Study characteristics
The literature search identified 452 articles. However, only 27 studies were eligible for inclusion (Figure 1). A total of 72,372 patients were included in these 27 studies of which 10,197 (14.1%) patients were on ACEIs or ARBs. The average age of the population in these studies was 61 years and men represented 52.24% of them (Table 1). Twenty-one studies (77.8%) focused on comparing COVID-19 related outcomes between ACEI/ARB users vs. non-users among patients with COVID-19 while the remining six studies (22.2%) focused on comparing outcomes between ACEIs/ARBs users in patients with and without COVID-19 infection (Table 1). ACEIs/ARBs in the included studies were indicated for a wide range of chronic conditions such as hypertension, coronary artery diseases, heart failure, diabetes or chronic kidney disease.
In terms of outcomes, nine studies (33.3%) reported three to five COVID-19 related outcomes (20, 23, 25, 26, 37-41), while another nine studies (33.3%) reported only two outcomes (17, 19, 22, 24, 27, 42-45) with another one-third reported only one outcome [19,22,29,46-51]. Overall, the 27 studies reported data on 15 unique outcomes including death in 12 studies (18, 21, 28, 46-51), ICU admission in seven studies (23, 25, 37-41), death/ICU admission as a composite outcome in four studies (21, 37, 42, 51), risk of acquiring COVID-19 infection in nine studies (22, 25, 26, 39-41, 45, 46, 50), risk of severe COVID-19 infection in seven studies (17-19, 22, 24, 45, 47), risk of severe pneumonia in two studies (26, 48), risk of hospitalisation in eight studies (26, 39-44, 49), hospital discharge in three studies (23, 26, 27), use of ventilator in four studies (19, 23, 38, 41), duration of hospital stay in two studies (25, 26), and each of acute respiratory distress syndrome (ARDS), septic shock, cardiac shock, acute kidney injury (20), and hospital readmission (23) in one study, respectively. In terms of the exposure, the effects of ACEIs and ARBs were assessed as one class (ACEIs/ARBs) in 17 studies (63%) (17, 20, 22-28, 37, 40, 41, 44, 47, 48, 50, 51), as separate classes in five studies (18.5%) 52, 74, 78, 80, 84), and both as one and separate classes in another five studies (18, 19, 38, 42, 46).
The majority of the 27 eligible studies were conducted in Asia (44.4%, n=12 with 10 studies from China, one from each of in Korea and Israel), followed by nine studies (33.3%) from Europe (four in Italy, three in the United Kingdom and one from each of France and Belgium) and the remaining six (22.3%) from the USA. Furthermore, the reported measure of effects were crude/un-adjusted measures in the majority of the studies (77.8%, n=21) (18, 19, 21-28, 37-43, 45, 50, 51); with most of them (59.3%, n=16) being non-peer reviewed articles published as preprints on medRivix (24, 26, 27, 37-40, 42-45, 47-51), and only four rated as a good quality studies based on the Newcastle-Ottawa Quality Assessment risk of bias (21, 37, 44, 45) (Table 2).