Results of Open-Label non-Randomized Comparative Clinical Trial: “BromhexIne and Spironolactone for CoronаvirUs Infection requiring hospiTalization (BISCUIT)

{ 'indexed': {'date-parts': [[2024, 1, 9]], 'date-time': '2024-01-09T20:13:22Z', 'timestamp': 1704831202976}, 'reference-count': 42, 'publisher': 'APO Society of Specialists in Heart Failure', 'issue': '11', 'license': [ { 'start': { 'date-parts': [[2020, 12, 3]], 'date-time': '2020-12-03T00:00:00Z', 'timestamp': 1606953600000}, 'content-version': 'vor', 'delay-in-days': 0, 'URL': 'https://lib.ossn.ru/jour/about/editorialPolicies#openAccessPolicy'}], 'content-domain': {'domain': [], 'crossmark-restriction': False}, 'abstract': '<jats:p><jats:italic>Introduction</jats:italic> The aim of this study was to assess the ' 'efficacy and safety of a combination of bromhexine at a dose of 8 mg 4 times a day and ' 'spironolactone 50 mg per day in patients with mild and moderate COVID ' '19.<jats:italic>Material and methods</jats:italic> It was an open, prospective comparative ' 'non-randomized study. 103 patients were included (33 in the bromhexine and spironolactone ' 'group and 70 in the control group). All patients had a confirmed 2019 novel coronavirus ' 'infection (COVID 19) based on a positive polymerase chain reaction (PCR) for SARS-CoV-2 virus ' 'RNA and/or a typical pattern of viral pneumonia on multispiral computed tomography. The ' 'severity of lung damage was limited to stage I-II, the level of CRP should not exceed 60 mg / ' 'dL and SO2 in the air within 92-98%. The duration of treatment is 10 ' 'days.<jats:italic>Results</jats:italic> The decrease in scores on the SHOKS-COVID scale, ' 'which, in addition to assessing the clinical status, the dynamics of CRP (a marker of ' 'inflammation), D-dimer (a marker of thrombus formation), and the degree of lung damage on CT ' '(primary endpoint) was statistically significant in both groups and differences between them ' 'was not identified. Analysis for the group as a whole revealed a statistically significant ' 'reduction in hospitalization time from 10.4 to 9.0 days (by 1.5 days, p=0.033) and fever time ' 'from 6.5 to 3.9 days (by 2.5 days, p&lt;0.001). Given the incomplete balance of the groups, ' 'the main analysis included 66 patients who were match with using propensity score matching. ' 'In matched patients, temperature normalization in the bromhexine/spironolactone group ' 'occurred 2 days faster than in the control group (p=0.008). Virus elimination by the 10th day ' 'was recorded in all patients in the bromhexine/spironolactone group; the control group ' 'viremia continued in 23.3% (p=0.077). The number of patients who had a positive PCR to the ' 'SARS-CoV-2 virus on the 10th day of hospitalization or longer (≥10 days) hospitalization in ' 'the control group was 20/21 (95.2%), and in the group with bromhexine /spironolactone -14/24 ' '(58.3%), p=0.012. The odds ratio of having a positive PCR or more than ten days of ' 'hospitalization was 0.07 (95% CI: 0.008 - 0.61, p=0.0161) with bromhexine and spironolactone ' 'versus controls. No side effects were reported in the study ' 'group.