Clinical antiviral efficacy of favipiravir in early COVID-19 (PLATCOV): an open-label, randomised, controlled, adaptive platform trial
Viravarn Luvira, William H K Schilling, Podjanee Jittamala, James A Watson, Simon Boyd, Tanaya Siripoon, Thundon Ngamprasertchai, Pedro J Almeida, Maneerat Ekkapongpisit, Cintia Cruz, James J Callery, Shivani Singh, Runch Tuntipaiboontana, Varaporn Kruabkontho, Thatsanun Ngernseng, Jaruwan Tubprasert, Mohammad Yazid Abdad, Srisuda Keayarsa, Wanassanan Madmanee, Renato S Aguiar, Franciele M Santos, Pongtorn Hanboonkunupakarn, Borimas Hanboonkunupakarn, Kittiyod Poovorawan, Mallika Imwong, Walter R J Taylor, Vasin Chotivanich, Kesinee Chotivanich, Sasithon Pukrittayakamee, Arjen M Dondorp, Nicholas P J Day, Mauro M Teixeira, Watcharapong Piyaphanee, Weerapong Phumratanaprapin, Nicholas J White
BMC Infectious Diseases, doi:10.1186/s12879-023-08835-3
Brief summary In early symptomatic COVID-19 treatment, high dose oral favipiravir did not accelerate viral clearance. Background Favipiravir, an anti-influenza drug, has in vitro antiviral activity against SARS-CoV-2. Clinical trial evidence to date is inconclusive. Favipiravir has been recommended for the treatment of COVID-19 in some countries.
Methods In a multicentre open-label, randomised, controlled, adaptive platform trial, low-risk adult patients with early symptomatic COVID-19 were randomised to one of ten treatment arms including high dose oral favipiravir (3.6g on day 0 followed by 1.6g daily to complete 7 days treatment) or no study drug. The primary outcome was the rate of viral clearance (derived under a linear mixed-effects model from the daily log 10 viral densities in standardised duplicate oropharyngeal swab eluates taken daily over 8 days [18 swabs per patient]), assessed in a modified intention-to-treat population (mITT). The safety population included all patients who received at least one dose of the allocated intervention. This ongoing adaptive platform trial was registered at ClinicalTrials.gov (NCT05041907) on 13/09/2021. Results In the final analysis, the mITT population contained data from 114 patients randomised to favipiravir and 126 patients randomised concurrently to no study drug. Under the linear mixed-effects model fitted to all oropharyngeal viral density estimates in the first 8 days from randomisation (4,318 swabs), there was no difference in the rate of viral †
Supplementary Information The online version contains supplementary material available at https:// doi. org/ 10. 1186/ s12879-023-08835-3. Authors' contributions V.L., J.A.W., S.B., W.H.K.S., and N.J.W wrote the first draft of the manuscript. P.J., V.L., T.S., T.N., B.H., S.S., K.P., P.B., V.C., P.J.A., M.M., S.P., W.P., W.P. were responsible for collection of clinical data. T.N. was responsible for data curation. J.A.W. was responsible for statistical analysis and the figures. S.K., W.M., M.Y.A., R.A.S., F.M.S., R.T., M.I., K.C. were responsible for laboratory testing and analysis. V.K., J.T., were responsible for trial set-up and monitoring. C.C. was responsible for coordination of the study in Brazil and J.J.C. and S.B. for safety monitoring and document preparation. W.R.J.T., A.M.D, N.P.J.D, N.J.W supervised the study and gave scientific input. All authors reviewed the manuscript.
Additional file 1: Supplementary
Availability of data and materials All code and data are openly accessible via GitHub: https:// github. com/ jwato watson/ PLATC OV-Favip iravir. The final datasets will be stored locally and securely at the Mahidol Oxford Research Unit for long-term storage and access. Additional anonymised participant data can be made available by request on a case-by-case basis from the MORU Data Access Committee at datasharing@tropmedres.ac and can be made available by request to the corresponding author.
Declarations Ethics approval and consent to participate
..
References
Abdulrahman, Odat, Tayar, Rana, Alharthy, Favipiravir efficacy and safety for the treatment of severe coronavirus disease 2019: a retrospective study, J Ayub Med Coll Abbottabad
Bernal, Da Silva, Musungaie, Kovalchuk, Gonzalez et al., Molnupiravir for Oral Treatment of Covid-19 in Nonhospitalized Patients, N Engl J Med
Bosaeed, Alharbi, Alrehily, Bahlaq, Gaifer, Efficacy of favipiravir in adults with mild COVID-19: a randomized, double-blind, multicentre, placebo-controlled clinical trial, Clin Microbiol Infect
Butler, Hobbs, Gbinigie, Rahman, Hayward et al., Molnupiravir plus usual care versus usual care alone as early treatment for adults with COVID-19 at increased risk of adverse outcomes (PANORAMIC): an open-label, platform-adaptive randomised controlled trial, Lancet
Cai, Yang, Liu, Chen, Shu et al., Experimental treatment with favipiravir for COVID-19: an open-label control study, Engineering
Chuah, Chow, Hor, Cheng, Ker et al., Efficacy of early treatment with favipiravir on disease progression among high-risk patients with coronavirus disease 2019 (COVID-19): a randomized openlabel clinical trial, Clin Infect Dis
Coomes, Haghbayan, Favipiravir, an antiviral for COVID-19?, J Antimicrob Chemother
Doi, Hibino, Hase, Yamamoto, Kasamatsu et al., Prospective, randomized, open-label trial of early versus late favipiravir therapy in hospitalized patients with COVID-19, Antimicrob Agents Chemother
