Drug treatments affecting ACE2 in COVID-19 infection: a systematic review protocol

Abstract Background: The SARS-CoV-2 virus causing COVID-19 binds human angiotensin-converting enzyme 2 (ACE2) receptors in human tissues. ACE2 expression may be associated with COVID-19 infection and mortality rates. Routinely prescribed drugs which up- or down-regulate ACE2 expression are therefore of critical research interest as agents which might promote or reduce risk of COVID-19 infection in a susceptible population. Aim: To review evidence on routinely prescribed drug treatments in the UK that could up- or down-regulate ACE2 and potentially affect COVID-19 infection. Design and setting: Systematic review of studies published in MEDLINE, EMBASE, CINAHL, the Cochrane Library and Web of Science from inception to April 1st 2020. Method: A systematic review will be conducted in line with PRISMA guidelines. Inclusion criteria will be: i) assess effect of drug exposure on ACE2 level; ii) drug is included in British National Formulary (BNF) and therefore available to prescribe in UK; iii) a control, placebo or sham group is included as comparator. Exclusion criteria will be: i) ACE2 measurement in utero; ii) ACE2 measurement in children under 18 years; iii) drug not in BNF; iv) review article. Quality will be assessed using the Cochrane risk of bias tool for human studies, and the SYRCLE risk of bias tool for animal studies. Results: Data will be reported in summary tables and narrative synthesis. Conclusion: This systematic review will identify drug therapies which may increase or decrease ACE2 expression. This might identify medications increasing risk of COVID-19 transmission, or as targets for intervention in mitigating transmission.