{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,14]],"date-time":"2026-01-14T19:08:48Z","timestamp":1768417728872,"version":"3.49.0"},"reference-count":21,"publisher":"MDPI AG","issue":"16","license":[{"start":{"date-parts":[[2021,8,12]],"date-time":"2021-08-12T00:00:00Z","timestamp":1628726400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea","doi-asserted-by":"publisher","award":["2020M3A9I2081699"],"award-info":[{"award-number":["2020M3A9I2081699"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100016341","name":"Korea University Guro Hospital","doi-asserted-by":"publisher","award":["I2000171"],"award-info":[{"award-number":["I2000171"]}],"id":[{"id":"10.13039\/100016341","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCM"],"abstract":"<jats:p>Although some intravenous drugs have been used to treat coronavirus disease 2019 (COVID-19), no effective antiviral agents are currently available in the outpatient setting. We aimed to evaluate the efficacy and adverse events of 14-day ciclesonide treatment vs. standard care for patients with mild-to-moderate COVID-19. A randomized, open-label, multicenter clinical trial of ciclesonide inhalers was conducted in patients with mild-to-moderate COVID-19. Patients were enrolled within 3 days of diagnosis or within 7 days from symptom onset and randomly assigned to receive either ciclesonide (320 \u00b5g inhalation twice per day for 14 days) or standard care. The primary endpoint was the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) eradication rate on day 14 from study enrollment. Clinical status was assessed once daily, and serial nasopharyngeal viral load was evaluated by quantitative reverse transcription polymerase chain reaction. There were 35 and 26 patients in the ciclesonide and standard care groups, respectively. The SARS-CoV-2 eradication rate at day 14 was significantly higher in the ciclesonide group (p = 0.021). In multivariate analysis, SARS-CoV-2 negative conversion within 14 days was 12 times more likely in the ciclesonide group (95% confidence interval, 1.187\u2013125.240). Additionally, the clinical failure rate (high-flow nasal oxygen therapy or mechanical ventilation) was significantly lower in the ciclesonide group (p = 0.034). In conclusion, ciclesonide inhalation shortened SARS-CoV-2 viral shedding duration, and it may inhibit the progression to acute respiratory failure in patients with mild-to-moderate COVID-19. Clinical Trial Registration NCT04330586.<\/jats:p>","DOI":"10.3390\/jcm10163545","type":"journal-article","created":{"date-parts":[[2021,8,12]],"date-time":"2021-08-12T10:54:41Z","timestamp":1628765681000},"page":"3545","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":34,"title":["Ciclesonide Inhaler Treatment for Mild-to-Moderate COVID-19: A Randomized, Open-Label, Phase 2 Trial"],"prefix":"10.3390","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0148-7194","authenticated-orcid":false,"given":"Joon-Young","family":"Song","sequence":"first","affiliation":[{"name":"Division of Infectious Disease, Department of Internal Medicine, Korea University Guro Hospital, Korea University College of Medicine, Seoul 08308, Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jin-Gu","family":"Yoon","sequence":"additional","affiliation":[{"name":"Division of Infectious Disease, Department of Internal Medicine, Korea University Guro Hospital, Korea University College of Medicine, Seoul 08308, Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5183-1996","authenticated-orcid":false,"given":"Yu-Bin","family":"Seo","sequence":"additional","affiliation":[{"name":"Division of Infectious Diseases, Department of Internal Medicine, Hallym University College of Medicine, Chuncheon 24252, Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jacob","family":"Lee","sequence":"additional","affiliation":[{"name":"Division of Infectious Diseases, Department of Internal Medicine, Hallym University College of Medicine, Chuncheon 24252, Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Joong-Sik","family":"Eom","sequence":"additional","affiliation":[{"name":"Division of Infectious Diseases, Department of Internal Medicine, Gil Medical Center, Gachon University College of Medicine, Incheon 21565, Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jin-Soo","family":"Lee","sequence":"additional","affiliation":[{"name":"Division of Infectious Diseases, Department of Internal Medicine, Inha University College of Medicine, Incheon 