Characteristics of 20 included observational studies
| No. | Study | Region | Eligibility criteria | N | Age, mean | Male, % | Exposure to intervention | Definition of severe disease |
| 1 | Ashraf MA. et al 35 | Iran | The patients confirmed with COVID-19 who were admitted to hospital | 100 ACEI/ARB group: 19 | 58* | 64.6 | Medical records on ACEI or ARB was reviewed | One of the following conditions: reduced consciousness, RR ≥30/min, BP <90/60, Multilobular infiltration, hypoxaemia |
| 2 | Bean D. et al 39 | UK | Patients with COVID-19 symptomatic and requiring inpatient admission | 205 ACEI/ARB group: 46 | 63.0 ACEI/ARB group: 72.7 Non-ACEI/ARB group: 60.1 | 51.7 ACEI/ARB group: 54.3 Non-ACEI/ARB group: 44.6 | Exposure to ACEI or ARB within 7 days before symptoms or during inpatient treatment | Death or admission to a critical care unit for organ-support within 7 days of symptoms onset |
| 3 | Benelli G. et al 32 | Crema, Italy | The patients diagnosed with COVID-19 who were admitted to hospital | 411 ACEI/ARB group: 110 | 66.8 | 66.6 | Data on medication history of ACEI or ARB was extracted from electric medical record | N/A (although CPAP/NIV use, ICU admission and death was evaluated, those outcomes can be overlapped) |
| 4 | Caraballo C. et al 36 | USA | The adult patients (aged ≥18 years) with heart failure who were admitted to hospital for the treatment of confirmed COVID-19 | 206 ACEI/ARB group: 172 | 78* | 45.1 | Exposure to ACEI or ARB before and during hospitalisation | N/A |
| 5 | Feng Y et al 12 | Multicentre, China | All the patients diagnosed with COVID-19 who visited the hospitals designated for the treatment of COVID-19 | 113 (476) ACEI/ARB group: 33 | (53.0)*† | (56.9)† | Data on medication history of ACEI or ARB was extracted from electric medical record | One of the following conditions: RR ≥30/min, O2 saturation at rest ≤93%, PF ratio ≤300 (WHO-China criteria) |
| 6 | Feng Z. et al38* | Multicentre, China | All the adult patients with confirmed COVID-19 with available clinical or imaging data who were treated at hospital | 65 (564) ACEI/ARB group: 16 | 61.5 (47)* ACEI/ARB group: 57* Non-ACEI/ARB group: 63* | 50.8 (50.4) ACEI/ARB group: 62.5 Non-ACEI/ARB group: 46.9 | Data on medication history of ACEI or ARB was extracted from electric medical record | One of the following conditions: RR ≥30/min, O2 saturation at rest ≤93%, PF ratio ≤300 (WHO-China criteria) |
| 7 | Ip A. et al 33 | USA | The hypertensive patients diagnosed with COVID-19 who were admitted to hospital | 1129 ACEI/ARB group: 460 | – | – | Data on medication history of ACEI or ARB was extracted from electric medical record | N/A |
| 8 | Lee H. et al 37 | South Korea | The patients diagnosed with COVID-19 who were admitted to hospital or isolated | 8266 ACEI/ARB group: 977 | 44.4 ACEI/ARB group: 41.6 Non-ACEI/ARB group: 64.8 | 38.5 ACEI/ARB group: 56.4 Non-ACEI/ARB group: 37.8 | Data on medication history of ACEI or ARB was extracted from electric medical record | N/A (severe disease was not evaluated) |
| 9 | Li J. et al 1 | Wuhan, China | The hypertensive patients diagnosed with COVID-19 who were admitted to hospital | 362 ACEI/ARB group: 115 | 66* ACEI/ARB group: 65* Non-ACEI/ARB group: 67* | 52.2 ACEI/ARB group: 59.1 Non-ACEI/ARB group: 49.0 | Use of these drugs at the time of admission that continued through hospitalisation | One of the following conditions: RR ≥30/min, O2 saturation at rest ≤93%, PF ratio ≤300 (WHO-China criteria) |
| 10 | Mancia G. et al 14 | Italy | The beneficiaries of the Regional Health Service (aged ≥40 years) diagnosed with COVID-19 | 6272 ACEI/ARB group: 2896 | 68 | 36.7 | Data on medication history of ACEI or ARB was extracted from claim data | Assisted ventilation or death |
| 11 | Mehra MR. et al 15 | International (Asia, Europe and North America) | The patients diagnosed with COVID-19 who were admitted to hospital | 8910 ACEI/ARB group: 1326 | 49.1 | 59.9 | Exposure to ACEI or ARB at the time of hospitalisation | N/A |
| 12 | Meng J. et al 16 | Shenzhen, China | The hypertensive patients diagnosed with COVID-19 who were admitted to hospital and took antihypertensive drugs | 42 ACEI/ARB group: 17 | 62.0 ACEI/ARB group: 61.9 Non-ACEI/ARB group: 62.1 | 57.1 ACEI/ARB group: 47.1 Non-ACEI/ARB group: 60.0 | Exposure to ACEI or ARB during hospitalisation | One of the following conditions: RR ≥30/min, O2 saturation at rest ≤93%, PF ratio ≤300 (WHO-China criteria) |