Doi, Ishihara, Banno, Ando, Kondo, Favipiravir Observational Study. Favipiravir for symptomatic COVID-19: a nationwide observational cohort study, J Infect Chemother
Driouich, Cochin, Lingas, Moureau, Touret et al., Favipiravir antiviral efficacy against SARS-CoV-2 in a hamster model, Nat Commun
Du, Chen, Favipiravir: pharmacokinetics and concerns about clinical trials for 2019-nCoV infection, Clin Pharmacol Ther
Fischer Wa 2nd, Eron, Jr, Holman, Cohen et al., A phase 2a clinical trial of molnupiravir in patients with COVID-19 shows accelerated SARS-CoV-2 RNA clearance and elimination of infectious virus, Sci Transl Med
Furuta, Gowen, Takahashi, Shiraki, Smee et al., Favipiravir (T-705), a novel viral RNA polymerase inhibitor, Antiviral Res
Furuta, Takahashi, Fukuda, Kuno, Kamiyama et al., In vitro and in vivo activities of anti-influenza virus compound T-705, Antimicrob Agents Chemother
Golan, Campos, Woolson, Cilla, Hanabergh et al., Favipiravir in patients with early mild-to-moderate COVID-19: a randomized controlled trial, Clin Infect Dis
Gottlieb, Vaca, Paredes, Mera, Webb et al., Early remdesivir to prevent progression to severe Covid-19 in outpatients, N Engl J Med
Hammond, Leister-Tebbe, Gardner, Abreu, Wisemandle, Oral nirmatrelvir for high-risk, nonhospitalized adults with Covid-19, N Engl J Med
Hassaniazad, Farshidi, Gharibzadeh, Bazram, Khalili et al., Efficacy and safety of favipiravir plus interferon-beta versus lopinavir/ritonavir plus interferon-beta in moderately ill patients with COVID-19: a randomized clinical trial, J Med Virol
Holubar, Subramanian, Purington, Hedlin, Bunning et al., Favipiravir for treatment of outpatients with asymptomatic or uncomplicated coronavirus disease 2019: a double-blind, randomized, placebo-controlled, phase 2 trial, Clin Infect Dis
Ivashchenko, Dmitriev, Vostokova, Azarova, Blinow et al., AVIFAVIR for treatment of patients with moderate coronavirus disease 2019 (COVID-19): interim results of a phase ii/iii multicenter randomized clinical trial, Clin Infect Dis
Jittamala, Schilling, Watson, Luvira, Siripoon et al., Clinical antiviral efficacy of remdesivir in COVID-19: an open label, randomized, controlled adaptive platform trial (PLATCOV), J Infect Dis,
doi:10.1093/infdis/jiad275Kaptein, Jacobs, Langendries, Seldeslachts, Horst et al., Favipiravir at high doses has potent antiviral activity in SARS-CoV-2-infected hamsters, whereas hydroxychloroquine lacks activity, Proc Natl Acad Sci
Khamis, Naabi, Lawati, Ambusaidi, Sharji et al., Randomized controlled open label trial on the use of favipiravir combined with inhaled interferon beta-1b in hospitalized patients with moderate to severe COVID-19 pneumonia, Int J Infect Dis
Lowe, Brown, Chowdhury, Davey, Yee et al., Favipiravir, lopinavir-ritonavir, or combination therapy (FLARE): a randomised, double-blind, 2 × 2 factorial placebo-controlled trial of early antiviral therapy in COVID-19, PLoS Med
Mcmahon, Lau, Coldham, Roney, Hagenauer et al., Favipiravir in early symptomatic COVID-19, a randomised placebo-controlled trial, EClinicalMedicine
Nguyen, Guedj, Anglaret, Laouénan, Madelain et al., Favipiravir pharmacokinetics in Ebola-Infected patients of the JIKI trial reveals concentrations lower than targeted, PLoS Negl Trop Dis
O'brien, Forleo-Neto, Musser, Chan, Sarkar, Covid-19 phase 3 prevention trial team. Subcutaneous REGEN-COV antibody combination to prevent Covid-19, N Engl J Med
Qahtani, Kumar, Aljawder, Abdulrahman, Mohamed et al., Randomized controlled trial of favipiravir, hydroxychloroquine, and standard care in patients with mild/moderate COVID-19 disease, Sci Rep
Reddy, Patil, Khobragade, Balki, Raj et al., Evaluation of the safety and efficacy of favipiravir in adult Indian patients with mild-to-moderate COVID-19 in a real-world setting, Int J Gen Med
Reis, Silva, Silva, Thabane, Milagres et al., Effect of early treatment with ivermectin among patients with Covid-19, N Engl J Med
Schilling, Jittamala, Watson, Boyd, Luvira et al., Antiviral efficacy of molnupiravir versus ritonavir-boosted nirmatrelvir in patients with early symptomatic COVID-19 (PLATCOV): an openlabel, phase 2, randomised, controlled, adaptive trial, Lancet Infect Dis,
doi:10.1016/S1473-3099(23)00493-0Schilling, Jittamala, Watson, Ekkapongpisit, Siripoon et al., Pharmacometrics of high-dose ivermectin in early COVID-19 from an open label, randomized, controlled adaptive platform trial (PLATCOV), Elife,
doi:10.7554/eLife.83201Sirijatuphat, Manosuthi, Niyomnaitham, Owen, Copeland et al., Early treatment of Favipiravir in COVID-19 patients without pneumonia: a multicentre, open-labelled, randomized control study, Emerg Microbes Infect
Sissoko, Laouenan, Folkesson, Lebing, Beavogui et al., Experimental treatment with favipiravir for ebola virus disease (the JIKI Trial): a historically controlled, single-arm proof-of-concept trial in Guinea, PLoS Med
Sitasuwan, Phisalprapa, Srivanichakorn, Washirasaksiri, Auesomwang et al., Early antiviral and supervisory dexamethasone treatment improve clinical outcomes of nonsevere COVID-19 patients, Medicine
Sleeman, Mishin, Deyde, Furuta, Klimov et al., In vitro antiviral activity of favipiravir (T-705) against drug-resistant influenza and 2009 A(H1N1) viruses, Antimicrob Agents Chemother
