Introduction
Several risk factors linked to poor COVID-19 outcomes have been
identified early on, including cardiovascular diseases such as
hypertension (1). Consequently, the possible impact of
renin-angiotensin-aldosterone system (RAAS) inhibitors on COVID-19
related outcomes has emerged as a topic of interest (2) and their
mechanisms of action– in particular, the potential upregulation of
angiotensin-converting enzyme 2 (ACE2) which is associated with viral
entry into bronchial cells (3). This has resulted in the rapid
dissemination of numerous studies, mostly retrospective observational in
nature, focusing on the risk of COVID-19 infection, disease severity,
and/or disease outcomes in patients being treated with either
angiotensin-converting-enzyme inhibitors (ACEIs)/angiotensin receptor
blockers (ARBs) since early 2020 (4-6).
As was the case in most early COVID-19 related research, the evidence
comprised observational studies with notably small sample sizes and
short durations of follow-up. Resultantly, a number of systematic
reviews were swiftly published in attempt to offer a more substantial
view by aggregating findings of these small-scale studies. These
meta-analyses have offered tentative insights into all three areas of
interest with regards to the use of RAAS inhibitors in times of
COVID-19: (i) risk of infection, usually measured as the share of
positive PCR tests within a study cohort; (ii) risk of severe COVID-19,
with various underlying definitions ranging from hospitalisation due to
the disease to the requirement for mechanical ventilation; and (iii) the
risk of mortality. While there were similarities between some of the
published results – e.g. indicating, in general, no association between
RAAS inhibitor use and risk of COVID-19 infection – other results were
more varied and the findings are still controversial/conflicting (4-6).
A logical next step, besides conducting additional systematic
reviews/meta-analyses, is to perform a systematic review of systematic
reviews (also known as umbrella review), thereby taking advantage of the
availability of high-level evidence and providing an opportunity to
contrast and compare (7). The aim of this umbrella review and
meta-analysis, therefore, was to assess the effect of ACEIs/ARBs on
COVID-19 related outcomes by summarising the currently available,
aggregate evidence.