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Published in: European Journal of Clinical Microbiology & Infectious Diseases 12/2021

01-12-2021 | COVID-19 | Original Article

Effectiveness of favipiravir in COVID-19: a live systematic review

Authors: Batu Özlüşen, Şima Kozan, Rüştü Emre Akcan, Mekselina Kalender, Doğukan Yaprak, İbrahim Batuhan Peltek, Şiran Keske, Mehmet Gönen, Önder Ergönül

Published in: European Journal of Clinical Microbiology & Infectious Diseases | Issue 12/2021

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Abstract

We performed a systematic review and meta-analysis for the effectiveness of Favipiravir on the fatality and the requirement of mechanical ventilation for the treatment of moderate to severe COVID-19 patients. We searched available literature and reported it by using PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. Until June 1, 2021, we searched PubMed, bioRxiv, medRxiv, ClinicalTrials.gov, Cochrane Central Register of Controlled Trials (CENTRAL), and Google Scholar by using the keywords “Favipiravir” and terms synonymous with COVID-19. Studies for Favipiravir treatment compared to standard of care among moderate and severe COVID-19 patients were included. Risk of bias assessment was performed using Revised Cochrane risk of bias tool for randomized trials (RoB 2) and ROBINS-I assessment tool for non-randomized studies. We defined the outcome measures as fatality and requirement for mechanical ventilation. A total of 2702 studies were identified and 12 clinical trials with 1636 patients were analyzed. Nine out of 12 studies were randomized controlled trials. Among the randomized studies, one study has low risk of bias, six studies have moderate risk of bias, and 2 studies have high risk of bias. Observational studies were identified as having moderate risk of bias and non-randomized study was found to have serious risk of bias. Our meta-analysis did not reveal any significant difference between the intervention and the comparator on fatality rate (OR 1.11, 95% CI 0.64–1.94) and mechanical ventilation requirement (OR 0.50, 95% CI 0.13–1.95). There is no significant difference in fatality rate and mechanical ventilation requirement between Favipiravir treatment and the standard of care in moderate and severe COVID-19 patients.
Literature
1.
go back to reference Consortium WHOST, Pan H, Peto R, Henao-Restrepo AM, Preziosi MP, Sathiyamoorthy V, Abdool Karim Q, Alejandria MM, Hernandez Garcia C, Kieny MP, Malekzadeh R, Murthy S, Reddy KS, Roses Periago M, Abi Hanna P, Ader F, Al-Bader AM, Alhasawi A, Allum E, Alotaibi A, Alvarez-Moreno CA, Appadoo S, Asiri A, Aukrust P, Barratt-Due A, Bellani S, Branca M, Cappel-Porter HBC, Cerrato N, Chow TS, Como N, Eustace J, Garcia PJ, Godbole S, Gotuzzo E, Griskevicius L, Hamra R, Hassan M, Hassany M, Hutton D, Irmansyah I, Jancoriene L, Kirwan J, Kumar S, Lennon P, Lopardo G, Lydon P, Magrini N, Maguire T, Manevska S, Manuel O, McGinty S, Medina MT, Mesa Rubio ML, Miranda-Montoya MC, Nel J, Nunes EP, Perola M, Portoles A, Rasmin MR, Raza A, Rees H, Reges PPS, Rogers CA, Salami K, Salvadori MI, Sinani N, Sterne JAC, Stevanovikj M, Tacconelli E, Tikkinen KAO, Trelle S, Zaid H, Rottingen JA, Swaminathan S (2020) Repurposed Antiviral Drugs for Covid-19 - Interim WHO Solidarity Trial Results. N Engl J Med. https://doi.org/10.1056/NEJMoa2023184CrossRef