Solaymani-Dodaran, Ghanei, Bagheri, Qazvini, Vahedi et al., Safety and efficacy of Favipiravir in moderate to severe SARS-CoV-2 pneumonia, Int Immunopharmacol
Udwadia, Singh, Barkate, Patil, Rangwala et al., Efficacy and safety of favipiravir, an oral RNA-dependent RNA polymerase inhibitor, in mild-to-moderate COVID-19: a randomized, comparative, open-label, multicenter, phase 3 clinical trial, Int J Infect Dis
Wang, Cao, Zhang, Yang, Liu et al., Remdesivir and chloroquine effectively inhibit the recently emerged novel coronavirus (2019-nCoV) in vitro, Cell Res
Wang, Wu, Wang, Gao, Liu et al., Structural basis for RNA replication by the SARS-CoV-2 polymerase, Cell
Waters, Warren, Hughes, Lewis, Zhang, Human genetic risk of treatment with antiviral nucleoside analog drugs that induce lethal mutagenesis: the special case of molnupiravir, Environ Mol Mutagen
Watson, Kissler, Day, Grad, White, Characterizing SARS-CoV-2 viral clearance kinetics to improve the design of antiviral pharmacometric studies, Antimicrob Agents Chemother
Weinreich, Sivapalasingam, Norton, Ali, Gao et al., REGN-COV2, a neutralizing antibody cocktail, in outpatients with COVID-19, N Engl J Med
Zhao, Zhang, Zhu, Chen, Chen et al., Favipiravir in the treatment of patients with SARS-CoV-2 RNA recurrent positive after discharge: a multicenter, open-label, randomized trial, Int Immunopharmacol
{ 'indexed': {'date-parts': [[2024, 1, 16]], 'date-time': '2024-01-16T00:15:34Z', 'timestamp': 1705364134427},
'reference-count': 44,
'publisher': 'Springer Science and Business Media LLC',
'issue': '1',
'license': [ { 'start': { 'date-parts': [[2024, 1, 15]],
'date-time': '2024-01-15T00:00:00Z',
'timestamp': 1705276800000},
'content-version': 'tdm',
'delay-in-days': 0,
'URL': 'https://creativecommons.org/licenses/by/4.0'},
{ 'start': { 'date-parts': [[2024, 1, 15]],
'date-time': '2024-01-15T00:00:00Z',
'timestamp': 1705276800000},
'content-version': 'vor',
'delay-in-days': 0,
'URL': 'https://creativecommons.org/licenses/by/4.0'}],
'funder': [ { 'DOI': '10.13039/100010269',
'name': 'Wellcome Trust',
'doi-asserted-by': 'publisher',
'award': [ 'Other', 'Other', 'Other', '223195/Z/21/Z', 'Other', 'Other', 'Other',
'223195/Z/21/Z', 'Other', 'Other', 'Other', 'Other', 'Other', 'Other', 'Other',
'Other', 'Other', 'Other', 'Other', 'Other', 'Other', 'Other', 'Other']}],
'content-domain': {'domain': ['link.springer.com'], 'crossmark-restriction': False},
'abstract': '<jats:title>Abstract</jats:title><jats:sec>\n'
' <jats:title>Brief summary</jats:title>\n'
' <jats:p>In early symptomatic COVID-19 treatment, high dose oral favipiravir '
'did not accelerate viral clearance.</jats:p>\n'
' </jats:sec><jats:sec>\n'
' <jats:title>Background</jats:title>\n'
' <jats:p>Favipiravir, an anti-influenza drug, has in vitro antiviral activity '
'against SARS-CoV-2. Clinical trial evidence to date is inconclusive. Favipiravir has been '
'recommended for the treatment of COVID-19 in some countries.</jats:p>\n'
' </jats:sec><jats:sec>\n'
' <jats:title>Methods</jats:title>\n'
' <jats:p>In a multicentre open-label, randomised, controlled, adaptive '
'platform trial, low-risk adult patients with early symptomatic COVID-19 were randomised to '
'one of ten treatment arms including high dose oral favipiravir (3.6g on day 0 followed by '
'1.6g daily to complete 7 days treatment) or no study drug. The primary outcome was the rate '
'of viral clearance (derived under a linear mixed-effects model from the daily '
'log<jats:sub>10</jats:sub> viral densities in standardised duplicate oropharyngeal swab '
'eluates taken daily over 8 days [18 swabs per patient]), assessed in a modified '
'intention-to-treat population (mITT). The safety population included all patients who '
'received at least one dose of the allocated intervention. This ongoing adaptive platform '
'trial was registered at ClinicalTrials.gov (NCT05041907) on 13/09/2021.</jats:p>\n'
' </jats:sec><jats:sec>\n'
' <jats:title>Results</jats:title>\n'
' <jats:p>In the final analysis, the mITT population contained data from 114 '
'patients randomised to favipiravir and 126 patients randomised concurrently to no study drug. '
'Under the linear mixed-effects model fitted to all oropharyngeal viral density estimates in '
'the first 8 days from randomisation (4,318 swabs), there was no difference in the rate of '
'viral clearance between patients given favipiravir and patients receiving no study drug; a '
'-1% (95% credible interval: -14 to 14%) difference. High dose favipiravir was '
'well-tolerated.</jats:p>\n'
' </jats:sec><jats:sec>\n'
' <jats:title>Interpretation</jats:title>\n'
' <jats:p>Favipiravir does not accelerate viral clearance in early symptomatic '
'COVID-19. The viral clearance rate estimated\xa0from quantitative measurements of '
'oropharyngeal eluate viral densities assesses the antiviral efficacy of drugs in vivo with '
'comparatively few studied\xa0patients.</jats:p>\n'
' </jats:sec>',
'DOI': '10.1186/s12879-023-08835-3',
'type': 'journal-article',
'created': {'date-parts': [[2024, 1, 15]], 'date-time': '2024-01-15T11:02:18Z', 'timestamp': 1705316538000},
'update-policy': 'http://dx.doi.org/10.1007/springer_crossmark_policy',
