Background: An association among the use of angiotensin-converting-enzyme(ACE) inhibitors and angiotensin-receptor blockers(ARBs) with the clinical outcomes of coronavirus disease 2019 (COVID-19) is unclear. Methods: PubMed, EMBASE, and the preprint databases MedRxiv and BioRxiv were searched for relevant studies that assessed the association among inflammation level, application of ACEI/ARB, infection severity and death in patients with COVID-19. Odd risks(OR) and 95% confidence interval (CI) were combined using random-effects or fixed models depending on heterogeneity. Results: Eleven studies were included with a total of 33,483 patients. Our review showed ACEI/ARB therapy might be associated with the reduced inflammatory factor (interleukin-6) and elevated level of immune cells(CD3, CD8). Meta-analysis showed no significant increase in the risk of COVID-19 infection(OR:0.95, 95%CI:0.89-1.05) in patients receiving ACEI/ARB therapy, and ACEI/ARB therapy was associated with a decreased risk of severe COVID-19 (OR:0.75, 95%CI: 0.59-0.96) and mortality (OR:0.52, 95%CI: 0.35-0.79). Subgroup analyses showed that, among the general population, application of ACEI/ARB therapy was associated with reduced risks of all-cause death(OR:0.31, 95%CI: 0.13-0.75), and the risk of severe COVID-19(OR:0.79, 95%CI: 0.60-1.05) infection and COVID-19 infection(OR:0.85, 95% CI: 0.66-1.08) were not increased. Among patients with hypertension, the use of an ACEI/ARB was associated with a lower severity of COVID-19(OR:0.73, 95%CI: 0.51-1.03) and lower mortality(OR:0.57, 95%CI: 0.37-0.87), without evidence of an increased risk of COVID-19 infection(OR:1.00, 95%CI: 0.90-1.12). Conclusion: On the basis of the available evidence, this is the first meta-analysis showed that, in general population, the use of ACEI/ARB therapy was safe without an increased risk of COVID-19 infection and with a decreasing trend of severe COVID-19 infection and lower mortality. In patients with hypertension, the use of ACEI/ARB therapy should be encouraged, without increased risk of COVID-19 inflection, and better prognosis (a decreasing trends of severe COVID-19 and reduced all-cause death). Overall, ACEI/ARB therapy should be continued in patients who are at risk for, or have COVID-19, either in general population or hypertension patients. Our results need to be interpreted with caution considering the potential for residual confounders, and more well-designed studies that control the clinical confounders are necessary to confirm our findings. Key Words COVID-19; ACEI/ARB; SARS-COV-2; pneumonia; infectious disease; lung, hypertension

中文翻译：

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肾素-血管紧张素-醛固酮系统抑制与COVID-19患者的COVID-19风险，炎症水平重度和死亡的关联：快速系统评价和荟萃分析

背景：使用血管紧张素转换酶（ACE）抑制剂和血管紧张素受体阻滞剂（ARB）与2019年冠状病毒病（COVID-19）的临床结局之间的关联尚不清楚。方法：搜索PubMed，EMBASE以及预印数据库MedRxiv和BioRxiv，以评估COVID-19患者的炎症水平，ACEI / ARB应用，感染严重程度和死亡之间的相关性。根据异质性，使用随机效应或固定模型将奇数风险（OR）和95％置信区间（CI）组合在一起。结果：共纳入11项研究，共33,483例患者。我们的综述显示ACEI / ARB治疗可能与炎症因子减少（白介素-6）和免疫细胞（CD3，CD8）水平升高有关。荟萃分析显示接受ACEI / ARB治疗的患者中COVID-19感染的风险没有显着增加（OR：0.95，95％CI：0.89-1.05），而ACEI / ARB治疗与降低严重COVID的风险相关-19（OR：0.75，95％CI：0.59-0.96）和死亡率（OR：0.52，95％CI：0.35-0.79）。亚组分析显示，在普通人群中，ACEI / ARB疗法的使用与全因死亡风险降低（OR：0.31，95％CI：0.13-0.75）和重度COVID-19（OR ：0.79，95％CI：0.60-1.05）感染和COVID-19感染（OR：0.85，95％CI：0.66-1.08）没有增加。在高血压患者中，使用ACEI / ARB与较低的COVID-19严重程度（OR：0.73，95％CI：0.51-1.03）和较低的死亡率（OR：0.57，95％CI：0.37-0.87）相关），而没有证据表明感染COVID-19的风险增加（或：1.00，95％CI：0.90-1.12）。结论：根据现有证据，这是首次荟萃分析表明，在一般人群中，ACEI / ARB疗法的使用是安全的，不会增加COVID-19感染的风险，并且严重COVID的趋势有所降低-19感染并降低死亡率。在高血压患者中，应鼓励使用ACEI / ARB治疗，而不会增加COVID-19感染的风险和更好的预后（严重COVID-19的趋势减少和全因死亡减少）。总体而言，一般人群或高血压患者中，有风险或患有COVID-19的患者应继续接受ACEI / ARB治疗。考虑到可能存在残余混杂因素，我们应谨慎解释我们的结果，为了控制我们的发现，需要进行更多精心设计的研究来控制临床混杂因素。关键词COVID-19；ACEI / ARB；SARS-COV-2; 肺炎; 传染病; 肺，高血压