22332, Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Won-Suk","family":"Choi","sequence":"additional","affiliation":[{"name":"Division of Infectious Diseases, Department of Internal Medicine, Korea University Ansan Hospital, Korea University College of Medicine, Ansan 15255, Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Eun-Young","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Seoul Metropolitan Government-Seoul National University Boramae Medical Center, Seoul 07061, Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2635-6315","authenticated-orcid":false,"given":"Young-Ah","family":"Choi","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Seoul Metropolitan Seobuk Hospital, Seoul 03433, Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hak-Jun","family":"Hyun","sequence":"additional","affiliation":[{"name":"Division of Infectious Disease, Department of Internal Medicine, Korea University Guro Hospital, Korea University College of Medicine, Seoul 08308, Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hye","family":"Seong","sequence":"additional","affiliation":[{"name":"Division of Infectious Disease, Department of Internal Medicine, Korea University Guro Hospital, Korea University College of Medicine, Seoul 08308, Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ji-Yun","family":"Noh","sequence":"additional","affiliation":[{"name":"Division of Infectious Disease, Department of Internal Medicine, Korea University Guro Hospital, Korea University College of Medicine, Seoul 08308, Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hee-Jin","family":"Cheong","sequence":"additional","affiliation":[{"name":"Division of Infectious Disease, Department of Internal Medicine, Korea University Guro Hospital, Korea University College of Medicine, Seoul 08308, Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4546-3880","authenticated-orcid":false,"given":"Woo-Joo","family":"Kim","sequence":"additional","affiliation":[{"name":"Division of Infectious Disease, Department of Internal Medicine, Korea University Guro Hospital, Korea University College of Medicine, Seoul 08308, Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2021,8,12]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1858","DOI":"10.1056\/NEJMc2001801","article-title":"Covid-19 in South Korea\u2014Challenges of subclinical manifestations","volume":"382","author":"Song","year":"2020","journal-title":"N. Engl. J. Med."},{"key":"ref_2","unstructured":"World Health Organization (2020, November 28). Coronavirus Disease 2019 (COVID-19): Situation Report. Available online: https:\/\/www.who.int\/emergencies\/diseases\/novel-coronavirus-2019\/situation-reports."},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Jeon, S., Ko, M., Lee, J., Choi, I., Byun, S.Y., Park, S., Shum, D., and Kim, S. (2020). Identification of antiviral drug candidates against SARS-CoV-2 from FDA-approved drugs. Antimicrob. Agents Chemother., 64.","DOI":"10.1128\/AAC.00819-20"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"114184","DOI":"10.1016\/j.bcp.2020.114184","article-title":"COVID-19: An overview of the current pharmacological interventions, vaccines, and clinical trials","volume":"180","author":"Chakraborty","year":"2020","journal-title":"Biochem. Pharmacol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"2041","DOI":"10.1056\/NEJMoa2019014","article-title":"Hydroxychloroquine with or without azithromycin in mild-to-moderate Covid-19","volume":"383","author":"Cavalcanti","year":"2020","journal-title":"N. Engl. J. Med."},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Recovery Collaborative Group, Horby, P., Mafham, M., Linsell, L., Bell, J.L., Staplin, N., Emberson, J.R., Wiselka, M., Ustianowski, A., and Elmahi, E. (2020). Effect of hydroxychloroquine in hospitalized patients with Covid-19. N. Engl. J. Med., 383, 2030\u20132040.","DOI":"10.1056\/NEJMoa2022926"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1787","DOI":"10.1056\/NEJMoa2001282","article-title":"A trial of lopinavir-ritonavir in adults hospitalized with severe Covid-19","volume":"382","author":"Cao","year":"2020","journal-title":"N. Engl. J. Med."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1813","DOI":"10.1056\/NEJMoa2007764","article-title":"Remdesivir for the treatment of Covid-19\u2014Final report","volume":"383","author":"Beigel","year":"2020","journal-title":"N. Engl. J. Med."