'source': 'Crossref',
'is-referenced-by-count': 0,
'title': 'Clinical antiviral efficacy of favipiravir in early COVID-19 (PLATCOV): an open-label, '
'randomised, controlled, adaptive platform trial',
'prefix': '10.1186',
'volume': '24',
'author': [ {'given': 'Viravarn', 'family': 'Luvira', 'sequence': 'first', 'affiliation': []},
{'given': 'William H. K.', 'family': 'Schilling', 'sequence': 'additional', 'affiliation': []},
{'given': 'Podjanee', 'family': 'Jittamala', 'sequence': 'additional', 'affiliation': []},
{'given': 'James A.', 'family': 'Watson', 'sequence': 'additional', 'affiliation': []},
{'given': 'Simon', 'family': 'Boyd', 'sequence': 'additional', 'affiliation': []},
{'given': 'Tanaya', 'family': 'Siripoon', 'sequence': 'additional', 'affiliation': []},
{'given': 'Thundon', 'family': 'Ngamprasertchai', 'sequence': 'additional', 'affiliation': []},
{'given': 'Pedro J.', 'family': 'Almeida', 'sequence': 'additional', 'affiliation': []},
{'given': 'Maneerat', 'family': 'Ekkapongpisit', 'sequence': 'additional', 'affiliation': []},
{'given': 'Cintia', 'family': 'Cruz', 'sequence': 'additional', 'affiliation': []},
{'given': 'James J.', 'family': 'Callery', 'sequence': 'additional', 'affiliation': []},
{'given': 'Shivani', 'family': 'Singh', 'sequence': 'additional', 'affiliation': []},
{'given': 'Runch', 'family': 'Tuntipaiboontana', 'sequence': 'additional', 'affiliation': []},
{'given': 'Varaporn', 'family': 'Kruabkontho', 'sequence': 'additional', 'affiliation': []},
{'given': 'Thatsanun', 'family': 'Ngernseng', 'sequence': 'additional', 'affiliation': []},
{'given': 'Jaruwan', 'family': 'Tubprasert', 'sequence': 'additional', 'affiliation': []},
{'given': 'Mohammad Yazid', 'family': 'Abdad', 'sequence': 'additional', 'affiliation': []},
{'given': 'Srisuda', 'family': 'Keayarsa', 'sequence': 'additional', 'affiliation': []},
{'given': 'Wanassanan', 'family': 'Madmanee', 'sequence': 'additional', 'affiliation': []},
{'given': 'Renato S.', 'family': 'Aguiar', 'sequence': 'additional', 'affiliation': []},
{'given': 'Franciele M.', 'family': 'Santos', 'sequence': 'additional', 'affiliation': []},
{ 'given': 'Pongtorn',
'family': 'Hanboonkunupakarn',
'sequence': 'additional',
'affiliation': []},
{ 'given': 'Borimas',
'family': 'Hanboonkunupakarn',
'sequence': 'additional',
'affiliation': []},
{'given': 'Kittiyod', 'family': 'Poovorawan', 'sequence': 'additional', 'affiliation': []},
{'given': 'Mallika', 'family': 'Imwong', 'sequence': 'additional', 'affiliation': []},
{'given': 'Walter R. J.', 'family': 'Taylor', 'sequence': 'additional', 'affiliation': []},
{'given': 'Vasin', 'family': 'Chotivanich', 'sequence': 'additional', 'affiliation': []},
{'given': 'Kesinee', 'family': 'Chotivanich', 'sequence': 'additional', 'affiliation': []},
{'given': 'Sasithon', 'family': 'Pukrittayakamee', 'sequence': 'additional', 'affiliation': []},
{'given': 'Arjen M.', 'family': 'Dondorp', 'sequence': 'additional', 'affiliation': []},
{'given': 'Nicholas P. J.', 'family': 'Day', 'sequence': 'additional', 'affiliation': []},
{'given': 'Mauro M.', 'family': 'Teixeira', 'sequence': 'additional', 'affiliation': []},
{'given': 'Watcharapong', 'family': 'Piyaphanee', 'sequence': 'additional', 'affiliation': []},
{ 'given': 'Weerapong',
'family': 'Phumratanaprapin',
'sequence': 'additional',
'affiliation': []},
{'given': 'Nicholas J.', 'family': 'White', 'sequence': 'additional', 'affiliation': []},
{'name': 'the PLATCOV Collaborative Group', 'sequence': 'additional', 'affiliation': []}],
'member': '297',
'published-online': {'date-parts': [[2024, 1, 15]]},
'reference': [ { 'key': '8835_CR1',
'doi-asserted-by': 'publisher',
'first-page': '977',
'DOI': '10.1128/AAC.46.4.977-981.2002',
'volume': '46',
'author': 'Y Furuta',
'year': '2002',
'unstructured': 'Furuta Y, Takahashi K, Fukuda Y, Kuno M, Kamiyama T, Kozaki K, et al. In '
'vitro and in vivo activities of anti-influenza virus compound T-705. '
'Antimicrob Agents Chemother. 2002;46:977–81.',
'journal-title': 'Antimicrob Agents Chemother'},
{ 'key': '8835_CR2',
'doi-asserted-by': 'publisher',
'first-page': '446',
'DOI': '10.1016/j.antiviral.2013.09.015',
'volume': '100',
'author': 'Y Furuta',
'year': '2013',
'unstructured': 'Furuta Y, Gowen BB, Takahashi K, Shiraki K, Smee DF, Barnard DL. '
'Favipiravir (T-705), a novel viral RNA polymerase inhibitor. Antiviral '
'Res. 2013;100:446–54.',
'journal-title': 'Antiviral Res'},
{ 'key': '8835_CR3',
'doi-asserted-by': 'publisher',
'first-page': 'e1001967',
'DOI': '10.1371/journal.pmed.1001967',
'volume': '13',
'author': 'D Sissoko',
'year': '2016',
'unstructured': 'Sissoko D, Laouenan C, Folkesson E, M’Lebing AB, Beavogui AH, Baize S, '
'et al. Experimental treatment with favipiravir for ebola virus disease '
'(the JIKI Trial): a historically controlled, single-arm proof-of-concept '
'trial in Guinea. PLoS Med. 2016;13:e1001967.',
'journal-title': 'PLoS Med'},
{ 'key': '8835_CR4',
'doi-asserted-by': 'publisher',
'first-page': '269',
'DOI': '10.1038/s41422-020-0282-0',
'volume': '30',
'author': 'M Wang',
'year': '2020',
'unstructured': 'Wang M, Cao R, Zhang L, Yang X, Liu J, Xu M, et al. Remdesivir and '
'chloroquine effectively inhibit the recently emerged novel coronavirus '