<jats:italic>Conclusion</jats:italic> The combination of bromhexine with spironolactone ' 'appeared effective in treating a new coronavirus infection by achieving a faster ' 'normalization of the clinical condition, lowering the temperature one and a half times ' 'faster, and reducing explanatory combine endpoint the viral load or long duration of ' 'hospitalization (≥ 10 days).</jats:p>', 'DOI': '10.18087/cardio.2020.11.n1440', 'type': 'journal-article', 'created': {'date-parts': [[2021, 1, 25]], 'date-time': '2021-01-25T08:30:07Z', 'timestamp': 1611563407000}, 'page': '4-15', 'source': 'Crossref', 'is-referenced-by-count': 16, 'title': 'Results of Open-Label non-Randomized Comparative Clinical Trial: “BromhexIne and Spironolactone ' 'for CoronаvirUs Infection requiring hospiTalization (BISCUIT)', 'prefix': '10.18087', 'volume': '60', 'author': [ { 'ORCID': 'http://orcid.org/0000-0002-7285-2048', 'authenticated-orcid': True, 'given': 'V. Yu.', 'family': 'Mareev', 'sequence': 'first', 'affiliation': [ { 'name': 'Medical Research and Educational Center of the M. V. Lomonosov ' 'Moscow State University, Moscow, Russia\r\n' 'Faculty of Fundamental Medicine, Lomonosov Moscow State ' 'University, Russia'}]}, { 'ORCID': 'http://orcid.org/0000-0002-8160-5612', 'authenticated-orcid': True, 'given': 'Ya. A.', 'family': 'Orlova', 'sequence': 'additional', 'affiliation': [ { 'name': 'Medical Research and Educational Center of the M. V. Lomonosov ' 'Moscow State University, Moscow, Russia\r\n' 'Faculty of Fundamental Medicine, Lomonosov Moscow State ' 'University, Russia'}]}, { 'given': 'A. G.', 'family': 'Plisyk', 'sequence': 'additional', 'affiliation': [ { 'name': 'Medical Research and Educational Center of the M. V. Lomonosov ' 'Moscow State University, Moscow, Russia\r\n' 'Faculty of Fundamental Medicine, Lomonosov Moscow State ' 'University, Russia'}]}, { 'ORCID': 'http://orcid.org/0000-0001-7693-5281', 'authenticated-orcid': True, 'given': 'E. P.', 'family': 'Pavlikova', 'sequence': 'additional', 'affiliation': [ { 'name': 'Medical Research and Educational Center of the M. V. Lomonosov ' 'Moscow State University, Moscow, Russia\r\n' 'Faculty of Fundamental Medicine, Lomonosov Moscow State ' 'University, Russia'}]}, { 'ORCID': 'http://orcid.org/0000-0002-5670-167X', 'authenticated-orcid': True, 'given': 'S. T.', 'family': 'Matskeplishvili', 'sequence': 'additional', 'affiliation': [ { 'name': 'Medical Research and Educational Center of the M. V. Lomonosov ' 'Moscow State University, Moscow, Russia'}]}, { 'given': 'Z. A.', 'family': 'Akopyan', 'sequence': 'additional', 'affiliation': [ { 'name': 'Medical Research and Educational Center of the M. V. Lomonosov ' 'Moscow State University, Moscow, Russia\r\n' 'Faculty of Fundamental Medicine, Lomonosov Moscow State ' 'University, Russia'}]}, { 'ORCID': 'http://orcid.org/0000-0002-1490-2078', 'authenticated-orcid': True, 'given': 'E. M.', 'family': 'Seredenina', 'sequence': 'additional', 'affiliation': [ { 'name': 'Medical Research and Educational Center of the M. V. Lomonosov ' 'Moscow State University, Moscow, Russia\r\n' 'Faculty of Fundamental Medicine, Lomonosov Moscow State ' 'University, Russia'}]}, { 'ORCID': 