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"abstract": "<jats:sec id=\"sec001\">\n<jats:title>Objective</jats:title>\n<jats:p>In this study, we evaluated the efficacy of hydroxychloroquine (HCQ) against coronavirus disease 2019 (COVID-19) via a randomized controlled trial (RCT) and a retrospective study.</jats:p>\n</jats:sec>\n<jats:sec id=\"sec002\">\n<jats:title>Methods</jats:title>\n<jats:p>Subjects admitted to 11 designated public hospitals in Taiwan between April 1 and May 31, 2020, with COVID-19 diagnosis confirmed by pharyngeal real-time RT-PCR for SARS-CoV-2, were randomized at a 2:1 ratio and stratified by mild or moderate illness. HCQ (400 mg twice for 1 d or HCQ 200 mg twice daily for 6 days) was administered. Both the study and control group received standard of care (SOC). Pharyngeal swabs and sputum were collected every other day. The proportion and time to negative viral PCR were assessed on day 14. In the retrospective study, medical records were reviewed for patients admitted before March 31, 2020.</jats:p>\n</jats:sec>\n<jats:sec id=\"sec003\">\n<jats:title>Results</jats:title>\n<jats:p>There were 33 and 37 cases in the RCT and retrospective study, respectively. In the RCT, the median times to negative rRT-PCR from randomization to hospital day 14 were 5 days (95% CI; 1, 9 days) and 10 days (95% CI; 2, 12 days) for the HCQ and SOC groups, respectively (<jats:italic>p</jats:italic> = 0.40). On day 14, 81.0% (17/21) and 75.0% (9/12) of the subjects in the HCQ and SOC groups, respectively, had undetected virus (<jats:italic>p</jats:italic> = 0.36). In the retrospective study, 12 (42.9%) in the HCQ group and 5 (55.6%) in the control group had negative rRT-PCR results on hospital day 14 (<jats:italic>p</jats:italic> = 0.70).</jats:p>\n</jats:sec>\n<jats:sec id=\"sec004\">\n<jats:title>Conclusions</jats:title>\n<jats:p>Neither study demonstrated that HCQ shortened viral shedding in mild to moderate COVID-19 subjects.</jats:p>\n</jats:sec>",
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"unstructured": "World Health Organization. Naming the coronavirus disease (COVID-19) and the viral that caused it [cited 2020 June 20]. Available from: https://www.who.int/emergencies/diseases/novel-coronavirus-2019/technical-guidance/naming-the-coronavirus-disease-(covid-2019)-and-the-virus-that-causes-it"
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"key": "pone.0242763.ref003",
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},
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"key": "pone.0242763.ref004",
"unstructured": "World Health Organization. Novel coronavirus situation report-151. Geneva, Switzerland [cited 2020 June 20]. Available from: https://www.who.int/docs/default-source/coronaviruse/situation-reports/20200619-covid-19-sitrep-151.pdf?sfvrsn=8b23b56e_2"
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"DOI": "10.1016/j.jfma.2020.02.007",
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"author": "SC Cheng",
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"journal-title": "J Formos Med Assoc",
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"year": "2020"
},
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"key": "pone.0242763.ref006",
"unstructured": "Taiwan Centers for Disease Control. CECC confirmed 1 more imported COVID-19 case; case returns to Taiwan from Bangladesh [cited 2020 June 20]. Accessed on: https://www.cdc.gov.tw/En/Bulletin/Detail/l7L0KFRR2KRBn1JygBFPUg?typeid=158"
},
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"DOI": "10.1056/NEJMoa2001191",
"article-title": "First case of 2019 novel coronavirus in the United States",
"author": "ML Holshue",
"doi-asserted-by": "crossref",
"first-page": "926",
"journal-title": "N Engl J Med",
"key": "pone.0242763.ref007",
"volume": "382",
"year": "2020"
},
{
"DOI": "10.1038/s41422-020-0282-0",
"article-title": "Remdesivir and chloroquine effectively inhibit the recently emerged novel coronavirus (2019-nCoV) in vitro",
"author": "M Wang",
"doi-asserted-by": "crossref",
"first-page": "269",
"journal-title": "Cell Res",
"key": "pone.0242763.ref008",
"volume": "30",
"year": "2020"
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"DOI": "10.1038/s41467-019-13940-6",
"article-title": "Comparative therapeutic efficacy of remdesivir and combination lopinavir, ritonavir, and interferon beta against MERS-CoV",
"author": "TP Sheahan",
"doi-asserted-by": "crossref",
"first-page": "222",
"journal-title": "Nat Commun",
"key": "pone.0242763.ref009",
"volume": "11",
"year": "2020"
},
{
"DOI": "10.2183/pjab.93.027",
"article-title": "Favipiravir (T-705), a broad spectrum inhibitor of viral RNA polymerase",
"author": "Y Furuta",
"doi-asserted-by": "crossref",
"first-page": "449",
"journal-title": "Proc Jpn Acad Ser B Phys Biol Sci",
"key": "pone.0242763.ref010",
"volume": "93",
"year": "2017"
},