'(2019-nCoV) in vitro. Cell Res. 2020;30:269–71.',
'journal-title': 'Cell Res'},
{ 'key': '8835_CR5',
'doi-asserted-by': 'publisher',
'first-page': '417',
'DOI': '10.1016/j.cell.2020.05.034',
'volume': '182',
'author': 'Q Wang',
'year': '2020',
'unstructured': 'Wang Q, Wu J, Wang H, Gao Y, Liu Q, Mu A, et al. Structural basis for '
'RNA replication by the SARS-CoV-2 polymerase. Cell. 2020;182:417–28.',
'journal-title': 'Cell'},
{ 'key': '8835_CR6',
'doi-asserted-by': 'publisher',
'first-page': '2013',
'DOI': '10.1093/jac/dkaa171',
'volume': '75',
'author': 'EA Coomes',
'year': '2020',
'unstructured': 'Coomes EA, Haghbayan H. Favipiravir, an antiviral for COVID-19? J '
'Antimicrob Chemother. 2020;75:2013–4.',
'journal-title': 'J Antimicrob Chemother'},
{ 'key': '8835_CR7',
'doi-asserted-by': 'publisher',
'first-page': '2517',
'DOI': '10.1128/AAC.01739-09',
'volume': '54',
'author': 'K Sleeman',
'year': '2010',
'unstructured': 'Sleeman K, Mishin VP, Deyde VM, Furuta Y, Klimov AI, Gubareva LV. In '
'vitro antiviral activity of favipiravir (T-705) against drug-resistant '
'influenza and 2009 A(H1N1) viruses. Antimicrob Agents Chemother. '
'2010;54:2517–24.',
'journal-title': 'Antimicrob Agents Chemother'},
{ 'key': '8835_CR8',
'doi-asserted-by': 'publisher',
'first-page': '26955',
'DOI': '10.1073/pnas.2014441117',
'volume': '117',
'author': 'SJF Kaptein',
'year': '2020',
'unstructured': 'Kaptein SJF, Jacobs S, Langendries L, Seldeslachts L, Ter Horst S, '
'Liesenborghs L, et al. Favipiravir at high doses has potent antiviral '
'activity in SARS-CoV-2-infected hamsters, whereas hydroxychloroquine '
'lacks activity. Proc Natl Acad Sci USA. 2020;117:26955–65.',
'journal-title': 'Proc Natl Acad Sci USA'},
{ 'key': '8835_CR9',
'doi-asserted-by': 'publisher',
'first-page': '1735',
'DOI': '10.1038/s41467-021-21992-w',
'volume': '12',
'author': 'JS Driouich',
'year': '2021',
'unstructured': 'Driouich JS, Cochin M, Lingas G, Moureau G, Touret F, Petit PR, et al. '
'Favipiravir antiviral efficacy against SARS-CoV-2 in a hamster model. '
'Nat Commun. 2021;12:1735.',
'journal-title': 'Nat Commun'},
{ 'key': '8835_CR10',
'doi-asserted-by': 'publisher',
'first-page': '4551',
'DOI': '10.2147/IJGM.S349241',
'volume': '15',
'author': 'PK Reddy',
'year': '2022',
'unstructured': 'Reddy PK, Patil S, Khobragade A, Balki A, Raj A, Kalikar M, et al. '
'Evaluation of the safety and efficacy of favipiravir in adult Indian '
'patients with mild-to-moderate COVID-19 in a real-world setting. Int J '
'Gen Med. 2022;15:4551–63.',
'journal-title': 'Int J Gen Med'},
{ 'key': '8835_CR11',
'doi-asserted-by': 'publisher',
'first-page': 'e31681',
'DOI': '10.1097/MD.0000000000031681',
'volume': '101',
'author': 'T Sitasuwan',
'year': '2022',
'unstructured': 'Sitasuwan T, Phisalprapa P, Srivanichakorn W, Washirasaksiri C, '
'Auesomwang C, Tinmanee R, et al. Early antiviral and supervisory '
'dexamethasone treatment improve clinical outcomes of nonsevere COVID-19 '
'patients. Medicine (Baltimore). 2022;101:e31681.',
'journal-title': 'Medicine (Baltimore)'},
{ 'issue': '10',
'key': '8835_CR12',
'doi-asserted-by': 'publisher',
'first-page': '1192',
'DOI': '10.1016/j.eng.2020.03.007',
'volume': '6',
'author': 'Q Cai',
'year': '2020',
'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;6(10):1192–8.',
'journal-title': 'Engineering'},
{ 'key': '8835_CR13',
'unstructured': 'Doi Y, Ishihara T, Banno S, Ando M, Kondo M. Favipiravir Observational '
'Study. Favipiravir for symptomatic COVID-19: a nationwide observational '
'cohort study. J Infect Chemother. 2022:S1341–321X(22)00291–4.'},
{ 'issue': '3',
'key': '8835_CR14',
'doi-asserted-by': 'publisher',
'first-page': '397',
'DOI': '10.55519/JAMC-03-10305',
'volume': '34',
'author': 'B Abdulrahman',
'year': '2022',
'unstructured': 'Abdulrahman B, Mady A, Odat MA, Tayar AA, Rana MA, Alharthy A, et al. '
'Favipiravir efficacy and safety for the treatment of severe coronavirus '
'disease 2019: a retrospective study. J Ayub Med Coll Abbottabad. '
'2022;34(3):397–402.',
'journal-title': 'J Ayub Med Coll Abbottabad'},
{ 'key': '8835_CR15',
'doi-asserted-by': 'publisher',
'first-page': '2197',
'DOI': '10.1080/22221751.2022.2117092',
'volume': '11',
'author': 'R Sirijatuphat',
'year': '2022',
'unstructured': 'Sirijatuphat R, Manosuthi W, Niyomnaitham S, Owen A, Copeland KK, '
'Charoenpong L, et al. Early treatment of Favipiravir in COVID-19 '
'patients without pneumonia: a multicentre, open-labelled, randomized '
'control study. Emerg Microbes Infect. 2022;11:2197–206.',
'journal-title': 'Emerg Microbes Infect'},
{ 'key': '8835_CR16',
'doi-asserted-by': 'publisher',
'first-page': 'e01897',
'DOI': '10.1128/AAC.01897-20',
'volume': '64',
'author': 'Y Doi',
'year': '2020',
'unstructured': 'Doi Y, Hibino M, Hase R, Yamamoto M, Kasamatsu Y, Hirose M, et al. '
'Prospective, randomized, open-label trial of early versus late '
'favipiravir therapy in hospitalized patients with COVID-19. Antimicrob '
'Agents Chemother. 2020;64:e01897–20.',
'journal-title': 'Antimicrob Agents Chemother.'},
{ 'key': '8835_CR17',
'doi-asserted-by': 'publisher',
'first-page': '538',
'DOI': '10.1016/j.ijid.2020.11.008',
'volume': '102',
'author': 'F Khamis',
'year': '2021',