Consortium WHOST, Pan H, Peto R, Henao-Restrepo AM, Preziosi MP, Sathiyamoorthy V, Abdool Karim Q, Alejandria MM, Hernandez Garcia C, Kieny MP, Malekzadeh R, Murthy S, Reddy KS, Roses Periago M, Abi Hanna P, Ader F, Al-Bader AM, Alhasawi A, Allum E, Alotaibi A, Alvarez-Moreno CA, Appadoo S, Asiri A, Aukrust P, Barratt-Due A, Bellani S, Branca M, Cappel-Porter HBC, Cerrato N, Chow TS, Como N, Eustace J, Garcia PJ, Godbole S, Gotuzzo E, Griskevicius L, Hamra R, Hassan M, Hassany M, Hutton D, Irmansyah I, Jancoriene L, Kirwan J, Kumar S, Lennon P, Lopardo G, Lydon P, Magrini N, Maguire T, Manevska S, Manuel O, McGinty S, Medina MT, Mesa Rubio ML, Miranda-Montoya MC, Nel J, Nunes EP, Perola M, Portoles A, Rasmin MR, Raza A, Rees H, Reges PPS, Rogers CA, Salami K, Salvadori MI, Sinani N, Sterne JAC, Stevanovikj M, Tacconelli E, Tikkinen KAO, Trelle S, Zaid H, Rottingen JA, Swaminathan S (2020) Repurposed Antiviral Drugs for Covid-19 - Interim WHO Solidarity Trial Results. N Engl J Med. https://​doi.​org/​10.​1056/​NEJMoa2023184CrossRef
5.
go back to reference Sterne JAC, Savovic J, Page MJ, Elbers RG, Blencowe NS, Boutron I, Cates CJ, Cheng HY, Corbett MS, Eldridge SM, Emberson JR, Hernan MA, Hopewell S, Hrobjartsson A, Junqueira DR, Juni P, Kirkham JJ, Lasserson T, Li T, McAleenan A, Reeves BC, Shepperd S, Shrier I, Stewart LA, Tilling K, White IR, Whiting PF, Higgins JPT (2019) RoB 2: a revised tool for assessing risk of bias in randomised trials. BMJ 366:l4898. https://doi.org/10.1136/bmj.l4898CrossRefPubMed Sterne JAC, Savovic J, Page MJ, Elbers RG, Blencowe NS, Boutron I, Cates CJ, Cheng HY, Corbett MS, Eldridge SM, Emberson JR, Hernan MA, Hopewell S, Hrobjartsson A, Junqueira DR, Juni P, Kirkham JJ, Lasserson T, Li T, McAleenan A, Reeves BC, Shepperd S, Shrier I, Stewart LA, Tilling K, White IR, Whiting PF, Higgins JPT (2019) RoB 2: a revised tool for assessing risk of bias in randomised trials. BMJ 366:l4898. https://​doi.​org/​10.​1136/​bmj.​l4898CrossRefPubMed
6.
go back to reference Sterne JA, Hernan MA, Reeves BC, Savovic J, Berkman ND, Viswanathan M, Henry D, Altman DG, Ansari MT, Boutron I, Carpenter JR, Chan AW, Churchill R, Deeks JJ, Hrobjartsson A, Kirkham J, Juni P, Loke YK, Pigott TD, Ramsay CR, Regidor D, Rothstein HR, Sandhu L, Santaguida PL, Schunemann HJ, Shea B, Shrier I, Tugwell P, Turner L, Valentine JC, Waddington H, Waters E, Wells GA, Whiting PF, Higgins JP (2016) ROBINS-I: a tool for assessing risk of bias in non-randomised studies of interventions. BMJ 355:i4919. https://doi.org/10.1136/bmj.i4919CrossRefPubMedPubMedCentral Sterne JA, Hernan MA, Reeves BC, Savovic J, Berkman ND, Viswanathan M, Henry D, Altman DG, Ansari MT, Boutron I, Carpenter JR, Chan AW, Churchill R, Deeks JJ, Hrobjartsson A, Kirkham J, Juni P, Loke YK, Pigott TD, Ramsay CR, Regidor D, Rothstein HR, Sandhu L, Santaguida PL, Schunemann HJ, Shea B, Shrier I, Tugwell P, Turner L, Valentine JC, Waddington H, Waters E, Wells GA, Whiting PF, Higgins JP (2016) ROBINS-I: a tool for assessing risk of bias in non-randomised studies of interventions. BMJ 355:i4919. https://​doi.​org/​10.​1136/​bmj.​i4919CrossRefPubMedPubMedCentral
9.
