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 huma...
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| Format: | Article |
| Language: | English |
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BMJ Publishing Group
2020-09-01
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| Series: | BMJ Open |
| Online Access: | https://bmjopen.bmj.com/content/10/9/e040644.full |
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| _version_ | 1841554271534841856 |
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| author | Paul Little Simon J Griffin Hajira Dambha-Miller Nazrul Islam Ali Albasri Christopher R Wilcox Sam Hodgson Shareen Khan |
| author_facet | Paul Little Simon J Griffin Hajira Dambha-Miller Nazrul Islam Ali Albasri Christopher R Wilcox Sam Hodgson Shareen Khan |
| author_sort | Paul Little |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-a351502e6c264453aa99477ffc7e8fa0 |
| institution | Kabale University |
| issn | 2044-6055 |
| language | English |
| publishDate | 2020-09-01 |
| publisher | BMJ Publishing Group |
| record_format | Article |
| series | BMJ Open |
| spelling | doaj-art-a351502e6c264453aa99477ffc7e8fa02025-01-08T16:20:13ZengBMJ Publishing GroupBMJ Open2044-60552020-09-0110910.1136/bmjopen-2020-040644Currently prescribed drugs in the UK that could upregulate or downregulate ACE2 in COVID-19 disease: a systematic reviewPaul Little0Simon J Griffin1Hajira Dambha-Miller2Nazrul Islam3Ali Albasri4Christopher R Wilcox5Sam Hodgson6Shareen Khan71 University of Southampton, Southampton, UKUniversity of Cambridge, Cambridge, UKMRC Epidemiology Unit, University of Cambridge, Cambridge, UKDepartment of Population Health, University of Oxford, Oxford, UK5Novartis Pharmaceuticals UK LimitedPrimary Care Research Centre, University of Southampton, Southampton, UKQueen Mary University of London, London, UKOxford University Hospitals NHS Trust, Oxford, UKObjective 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.https://bmjopen.bmj.com/content/10/9/e040644.full |
| spellingShingle | Paul Little Simon J Griffin Hajira Dambha-Miller Nazrul Islam Ali Albasri Christopher R Wilcox Sam Hodgson Shareen Khan Currently prescribed drugs in the UK that could upregulate or downregulate ACE2 in COVID-19 disease: a systematic review BMJ Open |
| title | Currently prescribed drugs in the UK that could upregulate or downregulate ACE2 in COVID-19 disease: a systematic review |
| title_full | Currently prescribed drugs in the UK that could upregulate or downregulate ACE2 in COVID-19 disease: a systematic review |
| title_fullStr | Currently prescribed drugs in the UK that could upregulate or downregulate ACE2 in COVID-19 disease: a systematic review |
| title_full_unstemmed | Currently prescribed drugs in the UK that could upregulate or downregulate ACE2 in COVID-19 disease: a systematic review |
| title_short | Currently prescribed drugs in the UK that could upregulate or downregulate ACE2 in COVID-19 disease: a systematic review |
| title_sort | currently prescribed drugs in the uk that could upregulate or downregulate ace2 in covid 19 disease a systematic review |
| url | https://bmjopen.bmj.com/content/10/9/e040644.full |
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