The content of this evidence review was up to date on 1 April 2020. New evidence may have been published since then. See summaries of product characteristics (SPCs), British national formulary (BNF) or the MHRA or NICE websites for up-to-date prescribing information.
Angiotensin-converting enzyme 2 (ACE2) is abundant in the epithelial cells of the lung where it acts as a cell receptor and forms part of the renin-angiotensin pathway. Both angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) act on the renin-angiotensin pathway and are thought to upregulate ACE2 expression. ACE2 has 2 possible roles in COVID-19:
Coronaviruses, including those responsible for Middle East respiratory syndrome (MERS), severe acute respiratory syndrome (SARS), and coronavirus disease (COVID-19), bind to ACE2 to gain access to the epithelial cells. Therefore, upregulation of ACE2 could theoretically increase a person's risk of COVID-19 or developing more severe COVID-19.
Upregulation of ACE2 has been shown to be protective in acute respiratory disease and downregulation of ACE2 has been implicated in lung injury.
The purpose of this review is to assess the best available evidence to determine:
If there is any increased risk of developing COVID-19 due to ACEIs or ARBs
If ACEIs or ARBs can lead to an increased risk of developing more severe symptoms of COVID-19.
This review identified 2 retrospective observational studies that met the inclusion criteria. One paper reported no statistically significant difference in the proportion of patients using an ACEI or an ARB who had critical and non-critical COVID-19 (3/16 [18.8%] compared with 19/96 [19.8%] respectively, p=1.00) (Peng et al 2020).
Alburikan et al 2020 reported that, in patients tested for MERS-CoV, ACEI or ARB prescribing was not associated with an increase or decrease in the likelihood of testing positive for MERS-CoV. ACEIs or ARBs were prescribed in 16% of suspected cases and 15% of confirmed cases, p=0.40.
Whilst no increase in risk of developing COVID-19 or more severe disease was found in the 2 observational studies included, the studies were of poor quality and subject to bias and confounding. Therefore, conclusions cannot be drawn on whether ACEIs or ARBs increase the risk of developing COVID-19 or developing more severe COVID-19.