go back to reference Khamis F, Al Naabi H, Al Lawati A, Ambusaidi Z, Al Sharji M, Al Barwani U, Pandak N, Al Balushi Z, Al Bahrani M, Al Salami I, Al-Zakwani I (2021) 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 102:538–543. https://doi.org/10.1016/j.ijid.2020.11.008CrossRefPubMed Khamis F, Al Naabi H, Al Lawati A, Ambusaidi Z, Al Sharji M, Al Barwani U, Pandak N, Al Balushi Z, Al Bahrani M, Al Salami I, Al-Zakwani I (2021) 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 102:538–543. https://​doi.​org/​10.​1016/​j.​ijid.​2020.​11.​008CrossRefPubMed
14.
go back to reference Alamer A, Alrashed AA, Alfaifi M, Alosaimi B, AlHassar F, Almutairi M, Howaidi J, Almutairi W, Mohzari Y, Sulaiman T, Al-Jedai A, Alajami HN, Alkharji F, Alsaeed A, Alali AH, Baredhwan AA, Abraham I, Almulhim AS (2021) Effectiveness and safety of favipiravir compared to supportive care in moderately to critically ill COVID-19 patients: a retrospective study with propensity score matching sensitivity analysis. Curr Med Res Opin:1–13. https://doi.org/10.1080/03007995.2021.1920900 Alamer A, Alrashed AA, Alfaifi M, Alosaimi B, AlHassar F, Almutairi M, Howaidi J, Almutairi W, Mohzari Y, Sulaiman T, Al-Jedai A, Alajami HN, Alkharji F, Alsaeed A, Alali AH, Baredhwan AA, Abraham I, Almulhim AS (2021) Effectiveness and safety of favipiravir compared to supportive care in moderately to critically ill COVID-19 patients: a retrospective study with propensity score matching sensitivity analysis. Curr Med Res Opin:1–13. https://​doi.​org/​10.​1080/​03007995.​2021.​1920900
17.
go back to reference Szabo BG, Lenart KS, Petrik B, Gaspar Z, Balogh Z, Banyai Z, Banyasz E, Budai J, Czel E, Fried K, Hanuska A, Kiss-Dala N, Lorinczi C, Nemesi K, Kadar J, Nagy EL, Osvald A, Petrovicz E, Riczu A, Szanka J, Szathmary B, Szombati A, Toth S, Varnai Z, Woller O, Szlavik J, Lakatos B (2020) Role of favipiravir in the treatment of adult patients with moderate to severe COVID-19: a single-center, prospective, observational, sequential cohort study from Hungary. medRxiv:2020.2011.2026.20238014. https://doi.org/10.1101/2020.11.26.20238014 Szabo BG, Lenart KS, Petrik B, Gaspar Z, Balogh Z, Banyai Z, Banyasz E, Budai J, Czel E, Fried K, Hanuska A, Kiss-Dala N, Lorinczi C, Nemesi K, Kadar J, Nagy EL, Osvald A, Petrovicz E, Riczu A, Szanka J, Szathmary B, Szombati A, Toth S, Varnai Z, Woller O, Szlavik J, Lakatos B (2020) Role of favipiravir in the treatment of adult patients with moderate to severe COVID-19: a single-center, prospective, observational, sequential cohort study from Hungary. medRxiv:2020.2011.2026.20238014. https://​doi.​org/​10.​1101/​2020.​11.​26.​20238014
18.
go back to reference Cai Q, Yang M, Liu D, Chen J, Shu D, Xia J, Liao X, Gu Y, Cai Q, Yang Y, Shen C, Li X, Peng L, Huang D, Zhang J, Zhang S, Wang F, Liu J, Chen L, Chen S, Wang Z, Zhang Z, Cao R, Zhong W, Liu Y, Liu L (2020) Experimental treatment with favipiravir for COVID-19: an open-label control study. Engineering (Beijing) 6(10):1192–1198. https://doi.org/10.1016/j.eng.2020.03.007CrossRef Cai Q, Yang M, Liu D, Chen J, Shu D, Xia J, Liao X, Gu Y, Cai Q, Yang Y, Shen C, Li X, Peng L, Huang D, Zhang J, Zhang S, Wang F, Liu J, Chen L, Chen S, Wang Z, Zhang Z, Cao R, Zhong W, Liu Y, Liu L (2020) Experimental treatment with favipiravir for COVID-19: an open-label control study. Engineering (Beijing) 6(10):1192–1198. https://​doi.​org/​10.​1016/​j.​eng.​2020.​03.​007CrossRef
20.
