Effect of Spironolactone on COVID-19 in Patients With Underlying Liver Cirrhosis: A Nationwide Case-Control Study in South Korea
Dongsub Jeon, Minkook Son, Jonggi Choi
Frontiers in Medicine, doi:10.3389/fmed.2021.629176
Purpose: On the basis that spironolactone is involved in ACE2 expression and TMPRSS2 activity, previous studies have suggested that spironolactone may influence the infectivity of COVID-19. Research has suggested that cell entry of SARS-CoV-2, the virus that induces COVID-19, is associated with the ACE2 receptor and TMPRSS2. The purpose of this study was to investigate whether spironolactone has a protective effect against COVID-19 and the development of associated complications in patients with liver cirrhosis. Methods: We conducted a nationwide case-control study on liver cirrhosis patients with or without COVID-19 from the population-based data acquired from the National Health Insurance Systems of Republic of Korea. After 1:5 case-control matching, multivariable adjusted conditional logistic regression analysis was performed. Results: Among the patients with liver cirrhosis, the case group with COVID-19 was found to be significantly less exposed to spironolactone compared with the control group without COVID-19. The adjusted odds ratio (OR) and 95% confidence interval (CI) between the two groups was 0.20 (0.07-0.54). In addition, regardless of cumulative dose of spironolactone, exposure to spironolactone was associated with lower COVID-19 infection. In terms of the development of complications due to COVID-19, spironolactone did not show any significant association between the patients with and without complications (P = 0.43). The adjusted OR and 95% CI between the two groups was 1.714 (0.246-11.938).
Conclusion: We conclude that spironolactone may reduce susceptibility to COVID-19 but does not affect the development of its associated complications; however, further studies are needed to confirm the exact association between spironolactone and COVID-19 infection.
ETHICS STATEMENT The studies involving human participants were reviewed and approved by Institutional Review Board of Asan Medical Center, Seoul, Republic of Korea (IRB number: 2020-1153). Written informed consent for participation was not required for this study in accordance with the national legislation and the institutional requirements.
AUTHOR CONTRIBUTIONS DJ, MS, and JC were responsible for the conception and design of the study, acquisition, analysis and interpretation of the data, and drafting of the manuscript. MS performed the statistical analyses. All authors have full access to all data used in the study and take responsibility for the integrity of the data and the accuracy of the data analysis, and approved the final version of the manuscript.
SUPPLEMENTARY MATERIAL The Supplementary Material for this article can be found online at: https://www.frontiersin.org/articles/10.3389/fmed. 2021.629176/full#supplementary-material
Conflict of Interest: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
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'abstract': '<jats:p><jats:bold>Purpose:</jats:bold> On the basis that spironolactone is involved in ACE2 '
'expression and TMPRSS2 activity, previous studies have suggested that spironolactone may '
'influence the infectivity of COVID-19. Research has suggested that cell entry of SARS-CoV-2, '
'the virus that induces COVID-19, is associated with the ACE2 receptor and TMPRSS2. The '
'purpose of this study was to investigate whether spironolactone has a protective effect '
'against COVID-19 and the development of associated complications in patients with liver '
'cirrhosis.</jats:p><jats:p><jats:bold>Methods:</jats:bold> We conducted a nationwide '
'case-control study on liver cirrhosis patients with or without COVID-19 from the '
'population-based data acquired from the National Health Insurance Systems of Republic of '
'Korea. After 1:5 case-control matching, multivariable adjusted conditional logistic '
'regression analysis was performed.</jats:p><jats:p><jats:bold>Results:</jats:bold> Among the '
'patients with liver cirrhosis, the case group with COVID-19 was found to be significantly '
'less exposed to spironolactone compared with the control group without COVID-19. The adjusted '
'odds ratio (OR) and 95% confidence interval (CI) between the two groups was 0.20 (0.07–0.54). '
'In addition, regardless of cumulative dose of spironolactone, exposure to spironolactone was '
'associated with lower COVID-19 infection. In terms of the development of complications due to '
'COVID-19, spironolactone did not show any significant association between the patients with '
'and without complications (<jats:italic>P</jats:italic> = 0.43). The adjusted OR and 95% CI '
'between the two groups was 1.714 '
'(0.246–11.938).</jats:p><jats:p><jats:bold>Conclusion:</jats:bold> We conclude that '
'spironolactone may reduce susceptibility to COVID-19 but does not affect the development of '
'its associated complications; however, further studies are needed to confirm the exact '
'association between spironolactone and COVID-19 infection.</jats:p>',
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