'unstructured': 'Khamis F, Al Naabi H, Al Lawati A, Ambusaidi Z, Al Sharji M, Al Barwani '
'U, et al. Randomized controlled open label trial on the use of '
'favipiravir combined with inhaled interferon beta-1b in hospitalized '
'patients with moderate to severe COVID-19 pneumonia. Int J Infect Dis. '
'2021;102:538–43.',
'journal-title': 'Int J Infect Dis'},
{ 'key': '8835_CR18',
'doi-asserted-by': 'publisher',
'first-page': '531',
'DOI': '10.1093/cid/ciaa1176',
'volume': '73',
'author': 'AA Ivashchenko',
'year': '2021',
'unstructured': 'Ivashchenko AA, Dmitriev KA, Vostokova NV, Azarova VN, Blinow AA, '
'Egorova AN, et al. AVIFAVIR for treatment of patients with moderate '
'coronavirus disease 2019 (COVID-19): interim results of a phase ii/iii '
'multicenter randomized clinical trial. Clin Infect Dis. 2021;73:531–4.',
'journal-title': 'Clin Infect Dis'},
{ 'key': '8835_CR19',
'doi-asserted-by': 'crossref',
'unstructured': 'Zhao H, Zhang C, Zhu Q, Chen X, Chen G, Sun W, et al. Favipiravir in the '
'treatment of patients with SARS-CoV-2 RNA recurrent positive after '
'discharge: a multicenter, open-label, randomized trial. Int '
'Immunopharmacol. 2021;97:107702.',
'DOI': '10.1016/j.intimp.2021.107702'},
{ 'key': '8835_CR20',
'doi-asserted-by': 'publisher',
'first-page': '107522',
'DOI': '10.1016/j.intimp.2021.107522',
'volume': '95',
'author': 'M Solaymani-Dodaran',
'year': '2021',
'unstructured': 'Solaymani-Dodaran M, Ghanei M, Bagheri M, Qazvini A, Vahedi E, Hassan '
'Saadat S, et al. Safety and efficacy of Favipiravir in moderate to '
'severe SARS-CoV-2 pneumonia. Int Immunopharmacol. 2021;95:107522.',
'journal-title': 'Int Immunopharmacol'},
{ 'key': '8835_CR21',
'doi-asserted-by': 'publisher',
'first-page': '62',
'DOI': '10.1016/j.ijid.2020.11.142',
'volume': '103',
'author': 'ZF Udwadia',
'year': '2021',
'unstructured': 'Udwadia ZF, Singh P, Barkate H, Patil S, Rangwala S, Pendse A, et al. '
'Efficacy and safety of favipiravir, an oral RNA-dependent RNA polymerase '
'inhibitor, in mild-to-moderate COVID-19: a randomized, comparative, '
'open-label, multicenter, phase 3 clinical trial. Int J Infect Dis. '
'2021;103:62–71.',
'journal-title': 'Int J Infect Dis'},
{ 'issue': '1',
'key': '8835_CR22',
'doi-asserted-by': 'publisher',
'first-page': '4925',
'DOI': '10.1038/s41598-022-08794-w',
'volume': '12',
'author': 'M Al Qahtani',
'year': '2022',
'unstructured': 'Al Qahtani M, Kumar N, Aljawder D, Abdulrahman A, Mohamed MW, Alnashaba '
'F, et al. Randomized controlled trial of favipiravir, '
'hydroxychloroquine, and standard care in patients with mild/moderate '
'COVID-19 disease. Sci Rep. 2022;12(1):4925.',
'journal-title': 'Sci Rep'},
{ 'key': '8835_CR23',
'doi-asserted-by': 'publisher',
'first-page': '3184',
'DOI': '10.1002/jmv.27724',
'volume': '94',
'author': 'M Hassaniazad',
'year': '2022',
'unstructured': 'Hassaniazad M, Farshidi H, Gharibzadeh A, Bazram A, Khalili E, Noormandi '
'A, Fathalipour M. Efficacy and safety of favipiravir plus '
'interferon-beta versus lopinavir/ritonavir plus interferon-beta in '
'moderately ill patients with COVID-19: a randomized clinical trial. J '
'Med Virol. 2022;94:3184–91.',
'journal-title': 'J Med Virol'},
{ 'key': '8835_CR24',
'doi-asserted-by': 'publisher',
'first-page': '101703',
'DOI': '10.1016/j.eclinm.2022.101703',
'volume': '54',
'author': 'JH McMahon',
'year': '2022',
'unstructured': 'McMahon JH, Lau JSY, Coldham A, Roney J, Hagenauer M, Price S, et al. '
'Favipiravir in early symptomatic COVID-19, a randomised '
'placebo-controlled trial. EClinicalMedicine. 2022;54:101703.',
'journal-title': 'EClinicalMedicine'},
{ 'key': '8835_CR25',
'doi-asserted-by': 'publisher',
'first-page': 'e1004120',
'DOI': '10.1371/journal.pmed.1004120',
'volume': '19',
'author': 'DM Lowe',
'year': '2022',
'unstructured': 'Lowe DM, Brown LK, Chowdhury K, Davey S, Yee P, Ikeji F, et al. '
'Favipiravir, lopinavir-ritonavir, or combination therapy (FLARE): a '
'randomised, double-blind, 2 × 2 factorial placebo-controlled trial of '
'early antiviral therapy in COVID-19. PLoS Med. 2022;19:e1004120.',
'journal-title': 'PLoS Med'},
{ 'key': '8835_CR26',
'first-page': 'ciac712',
'volume': '6',
'author': 'Y Golan',
'year': '2022',
'unstructured': 'Golan Y, Campos JAS, Woolson R, Cilla D, Hanabergh R, Gonzales-Rojas Y, '
'et al. Favipiravir in patients with early mild-to-moderate COVID-19: a '
'randomized controlled trial. Clin Infect Dis. 2022;6:ciac712.',
'journal-title': 'Clin Infect Dis.'},
{ 'key': '8835_CR27',
'doi-asserted-by': 'publisher',
'first-page': '602',
'DOI': '10.1016/j.cmi.2021.12.026',
'volume': '28',
'author': 'M Bosaeed',
'year': '2022',
'unstructured': 'Bosaeed M, Alharbi A, Mahmoud E, Alrehily S, Bahlaq M, Gaifer Z, et al. '
'Efficacy of favipiravir in adults with mild COVID-19: a randomized, '
'double-blind, multicentre, placebo-controlled clinical trial. Clin '
'Microbiol Infect. 2022;28:602–8.',
'journal-title': 'Clin Microbiol Infect'},
{ 'key': '8835_CR28',
'doi-asserted-by': 'publisher',
'first-page': 'e432',
'DOI': '10.1093/cid/ciab962',
'volume': '75',
'author': 'CH Chuah',
'year': '2022',
'unstructured': 'Chuah CH, Chow TS, Hor CP, Cheng JT, Ker HB, Lee HG, et al. Efficacy of '
'early treatment with favipiravir on disease progression among high-risk '
