Renin-Angiotensin System Modulation in COVID-19 Management
Summary
The renin–angiotensin system (RAS) plays a central role in cardiovascular and pulmonary homeostasis by regulating vascular tone, fluid balance and inflammatory responses. In COVID-19, the causative virus binds to angiotensin-converting enzyme 2 (ACE2), leading to downregulation of this protective axis and a relative rise in angiotensin II levels. Elevated angiotensin II acting through the angiotensin II type 1 receptor (AT1R) promotes vasoconstriction, oxidative stress, endothelial dysfunction and pro-inflammatory signalling, all of which contribute to acute lung injury, thromboinflammation and multiorgan damage. Pharmacological modulation of RAS with angiotensin-converting enzyme inhibitors (ACEIs) or angiotensin receptor blockers (ARBs) may restore balance by attenuating angiotensin II–AT1R signalling and preserving the counter-regulatory ACE2–angiotensin(1-7)–Mas receptor pathway. Beyond established antihypertensive indications, RAS modulation has been investigated for preventing severe respiratory complications, mitigating renal and cardiovascular sequelae, and potentially reducing viral entry through recombinant soluble ACE2 decoys. Clinical trials and observational studies have sought to define the net effect of ACEIs/ARBs on COVID-19 susceptibility, disease progression and mortality, while emerging compounds such as bisartans aim to combine antiviral and anti-inflammatory properties. The global significance of this strategy lies in repurposing widely available drugs to improve outcomes and inform the management of future viral respiratory threats.
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Renin-Angiotensin System Modulation in COVID-19 Management publication trend
The graph below shows the total number of articles in renin-angiotensin system modulation in covid-19 management across all publications each year (not limited to Nature Index journals).
Technical terms
Renin–Angiotensin System (RAS): A hormone cascade that regulates blood pressure, fluid and electrolyte balance, and systemic vascular resistance.
Angiotensin-converting enzyme 2 (ACE2): A membrane-bound enzyme that degrades angiotensin II to angiotensin(1-7) and serves as the cellular receptor for SARS-CoV-2.
Angiotensin-converting enzyme inhibitors (ACEIs): Drugs that block conversion of angiotensin I to angiotensin II, reducing vasoconstriction and aldosterone release.
Angiotensin receptor blockers (ARBs): Agents that selectively antagonise the AT1R, inhibiting angiotensin II-mediated vasoconstrictive and pro-inflammatory effects.
Angiotensin II type 1 receptor (AT1R): A receptor mediating the classical actions of angiotensin II, including vasoconstriction, sodium retention and inflammatory cytokine release.
References
- Effects of Losartan on Patients Hospitalized for Acute COVID-19: A Randomized Controlled Trial. Clinical Infectious Diseases (2024).
- Impact of prior antihypertensive treatment on COVID-19 outcomes, by active ingredient. Inflammopharmacology (2024).
- Role of Angiotensin II in Cardiovascular Diseases: Introducing Bisartans as a Novel Therapy for Coronavirus 2019. Biomolecules (2023).
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