{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,19]],"date-time":"2026-02-19T00:07:16Z","timestamp":1771459636393,"version":"3.50.1"},"reference-count":58,"publisher":"MDPI AG","issue":"18","license":[{"start":{"date-parts":[[2023,9,18]],"date-time":"2023-09-18T00:00:00Z","timestamp":1694995200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Polish Medical Research Agency (ABM)","award":["2020.ABM.COVID19.0024"],"award-info":[{"award-number":["2020.ABM.COVID19.0024"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>In March 2020, the World Health Organization (WHO) announced a global pandemic of coronavirus disease 2019 (COVID-19) that presented mainly as an acute infection of the lower respiratory tract (pneumonia), with multiple long-term consequences, including lung fibrosis. The aim of this study was to evaluate the influence of potassium canrenoate on inflammatory markers in the treatment of COVID-19 pneumonia. A randomized clinical trial (RCT) of intravenous potassium canrenoate vs. placebo was performed between December 2020 and November 2021. This study is a secondary analysis of that RCT. In the final analysis, a total of 49 hospitalized patients were included (24 allocated to the potassium canrenoate group and 25 to the placebo group). Patients were assessed by serum testing and blood cell cytometry on day 1 and day 7 of the intervention. Age, sex, and body mass index were not significantly different between the placebo group and intervention group. Although there was a significantly higher rate of ischemic heart disease in the placebo group, rates of other preexisting comorbidities were not significantly different. There were no significant differences in the inflammatory parameters between the potassium canrenoate and placebo groups on day 1 and day 7. However, the intragroup comparisons using Wilcoxon\u2019s test showed significant differences between day 1 and day 7. The CD3% for potassium canrenoate increased significantly between day 1 and day 7 (12.85 \u00b1 9.46; 11.55 vs. 20.50 \u00b1 14.40; 17.80; p = 0.022), while the change in the placebo group was not significant (15.66 \u00b1 11.39; 12.65 vs. 21.16 \u00b1 15.37; 16.40; p = 0.181). The IL-1\u00df total count [%] increased over time for both potassium canrenoate (0.68 \u00b1 0.58; 0.45 vs. 1.27 \u00b1 0.83; 1.20; p = 0.004) and placebo (0.61 \u00b1 0.59; 0.40 vs. 1.16 \u00b1 0.91; 1.00; p = 0.016). The TNF-\u03b1 total count (%) decreased significantly between day 1 and day 7 for potassium canrenoate (0.54 \u00b1 0.45; 0.40 vs. 0.25 \u00b1 0.23; 0.10; p = 0.031), but not for placebo (0.53 \u00b1 0.47; 0.35 vs. 0.26 \u00b1 0.31; 0.20; p = 0.056). Interleukin-6 (pg\/mL) showed a significant decrease between day 1 and day 7 for potassium canrenoate (64.97 \u00b1 72.52; 41.00 vs. 24.20 \u00b1 69.38; 5.30; p = 0.006), but not the placebo group. This RCT has shown that the administration of potassium canrenoate to patients with COVID-19-induced pneumonia may be associated with significant changes in certain inflammatory markers (interleukin-6, CD3%, TNF-\u03b1), potentially related to pulmonary fibrosis. Although some positive trends were observed in the potassium canrenoate group, none of these observations reached statistical significance. Any possible benefits from the use of potassium canrenoate as an anti-inflammatory or antifibrotic drug in COVID-19 patients require further investigation.