BACKGROUND Concerns have been raised about the possibility that inhibitors of the renin-angiotensin-aldosterone system (RAAS) could predispose individuals to severe COVID-19; however, epidemiological evidence is lacking. We report the results of a case-population study done in Madrid, Spain, since the outbreak of COVID-19. METHODS In this case-population study, we consecutively selected patients aged 18 years or older with a PCR-confirmed diagnosis of COVID-19 requiring admission to hospital from seven hospitals in Madrid, who had been admitted between March 1 and March 24, 2020. As a reference group, we randomly sampled ten patients per case, individually matched for age, sex, region (ie, Madrid), and date of admission to hospital (month and day; index date), from Base de datos para la Investigación Farmacoepidemiológica en Atención Primaria (BIFAP), a Spanish primary health-care database, in its last available year (2018). We extracted information on comorbidities and prescriptions up to the month before index date (ie, current use) from electronic clinical records of both cases and controls. The outcome of interest was admission to hospital of patients with COVID-19. To minimise confounding by indication, the main analysis focused on assessing the association between COVID-19 requiring admission to hospital and use of RAAS inhibitors compared with use of other antihypertensive drugs. We calculated odds ratios (ORs) and 95% CIs, adjusted for age, sex, and cardiovascular comorbidities and risk factors, using conditional logistic regression. The protocol of the study was registered in the EU electronic Register of Post-Authorisation Studies, EUPAS34437. FINDINGS We collected data for 1139 cases and 11 390 population controls. Among cases, 444 (39·0%) were female and the mean age was 69·1 years (SD 15·4), and despite being matched on sex and age, a significantly higher proportion of cases had pre-existing cardiovascular disease (OR 1·98, 95% CI 1·62-2·41) and risk factors (1·46, 1·23-1·73) than did controls. Compared with users of other antihypertensive drugs, users of RAAS inhibitors had an adjusted OR for COVID-19 requiring admission to hospital of 0·94 (95% CI 0·77-1·15). No increased risk was observed with either angiotensin-converting enzyme inhibitors (adjusted OR 0·80, 0·64-1·00) or angiotensin-receptor blockers (1·10, 0·88-1·37). Sex, age, and background cardiovascular risk did not modify the adjusted OR between use of RAAS inhibitors and COVID-19 requiring admission to hospital, whereas a decreased risk of COVID-19 requiring admission to hospital was found among patients with diabetes who were users of RAAS inhibitors (adjusted OR 0·53, 95% CI 0·34-0·80). The adjusted ORs were similar across severity degrees of COVID-19. INTERPRETATION RAAS inhibitors do not increase the risk of COVID-19 requiring admission to hospital, including fatal cases and those admitted to intensive care units, and should not be discontinued to prevent a severe case of COVID-19. FUNDING Instituto de Salud Carlos III.

中文翻译：

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肾素-血管紧张素-醛固酮系统抑制剂的使用和需要入院的COVID-19的风险：一项病例研究。

背景技术已经出现了关于肾素-血管紧张素-醛固酮系统（RAAS）抑制剂可能使个体易患严重COVID-19的可能性的担忧。但是，缺乏流行病学证据。自COVID-19爆发以来，我们报告了在西班牙马德里进行的一项病例研究的结果。方法在本案例研究中，我们从马德里的7家医院中连续选择了18岁或18岁以上且经PCR确诊需要COVID-19诊断的患者，这些患者已于2020年3月1日至3月24日之间入院。作为参考组，我们每例随机抽取十名患者，分别根据年龄，性别，地区（即马德里）和入院日期（月和日；索引日期）进行匹配，摘自西班牙初级卫生保健数据库巴西基础卫生研究数据库（BIFAP）的最新可用年份（2018年）。我们从病例和对照的电子临床记录中提取了直到索引日期前一个月（即当前使用）的合并症和处方信息。感兴趣的结果是COVID-19患者入院。为了最大程度地减少适应症的混淆，主要分析重点是评估需要住院的COVID-19与使用RAAS抑制剂与使用其他降压药相比的关联。我们使用条件逻辑回归对年龄，性别，心血管合并症和危险因素进行了调整，计算了优势比（OR）和95％CI。该研究的方案已在欧盟授权后研究电子注册簿EUPAS34437中进行了注册。结果我们收集了1139例病例和11 390例人口对照的数据。在这些病例中，有444名（39·0％）为女性，平均年龄为69·1岁（SD 15·4），尽管性别和年龄相匹配，但有较高比例的已患有心血管疾病的病例（ OR 1·98，95％CI 1·62-2·41）和危险因素（1·46、1·23-1·73）。与使用其他降压药的使用者相比，使用RAAS抑制剂的COVID-19的OR值已调整，需要入院率为0·94（95％CI 0·77-1·15）。血管紧张素转换酶抑制剂（调整后的OR 0·80、0·64-1·00）或血管紧张素受体阻滞剂（1·10、0·88-1·37）均未观察到风险增加。性别，年龄，和背景心血管风险并未改变使用RAAS抑制剂与需要入院的COVID-19之间的调整后OR，而在使用RAAS抑制剂的糖尿病患者中发现需要入院的COVID-19风险有所降低（经调整OR 0·53，95％CI 0·34-0·80）。在COVID-19的严重程度中，调整后的OR相似。解释RAAS抑制剂不会增加需要入院的COVID-19的风险，包括致命的病例和重症监护病房的患者，因此不应停用以防止严重的COVID-19病例。资助萨洛德卡洛斯三世研究所。而使用RAAS抑制剂的糖尿病患者中发现需要入院的COVID-19风险降低（校正后OR 0·53，95％CI 0·34-0·80）。调整后的OR在COVID-19的严重程度上相似。解释RAAS抑制剂不会增加需要入院的COVID-19的风险，包括致命的病例和重症监护病房的患者，因此不应停用以防止严重的COVID-19病例。资助萨洛德卡洛斯三世研究所。而使用RAAS抑制剂的糖尿病患者中发现需要入院的COVID-19风险降低（校正后OR 0·53，95％CI 0·34-0·80）。调整后的OR在COVID-19的严重程度上相似。解释RAAS抑制剂不会增加需要入院的COVID-19的风险，包括致命的病例和重症监护病房的患者，因此不应停用以防止严重的COVID-19病例。资助萨洛德卡洛斯三世研究所。并且不应停止使用以防止严重的COVID-19病例。资助萨洛德卡洛斯三世研究所。并且不应停止使用以防止严重的COVID-19病例。资助萨洛德卡洛斯三世研究所。