors (ACEIs) and angiotensin II receptor blockers (ARBs) are cornerstone treatments for hypertension, heart failure, and diabetic kidney disease. They work by targeting the renin-angiotensin-aldosterone system (RAAS), a pathway that regulates blood pressure and fluid balance. But here’s the pandemic twist: The same pathway includes ACE2—a protein that acts as the doorway for SARS-CoV-2 (the virus that causes COVID-19) to enter human cells.
The ACE2 Dilemma: Risk vs. Protection
SARS-CoV-2 uses membrane-bound ACE2 (the version on cell surfaces) to slip into cells. Early in the pandemic, some researchers worried ACEIs/ARBs might increase membrane-bound ACE2, giving the virus more “doors” to use. But ACE2 isn’t a one-trick pony—it comes in two forms:
- Membrane-bound ACE2: The “doorway” the virus uses to infect cells.
- Soluble ACE2: A free-floating version that might block the virus by competing for binding to membrane-bound ACE2.
If ACEIs/ARBs boost membrane-bound ACE2, infection risk could rise. But if they increase soluble ACE2, they might offer protection. The problem? Most animal studies (which used far higher drug doses than humans take) showed increased membrane-bound ACE2—but we have no direct evidence of how these drugs affect ACE2 forms in people. Animal results don’t always translate to humans, and we’re missing key data on human tissue ACE2 levels.
Could ACEIs/ARBs Reduce COVID-19 Severity?
While the infection risk question is murky, there’s a more promising angle: ACE2 protects against lung injury. When SARS-CoV-2 binds to ACE2, it degrades the protein. Less ACE2 means more angiotensin II—a molecule that fuels inflammation and lung damage (seen in SARS and H5N1 flu studies). ACEIs and ARBs help here:
- ACEIs block angiotensin II production.
- ARBs stop angiotensin II from attaching to cells.
Both actions reduce inflammation and lung injury—potentially making COVID-19 symptoms milder. The researchers behind the Chinese Medical Journal editorial hypothesize this could explain why some ACEI/ARB users have better outcomes.
What Do Human Studies Show?
Two large, high-quality studies shed light on real-world outcomes:
- Zhang et al. (2020, Circulation Research): Among hospitalized COVID-19 patients with hypertension, those using ACEIs/ARBs had lower all-cause mortality than non-users—even when blood pressure was similar between groups. This suggests the benefit wasn’t just from better blood pressure control; ACEIs/ARBs might directly reduce COVID-19 severity.
- Reynolds et al. (2020, New England Journal of Medicine): Using propensity score matching (a method to balance user and non-user groups by accounting for factors like age, health conditions, and medication use), the study found no significant difference in COVID-19 infection risk or severity between ACEI/ARB users and non-users.
Genetics Matter Too
ACE2 gene variations (called polymorphisms) affect how the protein works. For example:
- Some variations make ACE2 more “sticky” for SARS-CoV-2, increasing infection risk.
- Others make ACE2 less effective at protecting the lungs, worsening symptoms.
These genetic differences could explain why study results sometimes conflict—ACEI/ARB effects might depend on a person’s unique ACE2 profile.
Expert Advice: Don’t Stop Your Meds
Major medical groups like the European Society of Cardiology (ESC) and American Heart Association (AHA) have consistently advised patients to keep taking ACEIs/ARBs unless their doctor tells them otherwise. Why?
- There’s no strong evidence these drugs increase COVID-19 risk.
- Stopping them could worsen heart or kidney health—risks that are far more certain than any unproven COVID-19 concerns.
The Bottom Line
We still don’t have all the answers about ACEIs/ARBs and COVID-19. We need large, well-designed human trials to understand:
- How these drugs affect ACE2 forms in people.
- Whether they increase infection risk or reduce severity.
- How genetics interact with drug effects.
For now, the best advice is simple: Follow your doctor’s guidance. If you have questions about your medications, don’t stop them cold—talk to your healthcare provider first.
The original editorial was published in the Chinese Medical Journal in 2020 by Jie-Lin Deng (Department of Cardiology, Renmin Hospital of Wuhan University; Department of Medicine, University of Oklahoma Health Sciences Center), Yun-Qiu Jiang (Department of Medicine, University of Oklahoma Health Sciences Center), Yan-Kai Guo (Department of Cardiology, Renmin Hospital of Wuhan University; Cardiac Pacing and Electrophysiology Department, The First Affiliated Hospital of Xinjiang Medical University), and Hong-Liang Li (Department of Medicine, University of Oklahoma Health Sciences Center).
doi.org/10.1097/CM9.0000000000000996
doi.org/10.1016/S2213-2600(20)30116-8
doi.org/10.1128/JVI.00127-20
doi.org/10.1161/01.HYP.0000124667.34652.1a
doi.org/10.3109/10715762.2012.684878
doi.org/10.1161/CIRCULATIONAHA.104.510461
doi.org/10.1038/s41586-020-2012-7
doi.org/10.1007/s00134-020-05985-9
doi.org/10.1038/nm1267
doi.org/10.1038/nature03712
doi.org/10.1038/ncomms4594
doi.org/10.1161/01.hyp.31.2.699
doi.org/10.1161/ATVBAHA.117.310499
doi.org/10.1016/s0008-6363(00)00044-4
doi.org/10.1161/01.hyp.23.2.258
doi.org/10.1161/CIRCRESAHA.120.317134
doi.org/10.1056/NEJMoa2008975
doi.org/10.1164/rccm.2108086
doi.org/10.1101/2020.04.07.024752
doi.org/10.1097/01.CCM.0000206107.92476.39
Was this helpful?
0 / 0