| 13 | Peng Y. et al 17 | Wuhan, China | The adult patients (aged ≥18 years) with cardiovascular disease who were diagnosed with COVID-19 and treated in hospital The patients with systemic diseases, liver disease or kidney abnormalities were excluded | 112 ACEI/ARB group: 22 | 62.0 | 47.3 | Data on medication history of ACEI or ARB was extracted from electric medical record | One of the following conditions: RR ≥30/min, O2 saturation at rest ≤93%, PF ratio ≤300 (WHO-China criteria) |
| 14 | Rentsch CT.et al 40 | USA | Among the eligible patients in VA who underwent COVID-19 tests, only patients with a positive test for COVID-19 were evaluated in our study | 585 ACEI/ARB group: 255 | 66.1 | 95.4 | Data on medication history of ACEI or ARB was extracted from electric medical record | Intensive care |
| 15 | Reynolds HR. et al 18 | USA | Propensity score-matched patients with a positive test for COVID-19 | 2211 (5894) ACEI/ARB group: 1110 | -† | -† | Data on medication history of ACEI or ARB was extracted from claim data | Admission to the intensive care unit, the use of non-invasive or invasive mechanical ventilation or death |
| 16 | Tedeschi S. et al 19 | Italy | Prospectively enrolled adult patients with hypertension who were hospitalised and diagnosed with a microbiologically confirmed COVID-19 | 311 ACEI/ARB group: 175 | 76* | 72.3 | Patients received antihypertensive medication including ACEI or ARB during hospitalisation | N/A |
| 17 | Yan H. et al 41 | Zhejiang, China | All adult patients diagnosed with COVID-19 | 137 (610) ACEI/ARB group: 58 | (48.8)† | (51.1)† | Data on medication history of ACEI or ARB was extracted from electric medical record | One of the following conditions: RR ≥30/min, O2 saturation at rest ≤93%, PF ratio ≤300, respiratory failure requiring mechanical ventilation, shock and requiring ICU admission requirement due to multiple organ failure (WHO-China criteria) |
| 18 | Yang G. et al 20 | Wuhan, China | The patients diagnosed with COVID-19 who were admitted to hospital | 126 (251) ACEI/ARB group: 43 | 66 (66)* ACEI/ARB group: 65* Non-ACEI/ARB group: 67* | 49.2 (49.0) ACEI/ARB group: 48.8 Non-ACEI/ARB group: 49.4 | Exposure to ACEI or ARB prior to admission and during hospital stay | One of the following conditions: RR ≥30/min, O2 saturation at rest ≤93%, PF ratio ≤300 (WHO-China criteria) |
| 19 | Zeng Z. et al 34 | Wuhan, China | The hospitalised patients suspected and confirmed of patients with COVID-19 who were aged <18 years, whose entire stay in hospital lasted for <48 hours were excluded | 75 (274) ACEI/ARB group: 28 | 67 (60) ACEI/ARB group: 64 Non-ACEI/ARB group: 69 | 46.7 (54.7) ACEI/ARB group: 42.9 Non-ACEI/ARB group: 48.9 | Data on medication history of ACEI or ARB were extracted from electric medical record | One of the following conditions: septic shock, mechanical ventilation Three of the following conditions: RR ≥30/min, PF ratio ≤250, multiple infiltration, altered mentality, BUN ≥20 mg/dL, WBC <4000 cells/μL, platelet <100 000/μL, body temperature <36°C, hypotension requiring fluid resuscitation (ATS/IDSA criteria for severe pneumonia) |
| 20 | Zhang P. et a 21 | Multicentre, China | The hypertensive adults (aged 18–74 years) diagnosed with COVID-19 who were admitted to hospital The patients with incomplete medical records, pregnancy, lethal organ injury, decompensated or end-stage disease, AIDS or malignancy were excluded | 1128 ACEI/ARB group: 188 | 64* ACEI/ARB group: 64 Non-ACEI/ARB group: 64 | 53.5 ACEI/ARB group: 53.2 Non-ACEI/ARB group: 53.5 | Exposure to ACEI or ARB during hospitalisation | N/A (although acute respiratory syndrome, septic shock, disseminated intravascular coagulopathy and acute kidney injury were evaluated, those outcomes can be overlapped) |
Some studies evaluated the association between ACEI/ARB use and severe disease or mortality only in the subgroup patients with hypertension. If the information is available, we described the information of hypertensive patients first, and then the information of all patients in the bracket.
*Only median value was reported.
†Only the values of the whole patient cohort were available; the values of the subjects analysed in the study were not presented.
ACEI, ACE inhibitor; ARB, angiotensin II receptor antagonist; ATS, American Thoracic Society; BP, blood pressure; BUN, blood urea nitrogen; IDSA, Infectious Diseases Society of America; N/A, not available; NIV, non-invasive ventilation; PF ratio, PaO2/FiO2; RR, respiratory ratio; WBC, white blood cell.