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

BackgroundThe 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. AimTo 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 settingSystematic review of studies published in MEDLINE, EMBASE, CINAHL, the Cochrane Library and Web of Science from inception to April 1st 2020. MethodA 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. ResultsData will be reported in summary tables and narrative synthesis. ConclusionThis 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.