COVID-19, ACE2, and the cardiovascular consequences
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Key result
RAAS blockers and statins regulate ACE2 expression, requiring trials to assess COVID-19 severity in CVD.
Why the study?
Concerns emerged regarding whether patients with hypertension or CVD taking RAAS blockers or statins face higher SARS-CoV-2 infection risk, whether therapy should be stopped, and the viability of ACE2 blockade.
Does RAAS blockade alter ACE2 expression and affect COVID-19 severity in patients with cardiovascular disease?
Design
Perspective / review
Authors
Discussion
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Member takes
Implication
Does not justify discontinuing RAAS blockers or statins in CVD patients; leaves open effects on COVID-19 severity via ACE2, requiring trials.
Key Points
- To critically examine the mechanisms linking SARS-CoV-2 to ACE2, assess how RAAS blockers and statins regulate ACE2 expression, and evaluate whether targeting ACE2 is a safe and viable therapeutic approach in cardiovascular disease.
- Critical perspective and narrative synthesis evaluating molecular mechanisms of SARS-CoV-2 cellular entry via the membrane-bound ACE2 receptor.
- Review of preclinical and clinical evidence on the regulation of ACE2 by RAAS inhibitors (ACE inhibitors, AT1 receptor blockers, mineralocorticoid receptor antagonists) and statins in cardiovascular and pulmonary disease models.
- SARS-CoV-2 utilizes membrane-bound ACE2 for host cellular entry across multiple organs, including the lung, heart, kidney, brain, and gut.
- ACE2 confers intrinsic cardiovascular protection by metabolizing harmful ANG II into the counter-regulatory peptide Ang-(1-7).
- While RAAS inhibitors and statins upregulate ACE2 expression, existing evidence emphasizes the protective cardiovascular role of ACE2 and highlights the potential harm of discontinuing these essential therapies in patients with cardiovascular disease.
Structured PICO
Does RAAS blockade alter ACE2 expression and affect COVID-19 severity in patients with cardiovascular disease?
P
Population
Patients with underlying cardiovascular disease or hypertension, and experimental models
I
Intervention
RAAS blockade (ACE inhibitors, ARBs) and statins
This perspective highlights the theoretical risks and benefits of RAAS blockade in COVID-19 via ACE2 modulation, emphasizing the urgent need for clinical trials rather than preemptive discontinuation of these therapies.
Limitations
- Current clinical data on the ACE2-Ang-(1-7) pathway are quite limited relative to experimental data.
- Existing evidence often comes from smaller cross-sectional observational studies with incomplete RAAS measurements.
- Essentially no clinical data on how ACEIs or ARBs may impact the ACE2-Ang-(1-7) pathway in lung, heart or brain.
- Lack of clinical data on the effects of ACEIs and ARBs on human pulmonary disease and RAAS expression
- Incomplete RAAS measurements in existing observational studies
Cite This Study
South et al. (2020) conducted a review in COVID-19 and Cardiovascular Disease. RAAS blockers and statins was evaluated. RAAS blockers and statins regulate ACE2 expression, the coreceptor for SARS-CoV-2, necessitating urgent clinical trials to determine their impact on COVID-19 severity in patients with cardiovascular disease.
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