Currently prescribed drugs in the UK that could upregulate or downregulate ACE2 in COVID-19 disease: a systematic review.
BMJ Open
; 10(9): e040644, 2020 09 14.
Article
in English
| MEDLINE | ID: covidwho-767942
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 ANDSYNTHESIS:
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.Keywords
Full text:
Available
Collection:
International databases
Database:
MEDLINE
Main subject:
Pneumonia, Viral
/
Angiotensin-Converting Enzyme Inhibitors
/
Calcium Channel Blockers
/
Coronavirus Infections
/
Peptidyl-Dipeptidase A
/
Hydroxymethylglutaryl-CoA Reductase Inhibitors
/
Estrogens
/
Angiotensin Receptor Antagonists
/
Pandemics
/
Hypoglycemic Agents
Type of study:
Prognostic study
/
Randomized controlled trials
/
Reviews
/
Systematic review/Meta Analysis
Limits:
Humans
Country/Region as subject:
Europa
Language:
English
Journal:
BMJ Open
Year:
2020
Document Type:
Article
Affiliation country:
Bmjopen-2020-040644
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