'patients with coronavirus disease 2019 (COVID-19): a randomized '
'open-label clinical trial. Clin Infect Dis. 2022;75:e432–9.',
'journal-title': 'Clin Infect Dis'},
{ 'key': '8835_CR29',
'doi-asserted-by': 'publisher',
'first-page': '1883',
'DOI': '10.1093/cid/ciac312',
'volume': '75',
'author': 'M Holubar',
'year': '2022',
'unstructured': 'Holubar M, Subramanian A, Purington N, Hedlin H, Bunning B, Walter KS, '
'et al. Favipiravir for treatment of outpatients with asymptomatic or '
'uncomplicated coronavirus disease 2019: a double-blind, randomized, '
'placebo-controlled, phase 2 trial. Clin Infect Dis. 2022;75:1883–92.',
'journal-title': 'Clin Infect Dis'},
{ 'key': '8835_CR30',
'doi-asserted-by': 'publisher',
'first-page': '37',
'DOI': '10.1002/em.22471',
'volume': '63',
'author': 'MD Waters',
'year': '2022',
'unstructured': 'Waters MD, Warren S, Hughes C, Lewis P, Zhang F. Human genetic risk of '
'treatment with antiviral nucleoside analog drugs that induce lethal '
'mutagenesis: the special case of molnupiravir. Environ Mol Mutagen. '
'2022;63:37–63.',
'journal-title': 'Environ Mol Mutagen'},
{ 'key': '8835_CR31',
'doi-asserted-by': 'publisher',
'unstructured': 'Schilling WHK, Jittamala P, Watson JA, Boyd S, Luvira V, Siripoon T, et '
'al. Antiviral efficacy of molnupiravir versus ritonavir-boosted '
'nirmatrelvir in patients with early symptomatic COVID-19 (PLATCOV): an '
'open-label, phase 2, randomised, controlled, adaptive trial. Lancet '
'Infect Dis. 2023:S1473-3099(23)00493-0. '
'https://doi.org/10.1016/S1473-3099(23)00493-0. Epub ahead of print. '
'Erratum in: Lancet Infect Dis. 2023;23(12):e511.',
'DOI': '10.1016/S1473-3099(23)00493-0'},
{ 'key': '8835_CR32',
'doi-asserted-by': 'publisher',
'first-page': '242',
'DOI': '10.1002/cpt.1844',
'volume': '108',
'author': 'YX Du',
'year': '2020',
'unstructured': 'Du YX, Chen XP. Favipiravir: pharmacokinetics and concerns about '
'clinical trials for 2019-nCoV infection. Clin Pharmacol Ther. '
'2020;108:242–7.',
'journal-title': 'Clin Pharmacol Ther'},
{ 'key': '8835_CR33',
'doi-asserted-by': 'publisher',
'first-page': '509',
'DOI': '10.1056/NEJMoa2116044',
'volume': '386',
'author': 'A Jayk Bernal',
'year': '2022',
'unstructured': 'Jayk Bernal A, Gomes da Silva MM, Musungaie DB, Kovalchuk E, Gonzalez A, '
'Delos Reyes V, et al. Molnupiravir for Oral Treatment of Covid-19 in '
'Nonhospitalized Patients. N Engl J Med. 2022;386:509–20.',
'journal-title': 'N Engl J Med'},
{ 'key': '8835_CR34',
'doi-asserted-by': 'publisher',
'first-page': '1397',
'DOI': '10.1056/NEJMoa2118542',
'volume': '386',
'author': 'J Hammond',
'year': '2022',
'unstructured': 'Hammond J, Leister-Tebbe H, Gardner A, Abreu P, Bao W, Wisemandle W, et '
'al. Oral nirmatrelvir for high-risk, nonhospitalized adults with '
'Covid-19. N Engl J Med. 2022;386:1397–408.',
'journal-title': 'N Engl J Med'},
{ 'key': '8835_CR35',
'doi-asserted-by': 'publisher',
'first-page': 'e0005389',
'DOI': '10.1371/journal.pntd.0005389',
'volume': '11',
'author': 'TH Nguyen',
'year': '2017',
'unstructured': 'Nguyen TH, Guedj J, Anglaret X, Laouénan C, Madelain V, Taburet AM, et '
'al. Favipiravir pharmacokinetics in Ebola-Infected patients of the JIKI '
'trial reveals concentrations lower than targeted. PLoS Negl Trop Dis. '
'2017;11:e0005389.',
'journal-title': 'PLoS Negl Trop Dis'},
{ 'key': '8835_CR36',
'doi-asserted-by': 'publisher',
'unstructured': 'Schilling WHK, Jittamala P, Watson JA, Ekkapongpisit M, Siripoon T, '
'Ngamprasertchai T, et al. Pharmacometrics of high-dose ivermectin in '
'early COVID-19 from an open label, randomized, controlled adaptive '
'platform trial (PLATCOV). Elife. 2023;12:e83201. '
'https://doi.org/10.7554/eLife.83201.',
'DOI': '10.7554/eLife.83201'},
{ 'key': '8835_CR37',
'doi-asserted-by': 'publisher',
'first-page': '1721',
'DOI': '10.1056/NEJMoa2115869',
'volume': '386',
'author': 'G Reis',
'year': '2022',
'unstructured': 'Reis G, Silva EASM, Silva DCM, Thabane L, Milagres AC, Ferreira TS, et '
'al. Effect of early treatment with ivermectin among patients with '
'Covid-19. N Engl J Med. 2022;386:1721–31.',
'journal-title': 'N Engl J Med'},
{ 'issue': '10',
'key': '8835_CR38',
'doi-asserted-by': 'publisher',
'first-page': '1318',
'DOI': '10.1093/infdis/jiad275',
'volume': '228',
'author': 'P Jittamala',
'year': '2023',
'unstructured': 'Jittamala P, Schilling WHK, Watson JA, Luvira V, Siripoon T, '
'Ngamprasertchai T, et al. Clinical antiviral efficacy of remdesivir in '
'COVID-19: an open label, randomized, controlled adaptive platform trial '
'(PLATCOV). J Infect Dis. 2023;228(10):1318–25. '
'https://doi.org/10.1093/infdis/jiad275.',
'journal-title': 'J Infect Dis'},
{ 'key': '8835_CR39',
'doi-asserted-by': 'publisher',
'first-page': '305',
'DOI': '10.1056/NEJMoa2116846',
'volume': '386',
'author': 'RL Gottlieb',
'year': '2022',
'unstructured': 'Gottlieb RL, Vaca CE, Paredes R, Mera J, Webb BJ, Perez G, et al. Early '
'remdesivir to prevent progression to severe Covid-19 in outpatients. N '
'Engl J Med. 2022;386:305–15.',
'journal-title': 'N Engl J Med'},
{ 'key': '8835_CR40',
'doi-asserted-by': 'publisher',
'first-page': '238',
'DOI': '10.1056/NEJMoa2035002',
'volume': '384',
'author': 'DM Weinreich',
'year': '2021',