'http://orcid.org/0000-0002-9820-4276', 'authenticated-orcid': True, 'given': 'A. V.', 'family': 'Potapenko', 'sequence': 'additional', 'affiliation': [ { 'name': 'Medical Research and Educational Center of the M. V. Lomonosov ' 'Moscow State University, Moscow, Russia\r\n' 'Faculty of Fundamental Medicine, Lomonosov Moscow State ' 'University, Russia'}]}, { 'given': 'M. A.', 'family': 'Agapov', 'sequence': 'additional', 'affiliation': [ { 'name': 'Medical Research and Educational Center of the M. V. Lomonosov ' 'Moscow State University, Moscow, Russia\r\n' 'Faculty of Fundamental Medicine, Lomonosov Moscow State ' 'University, Russia'}]}, { 'ORCID': 'http://orcid.org/0000-0002-1939-7189', 'authenticated-orcid': True, 'given': 'D. A.', 'family': 'Asratyan', 'sequence': 'additional', 'affiliation': [ { 'name': 'Medical Research and Educational Center of the M. V. Lomonosov ' 'Moscow State University, Moscow, Russia'}]}, { 'given': 'L. I.', 'family': 'Dyachuk', 'sequence': 'additional', 'affiliation': [ { 'name': 'Medical Research and Educational Center of the M. V. Lomonosov ' 'Moscow State University, Moscow, Russia\r\n' 'Faculty of Fundamental Medicine, Lomonosov Moscow State ' 'University, Russia'}]}, { 'ORCID': 'http://orcid.org/0000-0001-6734-3989', 'authenticated-orcid': True, 'given': 'L. M.', 'family': 'Samokhodskaya', 'sequence': 'additional', 'affiliation': [ { 'name': 'Medical Research and Educational Center of the M. V. Lomonosov ' 'Moscow State University, Moscow, Russia\r\n' 'Faculty of Fundamental Medicine, Lomonosov Moscow State ' 'University, Russia'}]}, { 'ORCID': 'http://orcid.org/0000-0002-1266-4926', 'authenticated-orcid': True, 'given': 'Е. А.', 'family': 'Mershina', 'sequence': 'additional', 'affiliation': [ { 'name': 'Medical Research and Educational Center of the M. V. Lomonosov ' 'Moscow State University, Moscow, Russia\r\n' 'Faculty of Fundamental Medicine, Lomonosov Moscow State ' 'University, Russia'}]}, { 'ORCID': 'http://orcid.org/0000-0002-5649-2193', 'authenticated-orcid': True, 'given': 'V. E.', 'family': 'Sinitsyn', 'sequence': 'additional', 'affiliation': [ { 'name': 'Medical Research and Educational Center of the M. V. Lomonosov ' 'Moscow State University, Moscow, Russia\r\n' 'Faculty of Fundamental Medicine, Lomonosov Moscow State ' 'University, Russia'}]}, { 'given': 'P. V.', 'family': 'Pakhomov', 'sequence': 'additional', 'affiliation': [ { 'name': 'Faculty of Fundamental Medicine, Lomonosov Moscow State ' 'University, Russia'}]}, { 'given': 'M. M.', 'family': 'Bulanova', 'sequence': 'additional', 'affiliation': [ { 'name': 'Faculty of Fundamental Medicine, Lomonosov Moscow State ' 'University, Russia'}]}, { 'given': 'A. A.', 'family': 'Fuks', 'sequence': 'additional', 'affiliation': [ { 'name': 'Faculty of Fundamental Medicine, Lomonosov Moscow State ' 'University, Russia'}]}, { 'ORCID': 'http://orcid.org/0000-0002-1939-7189', 'authenticated-orcid': True, 'given': 'Yu. V.', 'family': 'Mareev', 'sequence': 'additional', 'affiliation': [ { 'name': 'National Medical Research Centre for Therapy and Preventive ' 'Medicine, Moscow, Russia\r\n' 'Robertson Centre for Biostatistics, Glasgow, Great