<\/jats:p>","DOI":"10.3390\/ijms241814247","type":"journal-article","created":{"date-parts":[[2023,9,19]],"date-time":"2023-09-19T02:26:17Z","timestamp":1695090377000},"page":"14247","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["The Effect of Potassium Canrenoate (Mineralocorticoid Receptor Antagonist) on the Markers of Inflammation in the Treatment of COVID-19 Pneumonia and Fibrosis\u2014A Secondary Analysis of Randomized Placebo-Controlled Clinical Trial"],"prefix":"10.3390","volume":"24","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8049-0833","authenticated-orcid":false,"given":"Igor","family":"Karolak","sequence":"first","affiliation":[{"name":"Department of Anesthesiology, Intensive Therapy and Acute Intoxications, Pomeranian Medical University in Szczecin, 70-111 Szczecin, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0688-6928","authenticated-orcid":false,"given":"Rafa\u0142","family":"Hrynkiewicz","sequence":"additional","affiliation":[{"name":"Institute of Biology, University of Szczecin, 71-412 Szczecin, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4065-3842","authenticated-orcid":false,"given":"Paulina","family":"Nied\u017awiedzka-Rystwej","sequence":"additional","affiliation":[{"name":"Institute of Biology, University of Szczecin, 71-412 Szczecin, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0807-8510","authenticated-orcid":false,"given":"Kacper","family":"Lechowicz","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology, Intensive Therapy and Acute Intoxications, Pomeranian Medical University in Szczecin, 70-111 Szczecin, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8141-7489","authenticated-orcid":false,"given":"Jerzy","family":"Sie\u0144ko","sequence":"additional","affiliation":[{"name":"Institute of Physical Culture Sciences, University of Szczecin, 70-453 Szczecin, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6105-5329","authenticated-orcid":false,"given":"Aleksandra","family":"Szyli\u0144ska","sequence":"additional","affiliation":[{"name":"Department of Medical Rehabilitation and Clinical Physiotherapy, Pomeranian Medical University in Szczecin, 71-210 Szczecin, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0449-2375","authenticated-orcid":false,"given":"Wojciech","family":"Dabrowski","sequence":"additional","affiliation":[{"name":"Department of Anaesthesiology, Intensive Care Medical University of Lublin, 20-059 Lublin, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8430-1369","authenticated-orcid":false,"given":"Katarzyna","family":"Kotfis","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology, Intensive Therapy and Acute Intoxications, Pomeranian Medical University in Szczecin, 70-111 Szczecin, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2023,9,18]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1061","DOI":"10.1001\/jama.2020.1585","article-title":"Clinical Characteristics of 138 Hospitalized Patients with 2019 Novel Coronavirus\u2013Infected Pneumonia in Wuhan, China","volume":"323","author":"Wang","year":"2020","journal-title":"JAMA"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"507","DOI":"10.1016\/S0140-6736(20)30211-7","article-title":"Epidemiological and Clinical Characteristics of 99 Cases of 2019 Novel Coronavirus Pneumonia in Wuhan, China: A Descriptive Study","volume":"395","author":"Chen","year":"2020","journal-title":"Lancet"},{"key":"ref_3","first-page":"312","article-title":"Triage during the COVID-19 Pandemic","volume":"52","author":"Damps","year":"2021","journal-title":"Anaesthesiol. Intensive Ther."},{"key":"ref_4","unstructured":"World Health Organization (2022, January 06). WHO Coronavirus (COVID-19) Dashboard. Available online: https:\/\/covid19.who.int."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"564","DOI":"10.1111\/irv.12758","article-title":"Epidemiological, Clinical, and Virological Characteristics of 465 Hospitalized Cases of Coronavirus Disease 2019 (COVID-19) from Zhejiang Province in China","volume":"14","author":"Lian","year":"2020","journal-title":"Influenza Other Respi. Viruses"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"132","DOI":"10.5114\/ait.2020.95164","article-title":"COVID-19: What Do We Need to Know About ICU Delirium during the SARS-CoV-2 Pandemic?","volume":"52","author":"Kotfis","year":"2020","journal-title":"Anaesthesiol. Intensive Ther."