Potential harmful effects of discontinuing ACE-inhibitors and ARBs in COVID-19 patients

  1. Gian Paolo Rossi  Is a corresponding author
  2. Viola Sanga  Is a corresponding author
  3. Matthias Barton  Is a corresponding author
  1. University of Padova, Italy
  2. University of Zurich, Switzerland

Abstract

The discovery that SARS-CoV-2 (Severe Acute Respiratory Syndrome Coronavirus 2) RNA binds to the angiotensin converting enzyme (ACE)-2, which is highly expressed in the lower airways, explained why SARS-CoV-2 causes acute respiratory distress syndrome (ARDS) and respiratory failure. After this, news spread that ACEis and ARBs would be harmful in SARS-CoV-2-infected subjects. To the contrary, compelling evidence exists that the ACE-1/angiotensin(Ang)II/ATR-1 pathway is involved in SARS-CoV-2-induced ARDS, while the ACE-2/Ang(1-7)/ATR2/MasR pathway counteracts the harmful actions of AngII in the lung. A reduced ACE-1/ACE-2 ratio is, in fact, a feature of ARDS that can be rescued by human recombinant ACE-2 and Ang(1-7) administration, thus preventing SARS-CoV-2-induced damage to the lung. Based on the current clinical evidence treatment with ACE-inhibitors I (ACEis) or angiotensin receptor blockers (ARBs) continues to provide cardiovascular and renal protection in patients diagnosed with COVID-19. Discontinuing these medications may therefore be potentially harmful in this patient population.

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Article and author information

Author details

  1. Gian Paolo Rossi

    Department of Medicine-DIMED - Hypertension Unit, University of Padova, Padova, Italy
    For correspondence
    gianpaolo.rossi@unipd.it
    Competing interests
    No competing interests declared.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-7963-0931
  2. Viola Sanga

    Department of Medicine-DIMED - Hypertension Unit, University of Padova, Padova, Italy
    For correspondence
    sangaviola.md@gmail.com
    Competing interests
    No competing interests declared.
  3. Matthias Barton

    University of Zurich, Zurich, Switzerland
    For correspondence
    barton@access.uzh.ch
    Competing interests
    Matthias Barton, Senior Editor, eLife.

Funding

The authors declare that there was no funding for this work.

Reviewing Editor

  1. Mone Zaidi, Icahn School of Medicine at Mount Sinai, United States

Publication history

  1. Received: March 26, 2020
  2. Accepted: April 3, 2020
  3. Accepted Manuscript published: April 6, 2020 (version 1)
  4. Accepted Manuscript updated: April 8, 2020 (version 2)
  5. Accepted Manuscript updated: April 9, 2020 (version 3)
  6. Accepted Manuscript updated: April 15, 2020 (version 4)
  7. Version of Record published: May 4, 2020 (version 5)
  8. Version of Record updated: May 6, 2020 (version 6)

Copyright

© 2020, Rossi et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

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  1. Gian Paolo Rossi
  2. Viola Sanga
  3. Matthias Barton
(2020)
Potential harmful effects of discontinuing ACE-inhibitors and ARBs in COVID-19 patients
eLife 9:e57278.
https://doi.org/10.7554/eLife.57278

Further reading

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    Caigang Liu, Hong Yu ... Yongliang Yang
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    Plasma cell mastitis (PCM) is a nonbacterial breast inflammation with severe and intense clinical manifestation, yet treatment methods for PCM are still rather limited. Although the mechanism of PCM remains unclear, mounting evidence suggests that the dysregulation of immune system is closely associated with the pathogenesis of PCM. Drug combinations or combination therapy could exert improved efficacy and reduced toxicity by hitting multiple discrete cellular targets.

    Methods:

    We have developed a knowledge graph architecture toward immunotherapy and systematic immunity that consists of herbal drug–target interactions with a novel scoring system to select drug combinations based on target-hitting rates and phenotype relativeness. To this end, we employed this knowledge graph to identify an herbal drug combination for PCM and we subsequently evaluated the efficacy of the herbal drug combination in clinical trial.

    Results:

    Our clinical data suggests that the herbal drug combination could significantly reduce the serum level of various inflammatory cytokines, downregulate serum IgA and IgG level, reduce the recurrence rate, and reverse the clinical symptoms of PCM patients with improvements in general health status.

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    In summary, we reported that an herbal drug combination identified by knowledge graph can alleviate the clinical symptoms of PCM patients. We demonstrated that the herbal drug combination holds great promise as an effective remedy for PCM, acting through the regulation of immunoinflammatory pathways and improvement of systematic immune level. In particular, the herbal drug combination could significantly reduce the recurrence rate of PCM, a major obstacle to PCM treatment. Our data suggests that the herbal drug combination is expected to feature prominently in future PCM treatment.

    Funding:

    C. Liu’s lab was supported by grants from the Public Health Science and Technology Project of Shenyang (grant: 22-321-32-18); Y. Yang’s laboratory was supported by the National Natural Science Foundation of China (grant: 81874301), the Fundamental Research Funds for Central University (grant: DUT22YG122), and the Key Research project of ‘be Recruited and be in Command’ in Liaoning Province (2021JH1/10400050).

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    Methods: Here, we conducted a phenome-wide, two-sample Mendelian randomization (MR) analysis using inverse-variance weighted (IVW) regression to systematically infer the causal effects of plasma TG levels on 2,600 disease traits in the European ancestry population of UK Biobank. For replication, we externally tested 221 nominally significant associations (p < 0.05) in an independent cohort from FinnGen. To account for potential horizontal pleiotropy and the influence of invalid instrumental variables, we performed sensitivity analyses using MR-Egger regression, weighted median estimator, and MR-PRESSO. Finally, we used multivariable MR controlling for correlated lipid fractions to distinguish the independent effect of plasma TG levels.

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