Britain'}]}, { 'ORCID': 'http://orcid.org/0000-0001-7992-6081', 'authenticated-orcid': True, 'given': 'Yu. L.', 'family': 'Begrambekova', 'sequence': 'additional', 'affiliation': [ { 'name': 'Medical Research and Educational Center of the M. V. Lomonosov ' 'Moscow State University, Moscow, Russia\r\n' 'Faculty of Fundamental Medicine, Lomonosov Moscow State ' 'University, Russia'}]}, { 'ORCID': 'http://orcid.org/0000-0003-4251-7545', 'authenticated-orcid': True, 'given': 'А. А.', 'family': 'Kamalov', 'sequence': 'additional', 'affiliation': [ { 'name': 'Medical Research and Educational Center of the M. V. Lomonosov ' 'Moscow State University, Moscow, Russia\r\n' 'Faculty of Fundamental Medicine, Lomonosov Moscow State ' 'University, Russia'}]}], 'member': '7442', 'published-online': {'date-parts': [[2020, 12, 3]]}, 'reference': [ { 'key': 'ref1', 'doi-asserted-by': 'crossref', 'unstructured': 'Cao B, Wang Y, Wen D, Liu W, Wang J, Fan G et al. A Trial of ' 'Lopinavir–Ritonavir in Adults Hospitalized with Severe Covid-19. New ' 'England Journal of Medicine. 2020;382(19):1787–99. DOI: ' '10.1056/NEJMoa2001282', 'DOI': '10.1056/NEJMc2008043'}, { 'key': 'ref2', 'doi-asserted-by': 'crossref', 'unstructured': 'Horby PW, Mafham M, Bell JL, Linsell L, Staplin N, Emberson J et al. ' 'Lopinavir–ritonavir in patients admitted to hospital with COVID-19 ' '(RECOVERY): a randomised, controlled, open-label, platform tr al. The ' 'Lancet. 2020;396(10259):1345–52. DOI: 10.1016/S0140-6736(20)32013-4', 'DOI': '10.1016/S0140-6736(20)32013-4'}, { 'key': 'ref3', 'doi-asserted-by': 'crossref', 'unstructured': 'Beigel JH, Tomashek KM, Dodd LE, Mehta AK, Zingman BS, Kalil AC et al. ' 'Remdesivir for the Treatment of Covid-19 — Preliminary Report. New ' 'England Journal of Medicine. 2020;NEJMoa2007764. [Epub ahead of print]. ' 'DOI: 10.1056/NEJMoa2007764', 'DOI': '10.1056/NEJMoa2007764'}, { 'key': 'ref4', 'doi-asserted-by': 'crossref', 'unstructured': 'Wang Y, Zhang D, Du G, Du R, Zhao J, Jin Y et al. Remdesivir in adults ' 'with severe COVID-19: a randomised, double-blind, placebo-controlled, ' 'multicentre trial. The Lancet. 2020;395(10236):1569–78. DOI: ' '10.1016/S0140-6736(20)31022-9', 'DOI': '10.1016/S0140-6736(20)31022-9'}, { 'key': 'ref5', 'doi-asserted-by': 'crossref', 'unstructured': 'Adamsick ML, Gandhi RG, Bidell MR, Elshaboury RH, Bhattacharyya RP, Kim ' 'AY et al. Remdesivir in Patients with Acute or Chronic Kidney Disease ' 'and COVID-19. Journal of the American Society of Nephrology. ' '2020;31(7):1384–6. DOI: 10.1681/ASN.2020050589', 'DOI': '10.1681/ASN.2020050589'}, { 'key': 'ref6', 'doi-asserted-by': 'crossref', 'unstructured': 'Fan Q, Zhang B, Ma J, Zhang S. Safety profile of the antiviral drug ' 'remdesivir: An update. Biomedicine & Pharmacotherapy. 2020;130:110532. ' 'DOI: 10.1016/j.biopha.2020.110532', 'DOI': '10.1016/j.biopha.2020.110532'}, { 'key': 'ref7', 'unstructured': 'Pharmaceutical technology. Fujifilm to seek approval for Avigan in ' 'Covid-19 after positive data. 23 September 2020. [Internet] Available ' 'at: ' 'https://www.pharmaceutical-technology.com/news/fujifilm-avigan-covid-data/#:~:text=Japan’s%20Fujifilm%20Toyama%20Chemical%20plans,in%20Japan%20to%20treat%20influenza'}, { 'key': 'ref8', 'unstructured': 'Medvestnik. RDIF announced the first results of the Favipiravir study ' 'for COVID-19 in Russia. 