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Currently prescribed drugs in the UK that could up or downregulate ACE2 in COVID-19 disease: A systematic review

Published version
Peer-reviewed

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Article

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Authors

Dambha-Miller, Hajira  ORCID logo  https://orcid.org/0000-0003-0175-443X
Albasri, Ali 
Hodgson, Sam 
Wilcox, Christopher 
Khan, Shareen 

Abstract

Objective:

To review evidence on routinely prescribed drugs in the UK that could up or downregulate Angiotensin Converting Enzyme 2 (ACE2) and potentially affect COVID-19 disease Design: Systematic review Data source: MEDLINE, EMBASE, CINAHL, the Cochrane Library and Web of Science Study selection: Any design with animal or human models examining a currently prescribed UK drug compared to a control, placebo or sham group, and reporting an effect on ACE2 level, activity or gene expression. Data extraction and synthesis: MEDLINE, EMBASE, CINAHL, the Cochrane Library, Web of Science and OpenGrey from inception to 1st April 2020. Methodological quality was assessed using the SYRCLE's risk of bias tool for animal studies and Cochrane risk of bias tool for human studies.

Results:

We screened 3,360 titles and included 112 studies with 21 different drug classes identified as influencing ACE2 activity. Ten studies were in humans and 102 were in animal models None examined ACE2 in human lungs. The most frequently examined drugs were Angiotensin Receptor Blockers (ARBs) (n= 55) and Angiotensin-Converting Enzyme- Inhibitors (ACE-I) (n= 22). More studies reported upregulation than downregulation with ACE-I (n=22), ARBs (n=55), insulin (n=8), thiazolidinedione (n=7) aldosterone agonists (n=3), statins (n=5), oestrogens (n=5) calcium channel-blockers (n=3) GLP-1 agonists (n=2) and NSAIDs (n=2).

Conclusions:

There is an abundance of academic literature and media reports on the potential of drugs that could attenuate or exacerbate COVID-19 disease. This is leading to trials of repurposed drugs and uncertainty amongst patients and clinicians concerning continuation or cessation of prescribed medications. Our review indicates that the impact of currently prescribed drugs on ACE2 has been poorly studied in-vivo, particularly in human lungs where the SARS-CoV-2 virus appears to enact its pathogenic effects. We found no convincing evidence to justify starting or stopping currently prescribed drugs to influence outcomes of COVID-19 disease.

Description

Keywords

3214 Pharmacology and Pharmaceutical Sciences, 32 Biomedical and Clinical Sciences, Coronaviruses, Infectious Diseases, Emerging Infectious Diseases, 5 Development of treatments and therapeutic interventions, 5.1 Pharmaceuticals, 3 Good Health and Well Being

Journal Title

BMJ Open

Conference Name

Journal ISSN

2044-6055

Volume Title

Publisher

BMJ Journals
Sponsorship
Medical Research Council (MC_UU_12015/4)
MRC (MC_UU_00006/6)
The Southampton, Cambridge and Oxford Primary Care Departments are members of the NIHR School for Primary Care Research and supported by NIHR Research funds. The University of Cambridge has received salary support in respect of SJG from the NHS in the East of England through the Clinical Academic Reserve. SJG is supported by an MRC Epidemiology Unit programme: MC_UU_12015/4. HDM is an NIHR Clinical Lecturer. The views expressed are those of the author(s) and not necessarily those of the NHS, the NIHR or the Department of Health and Social Care