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"article-title": "Lopinavir/ritonavir did not shorten the duration of SARS CoV-2 shedding in patients with mild pneumonia",
"author": "CY Cheng",
"first-page": "488",
"journal-title": "Taiwan. J Microbiol Infect Immunol. 2020",
"key": "pone.0242763.ref011",
"volume": "53"
},
{
"DOI": "10.1056/NEJMoa2001282",
"article-title": "A trial of lopinavir-ritonavir in adults hospitalized with severe COVID-19",
"author": "B Cao",
"doi-asserted-by": "crossref",
"first-page": "1787",
"journal-title": "New Engl J Med",
"key": "pone.0242763.ref012",
"volume": "382",
"year": "2020"
},
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"DOI": "10.1016/j.antiviral.2020.104787",
"article-title": "The FDA-approved drug ivermectin inhibits the replication of SARS-CoV-2 in vitro",
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"doi-asserted-by": "crossref",
"first-page": "104787",
"journal-title": "Antiviral Res",
"key": "pone.0242763.ref013",
"volume": "178",
"year": "2020"
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"DOI": "10.1016/j.cell.2020.04.004",
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"journal-title": "Cell",
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"volume": "181",
"year": "2020"
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"author": "P Gautret",
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"first-page": "105949",
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"volume": "20",
"year": "2020"
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"DOI": "10.1016/j.chom.2020.04.009",
"article-title": "Complex immune dysregulation in COVID-19 patients with severe respiratory failure",
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"key": "pone.0242763.ref016",
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"author": "S Rose-John",
"doi-asserted-by": "crossref",
"first-page": "1237",
"journal-title": "Int J Biol Sci",
"key": "pone.0242763.ref017",
"volume": "8",
"year": "2012"
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"DOI": "10.1016/S1473-3099(03)00806-5",
"article-title": "Effects of chloroquine on viral infections: an old drug against today’s diseases",
"author": "A Savarino",
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"first-page": "722",
"journal-title": "Lancet Infect Dis",
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"volume": "3",
"year": "2003"
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"article-title": "Chloroquine is a potent inhibitor of SARS coronavirus infection and spread",
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"first-page": "69",
"journal-title": "Virol J",
"key": "pone.0242763.ref019",
"volume": "2",
"year": "2005"
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"DOI": "10.1016/j.phrs.2020.104854",
"article-title": "Current targeted therapeutics against COVID-19: based on first-line experience in China",
"author": "Y Zhang",
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"first-page": "104854",
"journal-title": "Pharmacol Res",
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"volume": "157",
"year": "2020"
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"key": "pone.0242763.ref021",
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"author": "MR Mehra",
"journal-title": "N Engl J Med",
"key": "pone.0242763.ref022",
"year": "2020"
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"article-title": "Retraction—hydroxychloroquine or chloroquine with or without a macrolide for treatment of COVID-19: a multinational registry analysis",
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},
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"DOI": "10.5582/bst.2020.01047",
"article-title": "Breakthrough: chloroquine phosphate has shown apparent efficacy in treatment of COVID-19 associated pneumonia in clinical studies",
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"author": "J Geleris",
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"volume": "7",
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"author": "S Arshada",
"first-page": "396",
"journal-title": "J Infect Dis",
"key": "pone.0242763.ref030",
"volume": "97",
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"article-title": "A pilot study of hydroxychloroquine in treatment of patients with common coronavirus disease-19 (COVID-19)",
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"journal-title": "Zhejiang Da Xue Xue Bao Yi Xue Ban",
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"volume": "49",
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"article-title": "In vitro antiviral activity and projection of optimized dosing design of hydroxychloroquine for the treatment of severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)",
"author": "X Yao",
"first-page": "ciaa237",
"journal-title": "Clin Infect Dis",
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