Key result
A systematic review of 112 studies found no convincing evidence in human lungs to justify starting or stopping currently prescribed drugs like ACE inhibitors or ARBs to influence COVID-19 outcomes.
Why the study?
To review evidence on routinely prescribed drugs in the UK that could upregulate or downregulate ACE2 and potentially affect COVID-19 disease.
Do currently prescribed UK drugs affect ACE2 levels, activity, or gene expression in human or animal models?
Systematic Review (n=112)
Do currently prescribed UK drugs affect ACE2 levels, activity, or gene expression in human or animal models?
There is no convincing evidence to justify starting or stopping currently prescribed drugs (such as ACE inhibitors or ARBs) to influence COVID-19 outcomes based on ACE2 effects.
No evidence supports altering ACE-I or ARB prescriptions for COVID-19; leaves open effects on human lung ACE2.
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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Dambha‐Miller et al. (2020) conducted a systematic review in COVID-19 (n=112). Currently prescribed UK drugs (including ACE-I and ARBs) vs. Control, placebo or sham group was evaluated on Effect on ACE2 level, activity or gene expression. A systematic review of 112 studies found no convincing evidence in human lungs to justify starting or stopping currently prescribed drugs like ACE inhibitors or ARBs to influence COVID-19 outcomes.
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