Association between angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers use and the risk of infection and clinical outcome of COVID-19: a comprehensive systematic review and meta-analysis

Background The effect of using Angiotensin-converting enzyme inhibitors (ACEIs) and Angiotensin-receptor blockers (ARBs) on the risk of coronavirus disease 2019 (COVID-19) is a topic of recent debate. Although studies have examined the potential association between them, the results remain controversial. This study aims to determine the true effect of ACEI/ARBs use on the risk of infection and clinical outcome of COVID-19. Methods Five electronic databases (PubMed, Web of science, Cochrane library, China National Knowledge Infrastructure database, medRxiv preprint server) were retrieved to find eligible studies. Meta-analysis was performed to examine the association between ACEI/ARBs use and the risk of infection and clinical outcome of COVID-19. Results 22 articles containing 157,328 patients were included. Use of ACEI/ARBs was not associated with increased risk of infection (Adjusted OR: 0.96, 95% CI: 0.91-1.01, I2=5.8%) or increased severity (Adjusted OR: 0.90, 95% CI: 0.77-1.05, I2=27.6%) of COVID-19. The use of ACEI/ARBs was associated with lower risk of death from COVID-19 (Adjusted OR: 0.66, 95% CI: 0.44-0.99, I2=57.9%). Similar results of reduced risk of death were also found for ACEI/ARB use in COVID-19 patients with hypertension (Adjusted OR: 0.36, 95% CI: 0.17-0.77, I2=0). Conclusion This study provides evidence that ACEI/ARBs use for COVID-19 patients does not lead to harmful outcomes and may even provide a beneficial role and decrease mortality from COVID-19. Clinicians should not discontinue ACEI/ARBs for patients diagnosed with COVID-19 if they are already on these agents. ### Competing Interest Statement The authors have declared no competing interest. ### Funding Statement This study is financially supported by Hunan Provincial Key Laboratory of Clinical Epidemiology. (2020ZNDXLCL002) ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: This manuscript is a collective work of the listed authors, of course, has been read and approved by all the authors. In addition, this paper has not been previously published, not currently under review by another journal and considered for publication elsewhere. All authors have declared no conflict of interest in this study and approved finally version of manuscript.Guangbo Qu and Chenyu Sun contributed to the study design, the development of research protocol, and supervision of whole steps of this study. Liqin Shu designed the search strategy and conducted the literature search. Guangbo Qu and Liqin Shu conducted study selection, data extraction and quality assessment of included studies. Chenyu Sun checked the literature search and data extraction. Guangbo Qu performed data analyses and created tables and figures. Guangbo Qu and Chenyu Sun took responsibility for the interpretation of results. Guangbo Qu wrote the first draft of manuscript. Liqin Shu, Evelyn J. Song, Ce Cheng, Dhiran Verghese, John Patrick Uy, Qin Zhou, Hongru Yang, Zhichun Guo, Mengshi Chen, Chenyu Sun contributed to the edition and revision of the draft of manuscript. All authors reviewed and approved final version of the manuscript All necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines and uploaded the relevant EQUATOR Network research reporting checklist(s) and other pertinent material as supplementary files, if applicable. Yes Data will be available on request.