SynthesisBMJ open2020
Currently prescribed drugs in the UK that could upregulate or downregulate ACE2 in COVID-19 disease: a systematic review.
Synthesis in BMJ open, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers, 2 of them syntheses that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
20 citing papers in PubMed, 2 syntheses or guidelines pooled it, 30 citations in OpenAlex.
- Meta-analysis evaluating the risk of respiratory tract infections and acute respiratory distress syndrome with glucagon-like peptide-1 receptor agonists in cardiovascular outcome trials: Useful implications for the COVID-19 pandemic.Revista clinica espanola · 2022Pooled it
- NSAIDs and COVID-19: A Systematic Review and Meta-analysis.Drug safety · 2021Pooled it
- Circulating Cardiovascular Proteomic Associations With Genetics and Disease.Circulation. Genomic and precision medicine · 2025Article
- A Transformer-Based Framework for Counterfactual Estimation of Antihypertensive Treatment Effect on COVID-19 Infection Risk - A Proof-of-Concept Study.American journal of hypertension · 2025Article
- Mortality from angiotensin-converting enzyme-inhibitors and angiotensin receptor blockers in people infected with COVID-19: a cohort study of 3.7 million people.Family practice · 2023Article
- Angiotensin-converting enzyme 2 and transmembrane protease serine 2 in female and male patients with end-stage kidney disease.European journal of clinical investigation · 2022Article
- Actions of Novel Angiotensin Receptor Blocking Drugs, Bisartans, Relevant for COVID-19 Therapy: Biased Agonism at Angiotensin Receptors and the Beneficial Effects of Neprilysin in the Renin Angiotensin System.Molecules (Basel, Switzerland) · 2022Article
- Diminazene Aceturate Reduces Angiotensin II Constriction and Interacts with the Spike Protein of Severe Acute Respiratory Syndrome Coronavirus 2.Biomedicines · 2022Article
- [Meta-analysis evaluating the risk of respiratory tract infections and acute respiratory distress syndrome with glucagon-like peptide-1 receptor agonists in cardiovascular outcome trials: Useful implications for the COVID-19 pandemic].Revista clinica espanola · 2022Article
- The COVID-19 explorer-An integrated, whole patient knowledge model of COVID-19 disease.Frontiers in molecular medicine · 2022Article
- Discovery of a new generation of angiotensin receptor blocking drugs: Receptor mechanisms and in silico binding to enzymes relevant to SARS-CoV-2.Computational and structural biotechnology journal · 2022Article
- Whole patient knowledge modeling of COVID-19 symptomatology reveals common molecular mechanisms.Frontiers in molecular medicine · 2022Article
- Soluble angiotensin-converting enzyme levels in heart failure or acute coronary syndrome: revisiting its modulation and prognosis value.Journal of molecular medicine (Berlin, Germany) · 2021Observational
- Antihypertensive medications and COVID-19 diagnosis and mortality: Population-based case-control analysis in the United Kingdom.British journal of clinical pharmacology · 2021Article
- Factors regulating dynamics of angiotensin-converting enzyme-2 (ACE2), the gateway of SARS-CoV-2: Epigenetic modifications and therapeutic interventions by epidrugs.Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie · 2021Review
- Interactions between diabetes and COVID-19: A narrative review.World journal of diabetes · 2021Review
- Glucagon-like peptide-1 receptor agonists in the era of COVID-19: Friend or foe?Clinical obesity · 2021Review
- From Angiotensin II to Cyclic Peptides and Angiotensin Receptor Blockers (ARBs): Perspectives of ARBs in COVID-19 Therapy.Molecules (Basel, Switzerland) · 2021Review
- Covid-19 and Diabetes: A Complex Bidirectional Relationship.Frontiers in endocrinology · 2020Review
- Some Questions to Our Chinese Colleagues Pioneering Research Into Coronavirus Disease 2019 (COVID-19).Frontiers in medicine · 2020Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
8 authors at 4 institutions in 1 country.
Funding
Abstract
objectiveTo review evidence on routinely prescribed drugs in the UK that could upregulate or downregulate ACE2 and potentially affect COVID-19 disease.
designSystematic 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.
resultsWe 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).
conclusionsThere 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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What Socratic holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.