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"220","DOI":"10.1016\/S0140-6736(20)32656-8","article-title":"6-Month Consequences of COVID-19 in Patients Discharged from Hospital: A Cohort Study","volume":"397","author":"Huang","year":"2021","journal-title":"Lancet"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"250","DOI":"10.1002\/jmv.26232","article-title":"The Cytokine Storm and COVID-19","volume":"93","author":"Hu","year":"2021","journal-title":"J. Med. Virol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1033","DOI":"10.1016\/S0140-6736(20)30628-0","article-title":"COVID-19: Consider Cytokine Storm Syndromes and Immunosuppression","volume":"395","author":"Mehta","year":"2020","journal-title":"Lancet"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"102567","DOI":"10.1016\/j.autrev.2020.102567","article-title":"Should We Stimulate or Suppress Immune Responses in COVID-19? Cytokine and Anti-Cytokine Interventions","volume":"19","author":"Jamilloux","year":"2020","journal-title":"Autoimmun. Rev."},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Takahashi, T., Wong, P., Ellingson, M., Lucas, C., Klein, J., Israelow, B., Silva, J., Oh, J., Mao, T., and Tokuyama, M. (2020). Sex Differences in Immune Responses to SARS-CoV-2 That Underlie Disease Outcomes. medRxiv, Update in: Nature2020, 588, 315\u2013320.","DOI":"10.1101\/2020.06.06.20123414"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"38","DOI":"10.1016\/j.cytogfr.2020.04.002","article-title":"Cytokine Storm Intervention in the Early Stages of COVID-19 Pneumonia","volume":"53","author":"Sun","year":"2020","journal-title":"Cytokine Growth Factor Rev."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"679","DOI":"10.1089\/vim.2021.0071","article-title":"Interleukin-1 in COVID-19 Infection: Immunopathogenesis and Possible Therapeutic Perspective","volume":"34","author":"Mardi","year":"2021","journal-title":"Viral Immunol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1016\/j.it.2020.10.012","article-title":"A Potential Role of Interleukin 10 in COVID-19 Pathogenesis","volume":"42","author":"Lu","year":"2021","journal-title":"Trends Immunol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"105295","DOI":"10.1016\/j.psyneuen.2021.105295","article-title":"Interleukin-6 as Potential Mediator of Long-Term Neuropsychiatric Symptoms of COVID-19","volume":"131","author":"Kappelmann","year":"2021","journal-title":"Psychoneuroendocrinology"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"110112","DOI":"10.1016\/j.mehy.2020.110112","article-title":"Spironolactone May Provide Protection from SARS-CoV-2: Targeting Androgens, Angiotensin Converting Enzyme 2 (ACE2), and Renin-Angiotensin-Aldosterone System (RAAS)","volume":"143","author":"Cadegiani","year":"2020","journal-title":"Med. Hypotheses"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"422","DOI":"10.1186\/s13054-020-03120-0","article-title":"Role of Angiotensin-Converting Enzyme 2 (ACE2) in COVID-19","volume":"24","author":"Ni","year":"2020","journal-title":"Crit. Care"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"288","DOI":"10.1002\/path.2067","article-title":"Expression of Elevated Levels of Pro-Inflammatory Cytokines in SARS-CoV-Infected ACE2+ Cells in SARS Patients: Relation to the Acute Lung Injury and Pathogenesis of SARS","volume":"210","author":"He","year":"2006","journal-title":"J. Pathol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"7703","DOI":"10.1128\/JVI.02560-09","article-title":"Upregulation of the Chemokine (C-C Motif) Ligand 2 via a Severe Acute Respiratory Syndrome Coronavirus Spike-ACE2 Signaling Pathway","volume":"84","author":"Chen","year":"2010","journal-title":"J. Virol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"7602","DOI":"10.4049\/jimmunol.173.12.7602","article-title":"Induction of IL-8 Release in Lung Cells via Activator Protein-1 by Recombinant Baculovirus Displaying Severe Acute Respiratory Syndrome-Coronavirus Spike Proteins: Identification of Two Functional Regions","volume":"173","author":"Chang","year":"2004","journal-title":"J. Immunol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1042","DOI":"10.1038\/sj.bjp.0707454","article-title":"Angiotensin AT1 Receptor Antagonists Exert Anti-Inflammatory Effects in Spontaneously Hypertensive Rats","volume":"152","author":"Dai","year":"2007","journal-title":"Br. J. Pharmacol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"206","DOI":"10.3389\/fped.2020.00206","article-title":"COVID-19 Infection and Circulating ACE2 Levels: Protective Role in Women and Children","volume":"8","author":"Ciaglia","year":"2020","journal-title":"Front. Pediatr."