'unstructured': 'Weinreich DM, Sivapalasingam S, Norton T, Ali S, Gao H, Bhore R, et al. '
'REGN-COV2, a neutralizing antibody cocktail, in outpatients with '
'COVID-19. N Engl J Med. 2021;384:238–51.',
'journal-title': 'N Engl J Med'},
{ 'key': '8835_CR41',
'doi-asserted-by': 'publisher',
'first-page': '1184',
'DOI': '10.1056/NEJMoa2109682',
'volume': '385',
'author': "MP O'Brien",
'year': '2021',
'unstructured': 'O’Brien MP, Forleo-Neto E, Musser BJ, Isa F, Chan KC, Sarkar N, et al. '
'Covid-19 phase 3 prevention trial team. Subcutaneous REGEN-COV antibody '
'combination to prevent Covid-19. N Engl J Med. 2021;385:1184–95.',
'journal-title': 'N Engl J Med.'},
{ 'key': '8835_CR42',
'doi-asserted-by': 'publisher',
'first-page': 'eabl7430',
'DOI': '10.1126/scitranslmed.abl7430',
'volume': '14',
'author': 'WA Fischer 2nd',
'year': '2022',
'unstructured': 'Fischer WA 2nd, Eron JJ Jr, Holman W, Cohen MS, Fang L, Szewczyk LJ, et '
'al. A phase 2a clinical trial of molnupiravir in patients with COVID-19 '
'shows accelerated SARS-CoV-2 RNA clearance and elimination of infectious '
'virus. Sci Transl Med. 2022;14:eabl7430.',
'journal-title': 'Sci Transl Med'},
{ 'key': '8835_CR43',
'doi-asserted-by': 'publisher',
'first-page': '281',
'DOI': '10.1016/S0140-6736(22)02597-1',
'volume': '401',
'author': 'CC Butler',
'year': '2023',
'unstructured': 'Butler CC, Hobbs DR, Gbinigie OA, Rahman NM, Hayward G, Richards DB, et '
'al. Molnupiravir plus usual care versus usual care alone as early '
'treatment for adults with COVID-19 at increased risk of adverse outcomes '
'(PANORAMIC): an open-label, platform-adaptive randomised controlled '
'trial. Lancet. 2023;401:281–93.',
'journal-title': 'Lancet'},
{ 'key': '8835_CR44',
'doi-asserted-by': 'publisher',
'first-page': 'e0019222',
'DOI': '10.1128/aac.00192-22',
'volume': '66',
'author': 'JA Watson',
'year': '2022',
'unstructured': 'Watson JA, Kissler SM, Day NPJ, Grad YH, White NJ. Characterizing '
'SARS-CoV-2 viral clearance kinetics to improve the design of antiviral '
'pharmacometric studies. Antimicrob Agents Chemother. 2022;66:e0019222.',
'journal-title': 'Antimicrob Agents Chemother'}],
'container-title': 'BMC Infectious Diseases',
'original-title': [],
'language': 'en',
'link': [ { 'URL': 'https://link.springer.com/content/pdf/10.1186/s12879-023-08835-3.pdf',
'content-type': 'application/pdf',
'content-version': 'vor',
'intended-application': 'text-mining'},
{ 'URL': 'https://link.springer.com/article/10.1186/s12879-023-08835-3/fulltext.html',
'content-type': 'text/html',
'content-version': 'vor',
'intended-application': 'text-mining'},
{ 'URL': 'https://link.springer.com/content/pdf/10.1186/s12879-023-08835-3.pdf',
'content-type': 'application/pdf',
'content-version': 'vor',
'intended-application': 'similarity-checking'}],
'deposited': { 'date-parts': [[2024, 1, 15]],
'date-time': '2024-01-15T23:01:47Z',
'timestamp': 1705359707000},
'score': 1,
'resource': { 'primary': { 'URL': 'https://bmcinfectdis.biomedcentral.com/articles/10.1186/s12879-023-08835-3'}},
'subtitle': [],
'short-title': [],
'issued': {'date-parts': [[2024, 1, 15]]},
'references-count': 44,
'journal-issue': {'issue': '1', 'published-online': {'date-parts': [[2024, 12]]}},
'alternative-id': ['8835'],
'URL': 'http://dx.doi.org/10.1186/s12879-023-08835-3',
'relation': {},
'ISSN': ['1471-2334'],
'subject': ['Infectious Diseases'],
'container-title-short': 'BMC Infect Dis',
'published': {'date-parts': [[2024, 1, 15]]},
'assertion': [ { 'value': '10 March 2023',
'order': 1,
'name': 'received',
'label': 'Received',
'group': {'name': 'ArticleHistory', 'label': 'Article History'}},
{ 'value': '21 November 2023',
'order': 2,
'name': 'accepted',
'label': 'Accepted',
'group': {'name': 'ArticleHistory', 'label': 'Article History'}},
{ 'value': '15 January 2024',
'order': 3,
'name': 'first_online',
'label': 'First Online',
'group': {'name': 'ArticleHistory', 'label': 'Article History'}},
{'order': 1, 'name': 'Ethics', 'group': {'name': 'EthicsHeading', 'label': 'Declarations'}},
{ 'value': 'All patients provided fully informed written consent. The trial was approved by '
'local and national research ethics boards in Thailand (Faculty of Tropical '
'Medicine Ethics Committee, Mahidol University, FTMEC Ref: TMEC 21–058) and the '
'Central Research Ethics Committee (CREC, Bangkok, Thailand, CREC Ref: '
'CREC048/64BP-MED34), in Brazil by the Research Ethics Committee of the '
'Universidade Federal de Minas Gerais (COEP-UFMG, Minas Gerais, Brazil, '
'COEP-UFMG) and National Research Ethics Commission- (CONEP, Brazil, COEP-UFMG '
'and CONEP Ref: CAAE:51593421.1.0000.5149), and by the Oxford University '
'Tropical Research Ethics Committee (OxTREC, Oxford, UK, OxTREC Ref: 24–21). All '
'methods were performed in accordance with the relevant guidelines and '
'regulations (e.g. Declaration of Helsinki).',
'order': 2,
'name': 'Ethics',
'group': {'name': 'EthicsHeading', 'label': 'Ethics approval and consent to participate'}},
{ 'value': 'Not applicable.',
'order': 3,
'name': 'Ethics',
'group': {'name': 'EthicsHeading', 'label': 'Consent for publication'}},
{ 'value': 'The authors declare no competing interests.',
'order': 4,
'name': 'Ethics',
'group': {'name': 'EthicsHeading', 'label': 'Competing interests'}}],
'article-number': '89'}
