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All Studies   Meta Analysis    Recent:   

The association of antiviral drugs with COVID-19 morbidity: The retrospective analysis of a nationwide COVID-19 cohort

Babayigit et al., Frontiers in Medicine, doi:10.3389/fmed.2022.894126
Aug 2022  
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Ventilation -184% Improvement Relative Risk ICU admission -181% Hospitalization time -100% Favipiravir  Babayigit et al.  LATE TREATMENT Is late treatment with favipiravir beneficial for COVID-19? Retrospective 1,302 patients in Turkey (March - July 2020) Higher ventilation (p=0.011) and ICU admission (p=0.001) c19early.org Babayigit et al., Frontiers in Medicine, Aug 2022 Favorsfavipiravir Favorscontrol 0 0.5 1 1.5 2+
Retrospective 1,472 hospitalized patients in Turkey, showing a higher ICU admission and ventilation with favipiravir. Results may be subject to confounding by indication.
Potential risks include the creation of dangerous variants, and mutagenicity, carcinogenicity, teratogenicity, and embryotoxicity1-5.
This study is excluded in the after exclusion results of meta analysis: substantial unadjusted confounding by indication possible.
Study covers HCQ and favipiravir.
risk of mechanical ventilation, 184.4% higher, RR 2.84, p = 0.01, treatment 47 of 325 (14.5%), control 17 of 977 (1.7%), adjusted per study, odds ratio converted to relative risk, multivariable.
risk of ICU admission, 181.5% higher, RR 2.81, p = 0.001, treatment 75 of 325 (23.1%), control 35 of 969 (3.6%), adjusted per study, odds ratio converted to relative risk, multivariable.
hospitalization time, 100% higher, relative time 2.00, p = 0.001, treatment 265, control 746.
Effect extraction follows pre-specified rules prioritizing more serious outcomes. Submit updates
Babayigit et al., 31 Aug 2022, retrospective, Turkey, peer-reviewed, mean age 51.9, 68 authors, study period 11 March, 2020 - 18 July, 2020. Contact: habayram@ku.edu.tr.
This PaperFavipiravirAll
The association of antiviral drugs with COVID-19 morbidity: The retrospective analysis of a nationwide COVID-19 cohort
Cenk Babayigit, Nurdan Kokturk, Seval Kul, Pelin Duru Cetinkaya, Sibel Atis Nayci, Serap Argun Baris, Oguz Karcioglu, Pinar Aysert, Ilim Irmak, Aycan Akbas Yuksel, Yonca Sekibag, Oya Baydar Toprak, Emel Azak, Sait Mulamahmutoglu, Caglar Cuhadaroglu, Aslihan Demirel, Bugra Kerget, Burcu Baran Ketencioglu, Hasan Selcuk Ozger, Gulcihan Ozkan, Zeynep Ture, Begum Ergan, Vildan Avkan Oguz, Oguz Kilinc, Merve Ercelik, Tansu Ulukavak Ciftci, Ozlem Alici, Esra Nurlu Temel, Ozlem Ataoglu, Asena Aydin, Dilek Cetiner Bahcetepe, Yusuf Taha Gullu, Fusun Fakili, Figen Deveci, Neslihan Kose, Muge Meltem Tor, Gulsah Gunluoglu, Sedat Altin, Teyfik Turgut, Tibel Tuna, Onder Ozturk, Oner Dikensoy, Pinar Yildiz Gulhan, Ilknur Basyigit, Hasim Boyaci, Ipek Kivilcim Oguzulgen, Sermin Borekci, Bilun Gemicioglu, Firat Bayraktar, Osman Elbek, Ismail Hanta, Hacer Kuzu Okur, Gulseren Sagcan, Oguz Uzun, Metin Akgun, Goksel Altinisik, Berna Dursun, Ebru Cakir Edis, Erkmen Gulhan, Fusun Oner Eyuboglu, Okkes Gultekin, Yavuz Havlucu, Metin Ozkan, Aysin Sakar Coskun, Abdullah Sayiner, A Fuat Kalyoncu, Oya Itil, Hasan Bayram
Frontiers in Medicine, doi:10.3389/fmed.2022.894126
Furthermore, favipiravir was associated with increased risks of ICU admission (OR [95% CI]: 3.02 [1.70-5.35]; p = 0.001) and invasive mechanical ventilation requirement (OR [95% CI]: 2.94 [1.28-6.75]; p = 0.011). Conclusion: Our findings demonstrated that antiviral drugs including lopinavir, ritonavir, and favipiravir were associated with negative clinical outcomes such as increased risks for lengthy hospital stay, ICU admission, and invasive mechanical ventilation requirement. Therefore, repurposing such agents without proven clinical evidence might not be the best approach for COVID-19 treatment.