},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Matsuyama, S., Kawase, M., Nao, N., Shirato, K., Ujike, M., Kamitani, W., Shimojima, M., and Fukushi, S. (2020). The inhaled steroid ciclesonide blocks SARS-CoV-2 RNA Replication by targeting the viral replication-transcription complex in cultured cells. J. Virol., 95.","DOI":"10.1128\/JVI.01648-20"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"625","DOI":"10.1016\/j.jiac.2020.04.007","article-title":"Therapeutic potential of ciclesonide inahalation for COVID-19 pneumonia: Report of three cases","volume":"26","author":"Iwabuchi","year":"2020","journal-title":"J. Infect. Chemother."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"109","DOI":"10.1016\/j.jmii.2020.09.003","article-title":"Triple therapy with hydroxychloroquine, azithromycin, and ciclesonide for COVID-19 pneumonia","volume":"54","author":"Mori","year":"2021","journal-title":"J. Microbiol. Immunol. Infect."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"79","DOI":"10.5603\/ARM.a2020.0173","article-title":"A review of ciclesonide in COVID-19. Still a long way to go","volume":"89","author":"Deokar","year":"2021","journal-title":"Adv. Respir. Med."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"e23830","DOI":"10.2196\/23830","article-title":"Efficacy and safety of inhaled ciclesonide in treating patients with asymptomatic or mild COVID-19 in the RACCO trial: Protocol for a multicenter, open-label, randomized controlled trial","volume":"9","author":"Suzuki","year":"2020","journal-title":"JMIR Res. Protoc."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"851","DOI":"10.1378\/chest.127.3.851","article-title":"Airway and systemic effects of hydrofluoroalkane formulations of high-dose ciclesonide and fluticasone in moderate persistent asthma","volume":"127","author":"Lee","year":"2005","journal-title":"Chest"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"330","DOI":"10.1016\/j.jaci.2020.05.029","article-title":"Molecular pharmacology of ciclesonide against SARS-CoV-2","volume":"146","author":"Kimura","year":"2020","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"120241","DOI":"10.1016\/j.ijpharm.2021.120241","article-title":"Visualizing the spatial localization of ciclesonide and its metabolites in rat lungs after inhalation of 1-\u00b5m aerosol of ciclesonide by desorption electrospray ionization-time of flight mass spectrometry imaging","volume":"595","author":"Yamamoto","year":"2021","journal-title":"Int. J. Pharm."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"38","DOI":"10.1186\/s13613-015-0081-9","article-title":"Extravascular lung water in critical care: Recent advances and clinical applications","volume":"5","author":"Jozwiak","year":"2015","journal-title":"Ann. Intensive Care"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"2451","DOI":"10.1056\/NEJMcp2009575","article-title":"Severe Covid-19","volume":"383","author":"Berlin","year":"2020","journal-title":"N. Engl. J. Med."},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Recovery Collaborative Group, Horby, P., Lim, W.S., Emberson, J.R., Mafham, M., Bell, J.L., Linsell, L., Staplin, N., Brightling, C., and Ustianowski, A. (2021). Dexamethasone in hospitalized patients with Covid-19. N. Engl. J. Med., 384, 693\u2013704.","DOI":"10.1056\/NEJMoa2021436"},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Ramakrishnan, S., Nicolau, D.V., Langford, B., Mahdi, M., Jeffers, H., Mwasuku, C., Krassowska, K., Fox, R., Binnian, I., and Glover, V. (2021). Inhaled budesonide in the treatment of early COVID-19 (STOIC): A phase 2, open-label, randomised controlled trial. Lancet Respir. Med.","DOI":"10.1101\/2021.02.04.21251134"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"e195","DOI":"10.3346\/jkms.2020.35.e195","article-title":"Clinical significance of a high SARS-CoV-2 viral load in the saliva","volume":"35","author":"Yoon","year":"2020","journal-title":"J. Korean Med. Sci."}],"container-title":["Journal of Clinical Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2077-0383\/10\/16\/3545\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T06:44:51Z","timestamp":1760165091000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2077-0383\/10\/16\/3545"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,8,12]]},"references-count":21,"journal-issue":{"issue":"16","published-online":{"date-parts":[[2021,8]]}},"alternative-id":["jcm10163545"],"URL":"https:\/\/doi.org\/10.3390\/jcm10163545","relation":{},"ISSN":["2077-0383"],"issn-type":[{"value":"2077-0383","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,8,12]]}}}