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

Currently prescribed drugs in the UK that could up or downregulate ACE2 in COVID-19 disease: a systematic review
Currently prescribed drugs in the UK that could up or downregulate ACE2 in COVID-19 disease: a systematic review
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.
covid-19, ace-i, mortality
2044-6055
Dambha-Miller, Hajira
58961db5-31aa-460e-9394-08590c4b7ba1
Little, Paul
1bf2d1f7-200c-47a5-ab16-fe5a8756a777
Hodgson, Sam
6e051dfd-5283-4720-8c53-1fae01b34339
Wilcox, Christopher R.
dd406779-15d1-494e-b3f3-38db0e453be7
Dambha-Miller, Hajira
58961db5-31aa-460e-9394-08590c4b7ba1
Little, Paul
1bf2d1f7-200c-47a5-ab16-fe5a8756a777
Hodgson, Sam
6e051dfd-5283-4720-8c53-1fae01b34339
Wilcox, Christopher R.
dd406779-15d1-494e-b3f3-38db0e453be7

Dambha-Miller, Hajira, Little, Paul, Hodgson, Sam and Wilcox, Christopher R. (2020) Currently prescribed drugs in the UK that could up or downregulate ACE2 in COVID-19 disease: a systematic review. BMJ Open. (In Press)

Record type: Article

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.

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Accepted/In Press date: 4 August 2020
Keywords: covid-19, ace-i, mortality

Identifiers

Local EPrints ID: 443047
URI: http://eprints.soton.ac.uk/id/eprint/443047
ISSN: 2044-6055
PURE UUID: e72f9a47-faa2-44d5-89e4-b1bfa78da11c
ORCID for Hajira Dambha-Miller: ORCID iD orcid.org/0000-0003-0175-443X

Catalogue record

Date deposited: 06 Aug 2020 16:36
Last modified: 13 Dec 2021 06:12

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Contributors

Author: Paul Little
Author: Sam Hodgson
Author: Christopher R. Wilcox

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