go back to reference Tang W, Cao Z, Han M, Wang Z, Chen J, Sun W, Wu Y, Xiao W, Liu S, Chen E, Chen W, Wang X, Yang J, Lin J, Zhao Q, Yan Y, Xie Z, Li D, Yang Y, Liu L, Qu J, Ning G, Shi G, Xie Q (2020) Hydroxychloroquine in patients with mainly mild to moderate coronavirus disease 2019: open label, randomised controlled trial. BMJ 369:m1849. https://doi.org/10.1136/bmj.m1849CrossRefPubMedPubMedCentral Tang W, Cao Z, Han M, Wang Z, Chen J, Sun W, Wu Y, Xiao W, Liu S, Chen E, Chen W, Wang X, Yang J, Lin J, Zhao Q, Yan Y, Xie Z, Li D, Yang Y, Liu L, Qu J, Ning G, Shi G, Xie Q (2020) Hydroxychloroquine in patients with mainly mild to moderate coronavirus disease 2019: open label, randomised controlled trial. BMJ 369:m1849. https://​doi.​org/​10.​1136/​bmj.​m1849CrossRefPubMedPubMedCentral
22.
go back to reference Cao B, Wang Y, Wen D, Liu W, Wang J, Fan G, Ruan L, Song B, Cai Y, Wei M, Li X, Xia J, Chen N, Xiang J, Yu T, Bai T, Xie X, Zhang L, Li C, Yuan Y, Chen H, Li H, Huang H, Tu S, Gong F, Liu Y, Wei Y, Dong C, Zhou F, Gu X, Xu J, Liu Z, Zhang Y, Li H, Shang L, Wang K, Li K, Zhou X, Dong X, Qu Z, Lu S, Hu X, Ruan S, Luo S, Wu J, Peng L, Cheng F, Pan L, Zou J, Jia C, Wang J, Liu X, Wang S, Wu X, Ge Q, He J, Zhan H, Qiu F, Guo L, Huang C, Jaki T, Hayden FG, Horby PW, Zhang D, Wang C (2020) A trial of lopinavir–ritonavir in adults hospitalized with severe Covid-19. N Engl J Med 382(19):1787–1799. https://doi.org/10.1056/NEJMoa2001282CrossRefPubMed Cao B, Wang Y, Wen D, Liu W, Wang J, Fan G, Ruan L, Song B, Cai Y, Wei M, Li X, Xia J, Chen N, Xiang J, Yu T, Bai T, Xie X, Zhang L, Li C, Yuan Y, Chen H, Li H, Huang H, Tu S, Gong F, Liu Y, Wei Y, Dong C, Zhou F, Gu X, Xu J, Liu Z, Zhang Y, Li H, Shang L, Wang K, Li K, Zhou X, Dong X, Qu Z, Lu S, Hu X, Ruan S, Luo S, Wu J, Peng L, Cheng F, Pan L, Zou J, Jia C, Wang J, Liu X, Wang S, Wu X, Ge Q, He J, Zhan H, Qiu F, Guo L, Huang C, Jaki T, Hayden FG, Horby PW, Zhang D, Wang C (2020) A trial of lopinavir–ritonavir in adults hospitalized with severe Covid-19. N Engl J Med 382(19):1787–1799. https://​doi.​org/​10.​1056/​NEJMoa2001282CrossRefPubMed
23.
go back to reference Li Y, Xie Z, Lin W, Cai W, Wen C, Guan Y, Mo X, Wang J, Wang Y, Peng P, Chen X, Hong W, Xiao G, Liu J, Zhang L, Hu F, Li F, Zhang F, Deng X, Li L (2020) Efficacy and safety of lopinavir/ritonavir or arbidol in adult patients with mild/moderate COVID-19: an exploratory randomized controlled trial. Med 1(1):105-113.e104. https://doi.org/10.1016/j.medj.2020.04.001CrossRefPubMed Li Y, Xie Z, Lin W, Cai W, Wen C, Guan Y, Mo X, Wang J, Wang Y, Peng P, Chen X, Hong W, Xiao G, Liu J, Zhang L, Hu F, Li F, Zhang F, Deng X, Li L (2020) Efficacy and safety of lopinavir/ritonavir or arbidol in adult patients with mild/moderate COVID-19: an exploratory randomized controlled trial. Med 1(1):105-113.e104. https://​doi.​org/​10.​1016/​j.​medj.​2020.​04.​001CrossRefPubMed
31.
Metadata
Title
Effectiveness of favipiravir in COVID-19: a live systematic review
Authors
Batu Özlüşen
Şima Kozan
Rüştü Emre Akcan
Mekselina Kalender
Doğukan Yaprak
İbrahim Batuhan Peltek
Şiran Keske
Mehmet Gönen
Önder Ergönül
Publication date
01-12-2021
Publisher
Springer Berlin Heidelberg
Keyword
COVID-19
Published in
European Journal of Clinical Microbiology & Infectious Diseases / Issue 12/2021
Print ISSN: 0934-9723
Electronic ISSN: 1435-4373
DOI
https://doi.org/10.1007/s10096-021-04307-1

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