14.05.2020. Available at: ' 'https://medvestnik.ru/content/news/Bolee-polovinyprinimavshih-Favipiravir-uchastnikov-issledovanii-izlechilis-ot-koronavirusa.html'}, { 'key': 'ref9', 'unstructured': 'Ministry of Health of Russian Federation. Temporary methodical ' 'recommendations. Prevention, diagnosis and treatment of new coronavirus ' 'infection (COVID-2019). Version 9 (26.10.2020).'}, { 'key': 'ref10', 'unstructured': 'Av. at: ' 'https://static-.minzdrav.gov.ru/system/attachments/attaches/000/052/548/original/%D0%9C%D0%A0_COVID19_%28v.9%29.pdf?1603730062.'}, { 'key': 'ref11', 'doi-asserted-by': 'crossref', 'unstructured': 'Mareev V.Yu., Orlova Ya.A., Pavlikova E.P., Matskeplishvili S.T., ' 'Krasnova T.N., Malahov P.S. et al. Steroid pulse-therapy in patients ' 'With coronAvirus Pneumonia (COVID-19), sYstemic inFlammation And Risk of ' 'vEnous thRombosis and thromboembolism (WAYFARER Study). Kardiologiia. ' '2020;60(6):15–29. DOI: 10.18087/cardio.2020.6.n1226', 'DOI': '10.18087/cardio.2020.6.n1226'}, { 'key': 'ref12', 'doi-asserted-by': 'crossref', 'unstructured': 'Sonawane K, Barale SS, Dhanavade MJ, Waghmare SR, Nadaf NH, Kamble SA et ' 'al. Homology Modeling and Docking Studies of TMPRSS2 with Experimentally ' 'Known Inhibitors Camostat Mesylate, Nafamostat and Bromhexine ' 'Hydrochloride to Control SARS-Coronavirus-2. 2020. [Av. at: ' 'https://chemrxiv.org/articles/Homology_Modeling_and_Docking_Studies_of_TMPRSS2_with_Experimentally_Known_Inhibitors_Camostat_Mesylate_Nafamostat_and_Bromhexine_Hydrochloride_to_Control_SARS-Coronavirus-2/12162360/1].', 'DOI': '10.26434/chemrxiv.12162360'}, { 'key': 'ref13', 'doi-asserted-by': 'crossref', 'unstructured': 'Zanasi A, Mazzolini M, Kantar A. A reappraisal of the mucoactive ' 'activity and clinical efficacy of bromhexine. Multidisciplinary ' 'Respiratory Medicine. 2017;12(1):7. DOI: 10.1186/s40248-017-0088-1', 'DOI': '10.1186/s40248-017-0088-1'}, { 'key': 'ref14', 'doi-asserted-by': 'crossref', 'unstructured': 'Ji W-J, Ma Y-Q, Zhou X, Zhang Y-D, Lu R-Y, Guo Z-Z et al. Spironolactone ' 'Attenuates Bleomycin-Induced Pulmonary Injury Partially via Modulating ' 'Mononuclear Phagocyte Phenotype Switching in Circulating and Alveolar ' 'Compartments. PLoS ONE. 2013;8(11):e81090. DOI: ' '10.1371/journal.pone.0081090', 'DOI': '10.1371/journal.pone.0081090'}, { 'key': 'ref15', 'doi-asserted-by': 'crossref', 'unstructured': 'Wambier CG, Goren A, Ossimetha A, Nau G, Qureshi AA. Androgen-driven ' 'COVID-19 pandemic theory. ResearchGate. 2020; DOI: ' '10.13140/RG.2.2.21254.11848', 'DOI': '10.2139/ssrn.3571863'}, { 'key': 'ref16', 'doi-asserted-by': 'crossref', 'unstructured': 'Goren A, Vaño‐Galván S, Wambier CG, McCoy J, Gomez‐Zubiaur A, ' 'Moreno‐Arrones OM et al. A preliminary observation: Male pattern hair ' 'loss among hospitalized COVID‐19 patients in Spain – A potential clue to ' 'the role of androgens in COVID‐19 severity. Journal of Cosmetic ' 'Dermatology. 