Aim To provide a comprehensive assessment of the effect of angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor II blockers (ARBs) on COVID-19 related outcomes by summarising the currently available evidence. Methods This was an umbrella review of systematic reviews/meta-analysis conducted using Medline (OVID), Embase, Scopus, Cochrane library and medRxiv from inception to 1st February 2021. Systematic reviews with meta-analysis that evaluated the effect of ACEIs/ARBs on COVID-19 related clinical outcomes were eligible. Studies’ quality was appraised using the AMSTAR 2 Critical Appraisal Tool. Data were analysed using the random-effects modelling including several sub-group analyses. Heterogenicity was assessed using I2 statistic. The study protocol was registered in PROSPERO (CRD42021233398). Results Overall, 47 reviews were eligible for inclusion. Out of the nine COVID-19 outcomes evaluated, there was significant associations between ACEIs/ARBs use and each of death (OR=0.80, 95%CI=0.75-0.86; I2=51.9%), death/ICU admission as composite outcome (OR=0.86, 95%CI=0.80-0.92; I2=43.9%), severe COVID-19 (OR=0.86, 95%CI=0.78-0.95; I2=68%), and hospitalisation (OR=1.23, 95%CI=1.04-1.46; I2= 76.4%). The significant reduction in death/ICU admission, however, was higher among studies which presented adjusted measure of effects (OR=0.63, 95%CI=0.47-0.84) and were of moderate quality (OR=0.74, 95%CI=0.63-0.85). There was no evidence of any significant association between ACEIs, or ARBs and COVID-19 outcomes. Conclusions Collective evidence from observational studies indicate a good quality evidence on the significant association between ACEIs/ARBs use and reduction in death and death/ICU admission, but poor-quality evidence on both reducing severe COVID-19 and increasing hospitalisation. Our findings further support the current recommendations of not discontinuing ACEIs/ARBs therapy in patients with COVID-19.

Aim To provide a comprehensive/updated evaluation of the effect of ACEIs/ARBs on COVID-19 related-clinical outcomes, including exploration of inter-class differences between ACEIs and ARBs. Methods This was a systematic review/meta-analysis conducted in Medline (OVID), Embase, Scopus, Cochrane library and medRxiv from inception to 22nd May-2020. English studies that evaluated the effect of ACEIs/ARBs among patients with COVID-19 were included. The study outcomes included any COVID-19 related-clinical outcomes. Studies’ quality was appraised using the Newcastle-Ottawa Scale. Data were analysed using the random-effects modelling stratified by ACEIs/ARBs, ACEIs, and ARBs. Heterogenicity was assessed using I2 statistic. Several sub-group analyses were conducted to explore the impact of potential confounders. Results Out of the identified 452 studies, 27 studies were eligible for inclusion. The pooled analyses showed non-significant associations between ACEIs/ARBs and death (OR:0.97, 95%CI:0.75,1.27), ICU admission (OR:1.09;95%CI:0.65,1.81), death/ICU admission (OR:0.67; 95%CI:0.52,0.86), risk of COVID-19 infection (OR:1.01; 95%CI:0.93,1.10), severe infection (OR:0.78; 95%CI:0.53,1.15) and hospitalisation (OR:1.15; 95%CI:0.81,1.65). However, the sub-group analyses indicated different results such as significant association between ACEIs/ARBs and hospitalisation among USA studies (OR:1.59; 95%CI:1.03,2.44), peer-reviewed (OR:1.93, 95%CI:1.38,2.71), good quality and studies which reported adjusted measure of effect (OR:1.30, 95%CI:1.10,1.50). Significant differences were found between ACEIs and ARBs with the latter being significantly associated with lower risk of acquiring COVID-19 infection (OR:0.24; 95%CI: 0.17,0.34). Conclusions High-quality evidence exist for the effect of ACEIs/ARBs on some COVID-19 clinical outcomes. For the first time, we provided evidence, albeit of low quality, on inter-class differences between ACEIs and ARBs for some of the reported clinical outcome.