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Classical and Counter-Regulatory Renin-Angiotensin System: Potential Key Roles in COVID-19 Pathophysiology
Moudhi Almutlaq1,2, Abir Abdullah Alamro2, Fayhan Alroqi1,3,4
1King Abdullah International Medical Research Centre, King Abdulaziz Medical City, Ministry of National Guard Health Affairs, Riyadh, Saudi Arabia.
Abstract:
In the current COVID-19 pandemic, severe acute respiratory syndrome coronavirus 2 uses angiotensin-converting enzyme-2 (ACE-2) receptors for cell entry, leading to ACE-2 dysfunction and downregulation, which disturb the balance between the classical and counter-regulatory renin-angiotensin system (RAS) in favor of the classical RAS. RAS dysregulation is one of the major characteristics of several cardiovascular diseases; thus, adjustment of this system is the main therapeutic target. RAS inhibitors-particularly angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin II type 1 receptor blockers (ARBs)-are commonly used for treatment of hypertension and cardiovascular disease. Patients with cardiovascular diseases are the group most commonly seen among those with COVID-19 comorbidity. At the beginning of this pandemic, a dilemma occurred regarding the use of ACEIs and ARBs, potentially aggravating cardiovascular and pulmonary dysfunction in COVID-19 patients. Urgent clinical trials from different countries and hospitals reported that there is no association between RAS inhibitor treatment and COVID-19 infection or comorbidity complication. Nevertheless, the disturbance of the RAS that is associated with COVID-19 infection and the potential treatment targeting this area have yet to be resolved. In this review, the link between the dysregulation of classical RAS and counter-regulatory RAS activities in COVID-19 patients with cardiovascular metabolic diseases is investigated. In addition, the latest findings based on ACEI and ARB administration and ACE-2 availability in relation to COVID-19, which may provide a better understanding of the RAS contribution to COVID-19 pathology, are discussed, as they are of the utmost importance amid the current pandemic.
Insights
COVID-19 disrupts the renin-angiotensin system (RAS), impacting cardiovascular health. This review examines RAS dysregulation in COVID-19 patients and the role of RAS inhibitors, like ACE inhibitors and ARBs, in managing these conditions.
Area of Science:
- Cardiovascular Medicine
- Infectious Diseases
- Pharmacology
Background:
- Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) utilizes angiotensin-converting enzyme-2 (ACE-2) receptors for cell entry.
- SARS-CoV-2 infection leads to ACE-2 dysfunction and downregulation, disrupting the balance of the renin-angiotensin system (RAS).
- RAS dysregulation is a key feature of cardiovascular diseases, making its modulation a therapeutic target.
Purpose of the Study:
- To investigate the link between classical and counter-regulatory RAS dysregulation in COVID-19 patients with cardiovascular metabolic diseases.
- To discuss the latest findings on angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin II type 1 receptor blockers (ARBs) in relation to COVID-19.
- To understand the RAS contribution to COVID-19 pathology and explore potential therapeutic strategies.
Main Methods:
- Review of current literature on RAS, COVID-19, and cardiovascular comorbidities.
- Analysis of clinical trial data regarding the use of RAS inhibitors in COVID-19 patients.
- Investigation of the impact of ACE-2 availability and RAS inhibitor administration on COVID-19 outcomes.
Main Results:
- Early concerns about RAS inhibitors worsening COVID-19 outcomes were not supported by clinical trials.
- No association found between RAS inhibitor treatment and increased risk of COVID-19 infection or complications.
- COVID-19 infection significantly disturbs the RAS balance, favoring the classical pathway.
Conclusions:
- Understanding RAS dysregulation in COVID-19 is crucial for patient management.
- RAS inhibitors (ACEIs and ARBs) appear safe and potentially beneficial in COVID-19 patients with cardiovascular conditions.
- Further research is needed to fully elucidate the role of RAS in COVID-19 and optimize targeted therapies.
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