Inhibitors of the Renin-Angiotensin-Aldosterone pathway (ie. ACE inhibitors, angiotensin-receptor blockers) are commonly used to treat hypertension. Previous animal studies, which have shown that these inhibitors can increase the level of ACE2 expression in one's body, coupled with the cardiovascular comorbidities, lead to speculation amongst clinicians and researchers that these widely-used drugs may be harmful for patients with COVID-19. Current studies (June 2020) have shown no evidence of harm with continued use of RAAS inhibitors in COVID-19 patients. 

- database study involving 8910 patients from 11 countries
- case control study in the Lombardy region of Italy
- study based on data from the electronic health records in the New York University Langone Health system


Inhibitors of the Renin–Angiotensin–Aldosterone System (RAAS) and COVID-19

Vitamin D is a nutrient that is both endogenously synthesized in the skin and consumed dietarily.  Its biologically active form [1,25-(OH)2D] is a known negative regulator of the Renin-Angiotensin System (RAS).  1,25-(OH)2D has been shown to increase ACE2 expression and suppress the inflammatory outcomes caused by angiotensin II (Ang II).  Additionally, vitamin D can modulate the immune system by inhibiting B-cell and T-cell proliferation as well as inducing T-regulatory cells, which suppress pro-inflammatory cytokines and increase anti-inflammatory cytokines.  These processes may make vitamin D a useful molecule in treating or preventing a SARS-CoV-2 infection.

Using Vitamin D to Mitigate COVID-19

Michigan State University

The renin–angiotensin system (RAS) plays a central role in cardiovascular physiology by maintaining blood pressure, controlling blood volume, regulating sodium concentration in the plasma, and keeping the electrolytes balanced.  When homeostasis is perturbed, the RAS can cause inflammation and structural remodeling of the tissue.  This can lead to vascular, renal, and cardiac damage.

Renin–Angiotensin System (RAS)

Physiological Components of the RAS

Ang II is a hormone that is regulated by the RAS.  The excessive adipose tissue associated with obesity is known to secrete this molecule which stimulates inflammation, insulin resistance, oxidative stress, and vasoconstriction.  Insulin resistance can exacerbate these conditions by further stimulating the RAS.  A relationship exists between pancreatic beta islet cells (B-cells) and the RAS: B-cell dysfunction leads to increased expression AT1R, the receptor for Ang II, and insulin resistance while RAS inhibition increases B-cell function and insulin sensitivity.  

Renin-Angiotensin System (RAS) Activity May Contribute to COVID-19 Morbidity and Mortality in Obese Patients

The renin-angiotensin system (RAS) is also referred as the renin-angiotensin-aldosterone system (RAAS) due to the role of the hormone aldosterone within this system. Aldosterone is released from the adrenal cortex when angiotensin is formed. As a result, this hormone can interrupt the homeostasis of this endocrine system. 

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