Relationship between ACE-inhibitors, ARBs and SARS-CoV-2 infection: where are we?

SARS-CoV-2 is spreading rapidly all over the world. The case fatality rate seems higher in cardiovascular disease and hypertension. Other comorbidities do not seem to confer the same risk, therefore the understanding of the relationship between infection and cardiovascular system could be a crucial point for the fight against the virus. A great interest is currently directed towards the angiotensin 2 converting enzyme (ACE 2) which is the SARS-CoV-2 receptor and creates important connections between the virus replication pathway, the cardiovascular system and blood pressure. All cardiovascular conditions share an imbalance of the renin angiotensin system (RAAS) in which ACE 2 plays a central role. In the last few days, much confusion has appeared about the management of therapy with angiotensin converting enzyme inhibitors (ACE-i) and angiotensin receptor blockers (ARBs) in infected patients and in those at risk of critical illness in case of infection. In this article we will try to reorder the major opinions currently emerging on this topic.

[1]  Michael Roth,et al.  Are patients with hypertension and diabetes mellitus at increased risk for COVID-19 infection? , 2020, The Lancet Respiratory Medicine.

[2]  D. Gurwitz.  Angiotensin receptor blockers as tentative SARS‐CoV‐2 therapeutics , 2020, Drug development research.

[3]  Shengqing Wan,et al.  Comparative genetic analysis of the novel coronavirus (2019-nCoV/SARS-CoV-2) receptor ACE2 in different populations , 2020, Cell Discovery.

[4]  Andrea Marzi,et al.  Functional assessment of cell entry and receptor usage for SARS-CoV-2 and other lineage B betacoronaviruses , 2020, Nature Microbiology.

[5]  G. Su,et al.  [Inhibitors of RAS Might Be a Good Choice for the Therapy of COVID-19 Pneumonia]. , 2020, Zhonghua jie he he hu xi za zhi = Zhonghua jiehe he huxi zazhi = Chinese journal of tuberculosis and respiratory diseases.

[6]  G. Cai.  Tobacco-Use Disparity in Gene Expression of ACE2, the Receptor of 2019-nCov , 2020 .

[7]  I. Kickbusch,et al.  Response to the emerging novel coronavirus outbreak , 2020, BMJ.

[8]  W. Zuo,et al.  Single-cell RNA expression profiling of ACE2, the putative receptor of Wuhan 2019-nCov , 2020, bioRxiv.

[9]  L. Sakr,et al.  Angiotensin converting enzyme inhibitors and risk of lung cancer: population based cohort study , 2018, British Medical Journal.

[10]  S. Bangalore,et al.  Angiotensin-Converting Enzyme Inhibitors in Hypertension: To Use or Not to Use? , 2018, Journal of the American College of Cardiology.

[11]  X. Li,et al.  The vasoprotective axes of the renin‐angiotensin system: Physiological relevance and therapeutic implications in cardiovascular, hypertensive and kidney diseases , 2017, Pharmacological research.

[12]  O. Jahn,et al.  TMPRSS2 and ADAM17 Cleave ACE2 Differentially and Only Proteolysis by TMPRSS2 Augments Entry Driven by the Severe Acute Respiratory Syndrome Coronavirus Spike Protein , 2013, Journal of Virology.

[13]  S. Harrap,et al.  The ACE2 gene: its potential as a functional candidate for cardiovascular disease. , 2013, Clinical science.

[14]  K. Pyrć,et al.  Replication-dependent downregulation of cellular angiotensin-converting enzyme 2 protein expression by human coronavirus NL63. , 2012, The Journal of general virology.

[15]  C. Disteche,et al.  Genes that escape from X inactivation , 2011, Human Genetics.

[16]  D. Tregouet,et al.  A polymorphism in ACE2 is associated with a lower risk for fatal cardiovascular events in females: the MORGAM project , 2011, Journal of the renin-angiotensin-aldosterone system : JRAAS.

[17]  J. Penninger,et al.  Angiotensin-converting enzyme 2 (ACE2) in disease pathogenesis. , 2010, Circulation journal : official journal of the Japanese Circulation Society.

[18]  D. Gu,et al.  Association study of ACE2 (angiotensin I-converting enzyme 2) gene polymorphisms with coronary heart disease and myocardial infarction in a Chinese Han population. , 2006, Clinical science.

[19]  S. Perlman,et al.  ACE2 Receptor Expression and Severe Acute Respiratory Syndrome Coronavirus Infection Depend on Differentiation of Human Airway Epithelia , 2005, Journal of Virology.

[20]  F. Frézard,et al.  Angiotensin-(1-7): blood, heart, and blood vessels. , 2005, Current medicinal chemistry. Cardiovascular and hematological agents.

[21]  Mark Chappell,et al.  A crucial role of angiotensin converting enzyme 2 (ACE2) in SARS coronavirus–induced lung injury , 2005, Nature Medicine.

[22]  Arthur S Slutsky,et al.  Angiotensin-converting enzyme 2 protects from severe acute lung failure , 2005, Nature.

[23]  D. Diz,et al.  Effect of Angiotensin-Converting Enzyme Inhibition and Angiotensin II Receptor Blockers on Cardiac Angiotensin-Converting Enzyme 2 , 2005, Circulation.

[24]  Chengsheng Zhang,et al.  Receptor and viral determinants of SARS-coronavirus adaptation to human ACE2 , 2005, The EMBO journal.

[25]  D. Moskowitz,et al.  The central role of angiotensin I-converting enzyme in vertebrate pathophysiology. , 2004, Current topics in medicinal chemistry.

[26]  G. Navis,et al.  Tissue distribution of ACE2 protein, the functional receptor for SARS coronavirus. A first step in understanding SARS pathogenesis , 2004, The Journal of pathology.

[27]  Nigel M Hooper,et al.  ACE2: from vasopeptidase to SARS virus receptor , 2004, Trends in Pharmacological Sciences.

[28]  R. Ardaillou.  Angiotensin II receptors. , 1999, Journal of the American Society of Nephrology : JASN.