Coronavirus and ACE2: What is the evidence regarding ACEis and ARBs?

March 16, 2020

Published March 16, 2020


The current pandemic associated with the SARS-CoV-2 virus and COVID-19 disease is unprecedented and catastrophic.

As concerned physicians and scientists working in this area, we summarize the evidence on the NephJC website, The Coronavirus Conundrum: ACE2 and Hypertension Edition, (which will be updated in real time) and call for greater understanding and systematic data gathering, rather than hasty decision-making based upon incomplete or inaccurate information, or unjustified extrapolations.

Emerging preliminary reports from China suggest hypertension may be a potential risk for severity of COVID-19. However, these studies do not adjust for confounders, such as age and comorbid disease. Recently, peer-reviewed journals (such as The British Medical Journal and Lancet Respiratory Medicine) and the lay press have circulated provocative letters and articles calling for physicians to stop angiotensin converting enzyme inhibitors (ACEis) and/or angiotensin receptor blockers (ARBs) for fear that these agents could upregulate ACE2 and, thereby enhance cellular entry of SARS-CoV-2. Because the SARS-CoV-2 virus utilizes components of the renin angiotensin system (RAS) (ACE2 and TMPRSS2) to enter cells, it seemed plausible that ACEis and ARBs might exacerbate or even mitigate COVID-19.

Reports and analyses on this topic are emerging rapidly. We have reviewed all available evidence (pre-clinical and clinical) whether these drugs have benefit or harm in COVID-19.

For now, we see no reason to presumptively stop ACEis or ARBs.

For patients with confirmed COVID-19 and who are receiving ACEi/ARB agents, decisions on continuing or stopping these drugs should be done on an individualized basis by the treating physician.



Several organizations (American College of Physicians, the European Society of Cardiology, Hypertension Canada, the Canadian Cardiovascular Society, UK Renal Association, and the International Society of Hypertension, among others) have released statements corroborating this approach.

The current scientific and clinical questions include: 

  • Is there a link between viral infection and hypertension in humans?
  • Are patients on ACEis at increased/decreased risk of infection or severity of disease? 
  • Are patients on ARBs at increased/decreased risk of infection or severity of disease? 
  • Does modulation of these drugs (starting, stopping, or continuing) lead to better or worse outcomes in COVID-19?


Our purpose is to continuously appraise the literature and make informed decisions to help our patients and colleagues. We will continue to provide updates about this issue on the NephJC website.

We invite all of the nephrology community to contribute to the conversation on this important topic. Please contact anyone on the NephJC COVID-19 and ACE2 in Cardiovascular, Lung, and Kidney Working Group with suggestions. If you would like to join the work group, we would welcome this.

 

NephJC Working Group

Daniel Batlle, MD, Northwestern University

Vivek Bhalla, MD, Stanford University

Louise M Burrell, MD, University Melbourne, Australia

James Brian Byrd, MD, MS, University of Michigan

Jordana Cohen, MD, MSCE, University of Pennsylvania

Swapnil Hiremath, MD, MPH, University of Ottawa

Matt Luther, MD, Vanderbilt University

Michelle Rheault, MD, University of Minnesota

María José Soler, MD, PhD, Hospital del Vall d’Hebron. Barcelona, Spain

Andrew South, MD, MS, Wake Forest School of Medicine, Brenner Children’s Hospital

Matthew A. Sparks, MD, FASN Duke University

Laurie Tomlinson, MD, London School of Hygiene & Tropical Medicine, UK

Paul Welling, MD, Johns Hopkins University

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Published March 16, 2020


The current pandemic associated with the SARS-CoV-2 virus and COVID-19 disease is unprecedented and catastrophic.

As concerned physicians and scientists working in this area, we summarize the evidence on the NephJC website, The Coronavirus Conundrum: ACE2 and Hypertension Edition, (which will be updated in real time) and call for greater understanding and systematic data gathering, rather than hasty decision-making based upon incomplete or inaccurate information, or unjustified extrapolations.

Emerging preliminary reports from China suggest hypertension may be a potential risk for severity of COVID-19. However, these studies do not adjust for confounders, such as age and comorbid disease. Recently, peer-reviewed journals (such as The British Medical Journal and Lancet Respiratory Medicine) and the lay press have circulated provocative letters and articles calling for physicians to stop angiotensin converting enzyme inhibitors (ACEis) and/or angiotensin receptor blockers (ARBs) for fear that these agents could upregulate ACE2 and, thereby enhance cellular entry of SARS-CoV-2. Because the SARS-CoV-2 virus utilizes components of the renin angiotensin system (RAS) (ACE2 and TMPRSS2) to enter cells, it seemed plausible that ACEis and ARBs might exacerbate or even mitigate COVID-19.

Reports and analyses on this topic are emerging rapidly. We have reviewed all available evidence (pre-clinical and clinical) whether these drugs have benefit or harm in COVID-19.

For now, we see no reason to presumptively stop ACEis or ARBs.

For patients with confirmed COVID-19 and who are receiving ACEi/ARB agents, decisions on continuing or stopping these drugs should be done on an individualized basis by the treating physician.



Several organizations (American College of Physicians, the European Society of Cardiology, Hypertension Canada, the Canadian Cardiovascular Society, UK Renal Association, and the International Society of Hypertension, among others) have released statements corroborating this approach.

The current scientific and clinical questions include: 

  • Is there a link between viral infection and hypertension in humans?
  • Are patients on ACEis at increased/decreased risk of infection or severity of disease? 
  • Are patients on ARBs at increased/decreased risk of infection or severity of disease? 
  • Does modulation of these drugs (starting, stopping, or continuing) lead to better or worse outcomes in COVID-19?


Our purpose is to continuously appraise the literature and make informed decisions to help our patients and colleagues. We will continue to provide updates about this issue on the NephJC website.

We invite all of the nephrology community to contribute to the conversation on this important topic. Please contact anyone on the NephJC COVID-19 and ACE2 in Cardiovascular, Lung, and Kidney Working Group with suggestions. If you would like to join the work group, we would welcome this.

 

NephJC Working Group

Daniel Batlle, MD, Northwestern University

Vivek Bhalla, MD, Stanford University

Louise M Burrell, MD, University Melbourne, Australia

James Brian Byrd, MD, MS, University of Michigan

Jordana Cohen, MD, MSCE, University of Pennsylvania

Swapnil Hiremath, MD, MPH, University of Ottawa

Matt Luther, MD, Vanderbilt University

Michelle Rheault, MD, University of Minnesota

María José Soler, MD, PhD, Hospital del Vall d’Hebron. Barcelona, Spain

Andrew South, MD, MS, Wake Forest School of Medicine, Brenner Children’s Hospital

Matthew A. Sparks, MD, FASN Duke University

Laurie Tomlinson, MD, London School of Hygiene & Tropical Medicine, UK

Paul Welling, MD, Johns Hopkins University

Date:
Monday, March 16, 2020