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"2166","DOI":"10.1016\/j.lfs.2005.09.038","article-title":"Age- and Gender-Related Difference of ACE2 Expression in Rat Lung","volume":"78","author":"Xie","year":"2006","journal-title":"Life Sci."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"344","DOI":"10.1093\/clinchem\/36.2.344","article-title":"Serum Angiotensin-Converting Enzyme in Healthy and Sarcoidotic Children: Comparison with the Reference Interval for Adults","volume":"36","author":"Baudin","year":"1990","journal-title":"Clin. Chem."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"e4154","DOI":"10.1093\/cid\/ciaa1911","article-title":"Distinct Disease Severity Between Children and Older Adults With Coronavirus Disease 2019 (COVID-19): Impacts of ACE2 Expression, Distribution, and Lung Progenitor Cells","volume":"73","author":"Zhang","year":"2021","journal-title":"Clin. Infect. Dis."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"108588","DOI":"10.1016\/j.clim.2020.108588","article-title":"SARS-CoV-2 Infections in Children and Young People","volume":"220","author":"Felsenstein","year":"2020","journal-title":"Clin. Immunol."},{"key":"ref_27","first-page":"87","article-title":"The Impact of Spironolactone on the Lung Injury Induced By Concomitant Trastuzumab and Thoracic Radiotherapy","volume":"17","author":"Yavas","year":"2019","journal-title":"Int. J. Radiat. Res."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"2401","DOI":"10.2147\/JIR.S409146","article-title":"The Correlation Between Aldosterone and Leukocyte-Related Inflammation: A Comparison Between Patients with Primary Aldosteronism and Essential Hypertension","volume":"16","author":"Rao","year":"2023","journal-title":"J. Inflamm. Res."},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Kotfis, K., Lechowicz, K., Dro\u017cd\u017cal, S., Nied\u017awiedzka-Rystwej, P., Wojdacz, T.K., Grywalska, E., Biernawska, J., Wi\u015bniewska, M., and Parczewski, M. (2021). COVID-19\u2014The Potential Beneficial Therapeutic Effects of Spironolactone during SARS-CoV-2 Infection. Pharmaceuticals, 14.","DOI":"10.3390\/ph14010071"},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Kumar, N., Zuo, Y., Yalavarthi, S., Hunker, K.L., Knight, J.S., Kanthi, Y., Obi, A.T., and Ganesh, S.K. (2021). SARS-CoV-2 Spike Protein S1-Mediated Endothelial Injury and Pro-Inflammatory State Is Amplified by Dihydrotestosterone and Prevented by Mineralocorticoid Antagonism. Viruses, 13.","DOI":"10.3390\/v13112209"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"323","DOI":"10.1097\/FJC.0000000000000960","article-title":"Is Spironolactone the Preferred Renin\u2013Angiotensin\u2013Aldosterone Inhibitor for Protection Against COVID-19?","volume":"77","author":"Wilcox","year":"2021","journal-title":"J. Cardiovasc. Pharmacol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"290","DOI":"10.1016\/j.ejphar.2013.08.019","article-title":"Mineralocorticoid Receptor Antagonists Attenuate Pulmonary Inflammation and Bleomycin-Evoked Fibrosis in Rodent Models","volume":"718","author":"Lieber","year":"2013","journal-title":"Eur. J. Pharmacol."},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Ji, W.-J., Ma, Y.-Q., Zhou, X., Zhang, Y.-D., Lu, R.-Y., Guo, Z.-Z., Sun, H.-Y., Hu, D.-C., Yang, G.-H., and Li, Y.-M. (2013). Spironolactone Attenuates Bleomycin-Induced Pulmonary Injury Partially via Modulating Mononuclear Phagocyte Phenotype Switching in Circulating and Alveolar Compartments. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0081090"},{"key":"ref_34","first-page":"501","article-title":"The Efficacy of Spironolactone in the Treatment of Acute Respiratory Distress Syndrome-Induced Rats","volume":"51","author":"Atalay","year":"2010","journal-title":"Singap. Med. J."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"15","DOI":"10.25011\/cim.v39i1.26326","article-title":"Reduction of Acute Lung Injury by Administration of Spironolactone After Intestinal Ischemia and Reperfusion in Rats","volume":"39","author":"Barut","year":"2016","journal-title":"Clin. Investig. Med."},{"key":"ref_36","first-page":"415","article-title":"Comparative Evaluation of Inhaling a Single Dose of Furosemide or Spironolactone on Bronchial Hyperreactivity of Patients with Atopic Bronchial Asthma","volume":"49","author":"Maleszka","year":"1994","journal-title":"Pol. Tyg. Lek."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"T125","DOI":"10.1530\/JOE-16-0600","article-title":"30 YEARS OF THE MINERALOCORTICOID RECEPTOR: Mineralocorticoid Receptor Antagonists: 60 Years of Research and Development","volume":"234","author":"Kolkhof","year":"2017","journal-title":"J. Endocrinol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"1917","DOI":"10.1210\/js.2019-00158","article-title":"Glucocorticoid and Mineralocorticoid Receptors in the Brain: A Transcriptional Perspective","volume":"3","author":"Koning","year":"2019","journal-title":"J. Endocr. Soc."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"299","DOI":"10.1016\/j.mce.2011.06.020","article-title":"Mineralocorticoid and Glucocorticoid Receptors at the Neuronal Membrane, Regulators of Nongenomic Corticosteroid Signalling","volume":"350","author":"Groeneweg","year":"2012","journal-title":"Mol. Cell. Endocrinol."},{"key":"ref_40","doi-asserted-by":"crossref","unstructured":"Zou, J.-N., Sun, L., Wang, B.-R., Zou, Y., Xu, S., Ding, Y.-J., Shen, L.-J., Huang, W.-C., Jiang, X.-J., and Chen, S.-M. (2021). The characteristics and evolution of pulmonary fibrosis in COVID-19 patients as assessed by AI-assisted chest HRCT. PLoS ONE, 16.","DOI":"10.1371\/journal.pone.0248957"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"452","DOI":"10.1016\/j.jinf.2020.06.008","article-title":"Interleukin-6 as prognosticator in patients with COVID-19","volume":"81","author":"Grifoni","year":"2020","journal-title":"J. Infect."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"1491","DOI":"10.1056\/NEJMoa2100433","article-title":"Interleukin-6 Receptor Antagonists in Critically Ill Patients with COVID-19","volume":"384","author":"Gordon","year":"2021","journal-title":"N. Engl. J. Med."},{"key":"ref_43","doi-asserted-by":"crossref","unstructured":"Lechowicz, K., Dro\u017cd\u017cal, S., Machaj, F., Rosik, J., Szostak, B., Zegan-Bara\u0144ska, M., Biernawska, J., Dabrowski, W., Rotter, I., and Kotfis, K. (2020). COVID-19: The Potential Treatment of Pulmonary Fibrosis Associated with SARS-CoV-2 Infection. J. Clin. Med., 9.","DOI":"10.3390\/jcm9061917"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"746","DOI":"10.3348\/kjr.2020.0215","article-title":"Prediction of the Development of Pulmonary Fibrosis Using Serial Thin-Section Ct and Clinical Features in Patients Discharged after Treatment for COVID-19 Pneumonia","volume":"21","author":"Yu","year":"2020","journal-title":"Korean J. Radiol."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"1339","DOI":"10.1084\/jem.20110551","article-title":"Integrating Mechanisms of Pulmonary Fibrosis","volume":"208","author":"Wynn","year":"2011","journal-title":"J. Exp. Med."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"897","DOI":"10.1177\/1535370220915428","article-title":"IL-25\/IL-33\/TSLP Contributes to Idiopathic Pulmonary Fibrosis: Do Alveolar Epithelial Cells and (Myo)Fibroblasts Matter?","volume":"245","author":"Xu","year":"2020","journal-title":"Exp. Biol. Med."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"L715","DOI":"10.1152\/ajplung.00361.2009","article-title":"Epithelial Repair Mechanisms in the Lung","volume":"298","author":"Crosby","year":"2010","journal-title":"Am. J. Physiol. Lung Cell. Mol. Physiol."