2020;19(7):1545–7. DOI: 10.1111/jocd.13443', 'DOI': '10.1111/jocd.13443'}, { 'key': 'ref17', 'doi-asserted-by': 'crossref', 'unstructured': 'Asselta R, Paraboschi EM, Mantovani A, Duga S. ACE2 and TMPRSS2 variants ' 'and expression as candidates to sex and country differences in COVID-19 ' 'severity in Italy. 2020. [Av. at: ' 'http://medrxiv.org/lookup/doi/10.1101/2020.03.30.20047878].', 'DOI': '10.1101/2020.03.30.20047878'}, { 'key': 'ref18', 'doi-asserted-by': 'crossref', 'unstructured': 'Mareev V.Yu., Orlova Ya.A., Pavlikova E.P., Matskeplishvili S.T., ' 'Akopyan Zh.A., Plisyk A.G. et al. Combination therapy at an early stage ' 'of the novel coronavirus infection (COVID-19). Case series and design of ' 'the clinical trial “BromhexIne and Spironolactone for CoronаvirUs ' 'Infection requiring hospiTalization (BISCUIT)”. Kardiologiia. ' '2020;60(8):4–15. DOI: 10.18087/cardio.2020.8.n1307', 'DOI': '10.18087/cardio.2020.8.n1307'}, { 'key': 'ref19', 'unstructured': 'Lomonosov Moscow State University Medical Research and Educational ' 'Center. Open Label Randomized Clinical Trial BromhexIne And ' 'Spironolactone For CoronаVirUs Infection Requiring HospiTalization. ' 'ClinicalTrials.gov Identifier: NCT04424134. 2020. [Av. at: ' 'https://clinicaltrials.gov/ct2/show/NCT04424134].'}, { 'key': 'ref20', 'unstructured': 'Royal College of Physicians. National Early Warning Score (NEWS) 2. [Av. ' 'at: ' 'https://www.rcplondon.ac.uk/projects/outputs/national-early-warning-score-news-2]. ' '2017.'}, { 'key': 'ref21', 'doi-asserted-by': 'crossref', 'unstructured': 'Liao X, Wang B, Kang Y. Novel coronavirus infection during the 2019–2020 ' 'epidemic: preparing intensive care units—the experience in Sichuan ' 'Province, China. Intensive Care Medicine. 2020;46(2):357–60. DOI: ' '10.1007/s00134-020-05954-2', 'DOI': '10.1007/s00134-020-05954-2'}, { 'key': 'ref22', 'doi-asserted-by': 'crossref', 'unstructured': 'Spinner CD, Gottlieb RL, Criner GJ, Arribas López JR, Cattelan AM, ' 'Soriano Viladomiu A et al. Effect of Remdesivir vs Standard Care on ' 'Clinical Status at 11 Days in Patients With Moderate COVID-19: A ' 'Randomized Clinical Trial. JAMA. 2020;324(11):1048. DOI: ' '10.1001/jama.2020.16349', 'DOI': '10.1001/jama.2020.16349'}, { 'key': 'ref23', 'doi-asserted-by': 'crossref', 'unstructured': 'Geleris J, Sun Y, Platt J, Zucker J, Baldwin M, Hripcsak G et al. ' 'Observational Study of Hydroxychloroquine in Hospitalized Patients with ' 'Covid-19. New England Journal of Medicine. 2020;382(25):2411–8. DOI: ' '10.1056/NEJMoa2012410', 'DOI': '10.1056/NEJMoa2012410'}, { 'key': 'ref24', 'doi-asserted-by': 'crossref', 'unstructured': 'Horby P, Mafham M, Linsell L, Bell JL, Staplin N, Emberson JR et al. ' 'Effect of Hydroxychloroquine in Hospitalized Patients with COVID-19: ' 'Preliminary results from a multi-centre, randomized, controlled trial. ' '2020. [Av. at: ' 'http://medrxiv.org/lookup/doi/10.1101/2020.07.15.20151852].', 'DOI': '10.1101/2020.07.15.20151852'}, { 'key': 'ref25', 'unstructured': 'WHO Solidarity trial consortium, Pan H, Peto R, Karim QA, Alejandria M, ' 'Henao-Restrepo AM et al. Repurposed antiviral drugs for COVID-19 ' '–interim WHO SOLIDARITY trial results. [Av. at: ' 'http://medrxiv.org/lookup/doi/10.1101/2020.10.15.20209817]. 