In-hospital mortality outcomes of favipiravir in patients with moderate to severe COVID-19 infection: An emulated target trial using real-world data from the largest field hospital in Thailand

DOI record: { "DOI": "10.1371/journal.pone.0324903", "ISSN": [ "1932-6203" ], "URL": "http://dx.doi.org/10.1371/journal.pone.0324903", "abstract": "<jats:sec id=\"sec001\">\n<jats:title>Background</jats:title>\n<jats:p>Favipiravir, an antiviral agent, has been widely used to treat COVID-19 due to its potential mechanism of action, despite limited evidence of its efficacy in moderate to severe cases.</jats:p>\n</jats:sec>\n<jats:sec id=\"sec002\">\n<jats:title>Aim</jats:title>\n<jats:p>This study aimed to evaluate the efficacy of favipiravir in improving in-hospital mortality outcomes among patients with moderate to severe COVID-19 through an emulation of a target trial.</jats:p>\n</jats:sec>\n<jats:sec id=\"sec003\">\n<jats:title>Methods</jats:title>\n<jats:p>We emulated a target trial using observational data from Bussarakham field hospital, Thailand between May 14 and September 20, 2021. Patients were categorized into three groups: those receiving favipiravir with dexamethasone (FPV with Dexa), favipiravir alone (FPV), and symptomatic treatment (ST). In-hospital mortality within 30 days was the primary outcome.</jats:p>\n</jats:sec>\n<jats:sec id=\"sec004\">\n<jats:title>Results</jats:title>\n<jats:p>From 18,184 patients admitted to the hospital, a total of 3,193 moderate to severe COVID-19 cases were included. Of these, 2,256 (70.65%) received FPV with Dexa, 828 (25.93%) received FPV, and 109 (3.41%) received ST. The restricted mean survival times were 29.68 days (95% CI: 29.52, 29.84) for FPV with Dexa, 29.46 days (95% CI: 29.22, 29.71) for FPV, and 28.14 days (95% CI: 26.51, 29.76) for ST. Only FPV showed marginally significant difference when compared to ST. However, there was a trend in prolonging survival time in FPV with Dexa group, and the results were more pronounced in severe and hypoxic patients. </jats:p>\n</jats:sec>\n<jats:sec id=\"sec005\">\n<jats:title>Conclusion</jats:title>\n<jats:p>Our emulated target trial suggests favipiravir, especially with dexamethasone, offers a modest survival benefit in moderate to severe COVID-19, particularly in hypoxic patients. It supports favipiravir as a practical antiviral in settings where other antivirals are not available. Further randomized controlled studies are needed to confirm its role, alongside standard corticosteroid therapy.</jats:p>\n</jats:sec>", "author": [ { "affiliation": [], "family": "Lumkul", "given": "Lalita", "sequence": "first" }, { "affiliation": [], "family": "Tanasombatkul", "given": "Krittai", "sequence": "additional" }, { "affiliation": [], "family": "Nitikaroon", "given": "Phongsak", "sequence": "additional" }, { "affiliation": [], "family": "Morasert", "given": "Thotsaporn", "sequence": "additional" }, { "ORCID": "https://orcid.org/0000-0002-8543-6254", "affiliation": [], "authenticated-orcid": true, "family": "Phinyo", "given": "Phichayut", "sequence": "additional" } ], "container-title": "PLOS One", "container-title-short": "PLoS One", "content-domain": { "crossmark-restriction": false, "domain": [ "www.plosone.org" ] }, "created": { "date-parts": [ [ 2025, 6, 4 ] ], "date-time": "2025-06-04T18:07:39Z", "timestamp": 1749060459000 }, "deposited": { "date-parts": [ [ 2025, 6, 4 ] ], "date-time": "2025-06-04T18:07:51Z", "timestamp": 1749060471000 }, "editor": [ { "affiliation": [], "family": "Bertagnin", "given": "Chiara", "sequence": "first" } ], "indexed": { "date-parts": [ [ 2025, 6, 5 ] ], "date-time": "2025-06-05T04:15:45Z", "timestamp": 1749096945611, "version": "3.41.0" }, "is-referenced-by-count": 0, "issue": "6", "issued": { "date-parts": [ [ 2025, 6, 4 ] ] }, "journal-issue": { "issue": "6", "published-online": { "date-parts": [ [ 2025, 6, 4 ] ] } }, "language": "en", "license": [ { "URL": "http://creativecommons.org/licenses/by/4.0/", "content-version": "vor", "delay-in-days": 0, "start": { "date-parts": [ [ 2025, 6, 4 ] ], "date-time": "2025-06-04T00:00:00Z", "timestamp": 1748995200000 } } ], "link": [ { "URL": "https://dx.plos.org/10.1371/journal.pone.0324903", "content-type": "unspecified", "content-version": "vor", "intended-application": "similarity-checking" } ], "member": "340", "original-title": [], "page": "e0324903", "prefix": "10.1371", "published": { "date-parts": [ [ 2025, 6, 4 ] ] }, "published-online": { "date-parts": [ [ 2025, 6, 4 ] ] }, "publisher": "Public Library of Science (PLoS)", "reference": [ { "DOI": "10.1016/j.ijsu.2020.02.034", "article-title": "World Health Organization declares global emergency: A review of the 2019 novel coronavirus (COVID-19)", "author": "C Sohrabi", "doi-asserted-by": "crossref", "first-page": "71", "journal-title": "Int J Surg", "key": "pone.0324903.ref001", "volume": "76", "year": "2020" }, { "key": "pone.0324903.ref002", "year": "2024" }, { "DOI": "10.1016/j.mjafi.2020.08.004", "article-title": "Favipiravir: A new and emerging antiviral option in COVID-19", "author": "U Agrawal", "doi-asserted-by": "crossref", "first-page": "370", "issue": "4", "journal-title": "Med J Armed Forces India", "key": "pone.0324903.ref003", "volume": "76", "year": "2020" }, { "author": "Department of Medical Services T", "key": "pone.0324903.ref004", "volume-title": "COVID-19 treatment guidelines", "year": "2020" }, { "article-title": "Assessment of outcomes following implementation of antiviral treatment guidelines for covid-19 during the first wave in thailand", "author": "N Sawanpanyalert", "first-page": "572", "issue": "4", "journal-title": "Southeast Asian J Trop Med Public Health", "key": "pone.0324903.ref005", "volume": "52", "year": "2021" }, { "DOI": "10.1016/j.pharmthera.2020.107512", "article-title": "Favipiravir, an anti-influenza drug against life-threatening RNA virus infections", "author": "K Shiraki", "doi-asserted-by": "crossref", "first-page": "107512", "journal-title": "Pharmacol Ther", "key": "pone.0324903.ref006", "volume": "209", "year": "2020" }, { "key": "pone.0324903.ref007", "unstructured": "Rattanachaikunsopon PPP. 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