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"2173","DOI":"10.2147\/JIR.S406658","article-title":"The Diagnostic Value of Inflammatory Markers (CRP, IL6, CRP\/IL6, CRP\/L, LCR) for Assessing the Severity of COVID-19 Symptoms Based on the MEWS and Predicting the Risk of Mortality","volume":"16","author":"Dorf","year":"2023","journal-title":"J. Inflamm. Res."},{"key":"ref_49","first-page":"e22770","article-title":"Post-COVID-19 Pulmonary Fibrosis","volume":"14","author":"Mohammadi","year":"2022","journal-title":"Cureus"},{"key":"ref_50","doi-asserted-by":"crossref","unstructured":"Jover, E., Matilla, L., Garaikoetxea, M., Fern\u00e1ndez-Celis, A., Muntendam, P., Jaisser, F., Rossignol, P., and L\u00f3pez-Andr\u00e9s, N. (2021). Beneficial Effects of Mineralocorticoid Receptor Pathway Blockade against Endothelial Inflammation Induced by Sars-COV-2 Spike Protein. Biomedicines, 9.","DOI":"10.3390\/biomedicines9060639"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"1069","DOI":"10.1007\/s00424-022-02726-3","article-title":"Mineralocorticoid Receptor-Antagonism Prevents COVID-19-Dependent Glycocalyx Damage","volume":"474","author":"Fels","year":"2022","journal-title":"Pflug. Arch."},{"key":"ref_52","first-page":"4","article-title":"Results of Open-Label Non-Randomized Comparative Clinical Trial: \u201cBromhexine and Spironolactone for Coronavirus Infection Requiring Hospitalization (BISCUIT)","volume":"60","author":"Mareev","year":"2020","journal-title":"Kardiologiya"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"454","DOI":"10.1016\/j.ijid.2021.05.055","article-title":"Efficacy and Safety of Nintedanib for Pulmonary Fibrosis in Severe Pneumonia Induced by COVID-19: An Interventional Study","volume":"108","author":"Umemura","year":"2021","journal-title":"Int. J. Infect. Dis."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"2001808","DOI":"10.1183\/13993003.01808-2020","article-title":"Rapid Onset Honeycombing Fibrosis in Spontaneously Breathing Patient with COVID-19","volume":"56","author":"Combet","year":"2020","journal-title":"Eur. Respir. J."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"e01041","DOI":"10.1016\/j.idcr.2020.e01041","article-title":"Post COVID-19 fibrosis, an emerging complicationof SARS-CoV-2 infection","volume":"23","author":"Alhiyari","year":"2021","journal-title":"IDCases"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"502","DOI":"10.1186\/s13054-020-03220-x","article-title":"Auxora versus Standard of Care for the Treatment of Severe or Critical COVID-19 Pneumonia: Results from a Randomized Controlled Trial","volume":"24","author":"Miller","year":"2020","journal-title":"Crit. Care"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"629176","DOI":"10.3389\/fmed.2021.629176","article-title":"Effect of Spironolactone on COVID-19 in Patients With Underlying Liver Cirrhosis: A Nationwide Case-Control Study in South Korea","volume":"8","author":"Jeon","year":"2021","journal-title":"Front. Med."},{"key":"ref_58","doi-asserted-by":"crossref","unstructured":"Wadhwa, B., Malhotra, V., Kerai, S., Husain, F., Pandey, N.B., Saxena, K.N., Singh, V., Quinn, T.M., Li, F., and Gaughan, E. (2023). Phase 2 randomised placebo-controlled trial of spironolactone and dexamethasone versus dexamethasone in COVID-19 hospitalised patients in Delhi. BMC Infect. Dis., 23.","DOI":"10.1186\/s12879-023-08286-w"}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/24\/18\/14247\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T20:53:13Z","timestamp":1760129593000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/24\/18\/14247"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,9,18]]},"references-count":58,"journal-issue":{"issue":"18","published-online":{"date-parts":[[2023,9]]}},"alternative-id":["ijms241814247"],"URL":"https:\/\/doi.org\/10.3390\/ijms241814247","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,9,18]]}}}