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

Currently prescribed drugs in the UK that could upregulate or downregulate ACE2 in COVID-19 disease: a systematic review
Currently prescribed drugs in the UK that could upregulate or downregulate ACE2 in COVID-19 disease: a systematic review
Objective: To review evidence on routinely prescribed drugs in the UK that could upregulate or downregulate 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 with 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 1 April 2020. Methodological quality was assessed using the SYstematic Review Centre for Laboratory animal Experimentation (SYRCLE) risk-of-bias tool for animal studies and Cochrane risk-of-bias tool for human studies.

Results: We screened 3360 titles and included 112 studies with 21 different drug classes identified as influencing ACE2 activity. Ten studies were in humans and one hundred and two were in animal models None examined ACE2 in human lungs. The most frequently examined drugs were angiotensin receptor blockers (ARBs) (n=55) and ACE 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) glucagon-like peptide 1 (GLP-1) agonists (n=2) and Non-steroidal anti-inflammatory drugs (NSAIDs) (n=2).

Conclusions: There is an abundance of the 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 among 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.
public health, respiratory infections, adverse events
2044-6055
Dambha-Miller, Hajira
58961db5-31aa-460e-9394-08590c4b7ba1
Albasri, Ali
733fe375-5968-4d4b-a50a-30c4ceeec8b5
Hodgson, Sam
6e051dfd-5283-4720-8c53-1fae01b34339
Wilcox, Christopher R.
e2c4c36a-e2e5-43a5-9fd6-7198cc15dd53
Khan, Shareen
5c9b2dec-1679-437f-ab52-103b2ff1d2fa
Islam, Nazrul
af39ec49-74b3-4fdb-86cf-bb007e787ca5
Little, Paul
1bf2d1f7-200c-47a5-ab16-fe5a8756a777
Griffin, Simon J.
1f8d5095-3c10-4973-a2c4-84ce6415d118
Dambha-Miller, Hajira
58961db5-31aa-460e-9394-08590c4b7ba1
Albasri, Ali
733fe375-5968-4d4b-a50a-30c4ceeec8b5
Hodgson, Sam
6e051dfd-5283-4720-8c53-1fae01b34339
Wilcox, Christopher R.
e2c4c36a-e2e5-43a5-9fd6-7198cc15dd53
Khan, Shareen
5c9b2dec-1679-437f-ab52-103b2ff1d2fa
Islam, Nazrul
af39ec49-74b3-4fdb-86cf-bb007e787ca5
Little, Paul
1bf2d1f7-200c-47a5-ab16-fe5a8756a777
Griffin, Simon J.
1f8d5095-3c10-4973-a2c4-84ce6415d118

Dambha-Miller, Hajira, Albasri, Ali, Hodgson, Sam, Wilcox, Christopher R., Khan, Shareen, Islam, Nazrul, Little, Paul and Griffin, Simon J. (2020) Currently prescribed drugs in the UK that could upregulate or downregulate ACE2 in COVID-19 disease: a systematic review. BMJ Open, 10 (9). (doi:10.1136/bmjopen-2020-040644).

Record type: Review

Abstract

Objective: To review evidence on routinely prescribed drugs in the UK that could upregulate or downregulate 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 with 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 1 April 2020. Methodological quality was assessed using the SYstematic Review Centre for Laboratory animal Experimentation (SYRCLE) risk-of-bias tool for animal studies and Cochrane risk-of-bias tool for human studies.

Results: We screened 3360 titles and included 112 studies with 21 different drug classes identified as influencing ACE2 activity. Ten studies were in humans and one hundred and two were in animal models None examined ACE2 in human lungs. The most frequently examined drugs were angiotensin receptor blockers (ARBs) (n=55) and ACE 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) glucagon-like peptide 1 (GLP-1) agonists (n=2) and Non-steroidal anti-inflammatory drugs (NSAIDs) (n=2).

Conclusions: There is an abundance of the 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 among 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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More information

Accepted/In Press date: 4 August 2020
e-pub ahead of print date: 14 September 2020
Published date: 14 September 2020
Keywords: public health, respiratory infections, adverse events

Identifiers

Local EPrints ID: 446839
URI: http://eprints.soton.ac.uk/id/eprint/446839
ISSN: 2044-6055
PURE UUID: b8e4861a-4ae2-49a4-b4b3-d61e3688533e
ORCID for Hajira Dambha-Miller: ORCID iD orcid.org/0000-0003-0175-443X

Catalogue record

Date deposited: 24 Feb 2021 17:30
Last modified: 10 Jan 2022 03:17

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Contributors

Author: Ali Albasri
Author: Sam Hodgson
Author: Shareen Khan
Author: Nazrul Islam
Author: Paul Little
Author: Simon J. Griffin

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