2020.'}, { 'key': 'ref26', 'doi-asserted-by': 'crossref', 'unstructured': 'Sanders JM, Monogue ML, Jodlowski TZ, Cutrell JB. Pharmacologic ' 'Treatments for Coronavirus Disease 2019 (COVID- 19): A Review. JAMA. ' '2020;323(18):1824–36. DOI: 10.1001/jama.2020.6019', 'DOI': '10.1001/jama.2020.6019'}, { 'key': 'ref27', 'doi-asserted-by': 'crossref', 'unstructured': 'Cai Q, Yang M, Liu D, Chen J, Shu D, Xia J et al. Experimental Treatment ' 'with Favipiravir for COVID-19: An Open-Label Control Study. Engineering. ' '2020; [Epub ahead of print]. DOI: 10.1016/j.eng.2020.03.007', 'DOI': '10.1016/j.eng.2020.03.007'}, { 'key': 'ref28', 'doi-asserted-by': 'crossref', 'unstructured': 'Hung IF-N, Lung K-C, Tso EY-K, Liu R, Chung TW-H, Chu M-Y et al. Triple ' 'combination of interferon beta-1b, lopinavir–ritonavir, and ribavirin in ' 'the treatment of patients admitted to hospital with COVID-19: an ' 'open-label, randomised, phase 2 trial. The Lancet. ' '2020;395(10238):1695–704. DOI: 10.1016/S0140-6736(20)31042-4', 'DOI': '10.1016/S0140-6736(20)31042-4'}, { 'key': 'ref29', 'doi-asserted-by': 'crossref', 'unstructured': 'Shen LW, Mao HJ, Wu YL, Tanaka Y, Zhang W. TMPRSS2: A potential target ' 'for treatment of influenza virus and coronavirus infections. Biochimie. ' '2017;142:1–10. DOI: 10.1016/j.biochi.2017.07.016', 'DOI': '10.1016/j.biochi.2017.07.016'}, { 'key': 'ref30', 'doi-asserted-by': 'crossref', 'unstructured': 'Olaleye OA, Kaur M, Onyenaka CC. Ambroxol Hydrochloride Inhibits the ' 'Interaction between Severe Acute Respiratory Syndrome Coronavirus 2 ' 'Spike Protein’s Receptor Binding Domain and Recombinant Human ACE2. [Av. ' 'at: http://biorxiv.org/lookup/doi/10.1101/2020.09.13.295691]. 2020.', 'DOI': '10.1101/2020.09.13.295691'}, { 'key': 'ref31', 'doi-asserted-by': 'crossref', 'unstructured': 'Ansarin K, Tolouian R, Ardalan M, Taghizadieh A, Varshochi M, Teimouri S ' 'et al. Effect of bromhexine on clinical outcomes and mortality in ' 'COVID-19 patients: A randomized clinical trial. BioImpacts. ' '2020;10(4):209–15. DOI: 10.34172/bi.2020.27', 'DOI': '10.34172/bi.2020.27'}, { 'key': 'ref32', 'unstructured': 'Yavas G, Yavas C, Celik E, Sen E, Ata O, Afsar RE. The impact of ' 'spironolactone on the lung injury induced by concomitant trastuzumab and ' 'thoracic radiotherapy. International Journal of Radiation Research. ' '2019;17(1):87–95. [Av. at: http://ijrr.com/article1-2461-en.html]'}, { 'key': 'ref33', 'doi-asserted-by': 'crossref', 'unstructured': 'Chen D, Li X, Song Q, Hu C, Su F, Dai J et al. Assessment of Hypokalemia ' 'and Clinical Characteristics in Patients With Coronavirus Disease 2019 ' 'in Wenzhou, China. JAMA Network Open. 2020;3(6):e2011122. DOI: ' '10.1001/jamanetworkopen.2020.11122', 'DOI': '10.1001/jamanetworkopen.2020.11122'}, { 'key': 'ref34', 'doi-asserted-by': 'crossref', 'unstructured': 'Juurlink DN, Mamdani MM, Lee DS, Kopp A, Austin PC, Laupacis A et al. ' 'Rates of Hyperkalemia after Publication of the Randomized Aldactone ' 'Evaluation Study. New England Journal of Medicine. 2004;351(6):543–51. ' 'DOI: 10.1056/NEJMoa040135', 'DOI': '10.1056/NEJMoa040135'}, { 'key': 'ref35', 'unstructured': 'The Human Protein Atlas. Tissue expression of ADAM17. [Internet] ' 'Available at: ' 'https://www.proteinatlas.org/ENSG00000151694-ADAM17/tissue'}, { 'key': 'ref36', 'unstructured': 'Lin B, Ferguson C, White JT, Wang S, Vessella R, True LD et al. ' 'Prostate-localized and androgen-regulated expression of the ' 'membrane-bound serine protease TMPRSS2. Cancer Research. ' '1999;59(17):4180–4. PMID: 10485450'}, { 'key': 'ref37', 'doi-asserted-by': 'crossref', 'unstructured': 'Mikkonen L, Pihlajamaa P, Sahu B, Zhang F-P, Jänne OA. Androgen receptor ' 'and androgen-dependent gene expression in lung. Molecular and Cellular ' 'Endocrinology. 2010;317(1–2):14–24. DOI: 10.1016/j.mce.2009.12.022', 'DOI': '10.1016/j.mce.2009.12.022'}, { 'key': 'ref38', 'doi-asserted-by': 'crossref', 'unstructured': 'Montopoli M, Zumerle S, Vettor R, Rugge M, Zorzi M, Catapano V et al. ' 'Androgen-deprivation therapies for prostate cancer and risk of infection ' 'by SARS-CoV-2: a population-based study (N = 4532). Annals of Oncology. ' '2020;31(8):1040–5. DOI: 10.1016/j.annonc.2020.04.479', 'DOI': '10.1016/j.annonc.2020.04.479'}, { 'key': 'ref39', 'doi-asserted-by': 'crossref', 'unstructured': 'Loriaux DL. Spironolactone and Endocrine Dysfunction. Annals of Internal ' 'Medicine. 1976;85(5):630. DOI: 10.7326/0003-4819-85-5-630', 'DOI': '10.7326/0003-4819-85-5-630'}, { 'key': 'ref40', 'doi-asserted-by': 'crossref', 'unstructured': 'McMullen GR, Van Herle AJ. Hirsutism and the effectiveness of ' 'spironolactone in its management. Journal of Endocrinological ' 'Investigation. 1993;16(11):925–32. DOI: 10.1007/BF03348960', 'DOI': '10.1007/BF03348960'}, { 'key': 'ref41', 'doi-asserted-by': 'crossref', 'unstructured': 'Liaudet L, Szabo C. Blocking mineralocorticoid receptor with ' 'spironolactone may have a wide range of therapeutic actions in severe ' 'COVID-19 disease. Critical Care. 2020;24(1):318. DOI: ' '10.1186/s13054-020-03055-6', 'DOI': '10.1186/s13054-020-03055-6'}, { 'key': 'ref42', 'unstructured': 'Flávio C, Wambier C, Goren A. Spironolactone protection for SARSCoV-2: ' 'Targeting androgens and angiotensin converting enzyme 2 (ACE2). ' 'ResearchGate. 2020; [Av. at: ' 'https://www.researchgate.net/publication/341103985]'}], 'container-title': 'Kardiologiia', 'original-title': [], 'link': [ { 'URL': 'https://lib.ossn.ru/jour/article/viewFile/1440/861', 'content-type': 'application/pdf', 'content-version': 'vor', 'intended-application': 'text-mining'}], 'deposited': { 'date-parts': [[2021, 11, 11]], 'date-time': '2021-11-11T11:30:52Z', 'timestamp': 1636630252000}, 'score': 1, 'resource': {'primary': {'URL': 'https://lib.ossn.ru/jour/article/view/1440'}}, 'subtitle': [], 'short-title': [], 'issued': {'date-parts': [[2020, 12, 3]]}, 'references-count': 42, 'journal-issue': {'issue': '11', 'published-online': {'date-parts': [[2020, 12, 3]]}}, 'URL': 'http://dx.doi.org/10.18087/cardio.2020.11.n1440', 'relation': {}, 'ISSN': ['2412-5660', '0022-9040'], 'subject': ['Cardiology and Cardiovascular Medicine'], 'container-title-short': 'Kardiologiia', 'published': {'date-parts': [[2020, 12, 3]]}}