Ethics statement The studies involving human participants were reviewed and approved by Institutional Review Board of Gazi University Faculty of Medicine, Ankara, Turkey (356/22.05.2020). Written informed consent for participation was not required for this study in accordance with the national legislation and the institutional requirements. Author contributions CB, NKk, HBa, OI, FO, AS, ASC, BD, and AK designed the study. CB, NKk, PC, SAB, OKa, PA, II, AAk, YS, OB, EA, SM, CC, AD, BK, BB, HO, GO, ZT, BE, VA, OKi, ME, TU, OAl, EN, OAt, AAy, DC, YG, FF, FD, NKs, MT, GG, SA, TeT, TiT, OO, OD, PY, IB, HBo, IO, SB, BG, FB, OE, IH, HK, GS, OU, MA, GA, BD, EC, EG, OG, YH, MO, and ASC collected the data. SK and SAN analyzed the data. CB, NKk, SK, and HBa searched the literature and wrote the manuscript. CB, NKk, SK, SAB, PC, and HBa edited and revised manuscript according to journal's instructions. CB, NKk, SK, PC, SAB, and HBa edited and controlled the final version of the manuscript. All authors approved the final version of the manuscript. Conflict of interest The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The reviewer BH declared a shared affiliation with the authors, II and AK to the handling editor at the time of review. Publisher's note All claims expressed in this article are solely those of the authors and do not necessarily represent those of..
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{ 'indexed': {'date-parts': [[2022, 8, 31]], 'date-time': '2022-08-31T07:42:07Z', 'timestamp': 1661931727547}, 'reference-count': 52, 'publisher': 'Frontiers Media SA', 'license': [ { 'start': { 'date-parts': [[2022, 8, 31]], 'date-time': '2022-08-31T00:00:00Z', 'timestamp': 1661904000000}, 'content-version': 'vor', 'delay-in-days': 0, 'URL': 'https://creativecommons.org/licenses/by/4.0/'}], 'content-domain': {'domain': ['frontiersin.org'], 'crossmark-restriction': True}, 'abstract': '<jats:sec><jats:title>Background and objectives</jats:title><jats:p>Although several ' 'repurposed antiviral drugs have been used for the treatment of COVID-19, only a few such as ' 'remdesivir and molnupiravir have shown promising effects. The objectives of our study were to ' 'investigate the association of repurposed antiviral drugs with COVID-19 ' 'morbidity.</jats:p></jats:sec><jats:sec><jats:title>Methods</jats:title><jats:p>Patients ' 'admitted to 26 different hospitals located in 16 different provinces between March 11–July ' '18, 2020, were enrolled. Case definition was based on WHO criteria. Patients were managed ' 'according to the guidelines by Scientific Board of Ministry of Health of Turkey. Primary ' 'outcomes were length of hospitalization, intensive care unit (ICU) requirement, and ' 'intubation.</jats:p></jats:sec><jats:sec><jats:title>Results</jats:title><jats:p>We ' 'retrospectively evaluated 1,472 COVID-19 adult patients; 57.1% were men (mean age = 51.9 ± ' '17.7years). A total of 210 (14.3%) had severe pneumonia, 115 (7.8%) were admitted to ICUs, ' 'and 69 (4.7%) were intubated during hospitalization. The median (interquartile range) of ' 'duration of hospitalization, including ICU admission, was 7 (5–12) days. Favipiravir ' '(<jats:italic>n</jats:italic> = 328), lopinavir/ritonavir (<jats:italic>n</jats:italic> = ' '55), and oseltamivir (<jats:italic>n</jats:italic> = 761) were administered as antiviral ' 'agents, and hydroxychloroquine (HCQ, <jats:italic>n</jats:italic> = 1,382) and azithromycin ' '(<jats:italic>n</jats:italic> = 738) were used for their immunomodulatory activity. ' 'Lopinavir/ritonavir (β [95% CI]: 4.71 [2.31–7.11]; <jats:italic>p</jats:italic> = 0.001), ' 'favipiravir (β [95% CI]: 3.55 [2.56–4.55]; <jats:italic>p</jats:italic> = 0.001) and HCQ (β ' '[95% CI]: 0.84 [0.02–1.67]; <jats:italic>p</jats:italic> = 0.046) were associated with ' 'increased risk of lengthy hospital stays. Furthermore, favipiravir was associated with ' 'increased risks of ICU admission (OR [95% CI]: 3.02 [1.70–5.35]; <jats:italic>p</jats:italic> ' '= 0.001) and invasive mechanical ventilation requirement (OR [95% CI]: 2.94 [1.28–6.75]; ' '<jats:italic>p</jats:italic> = ' '0.011).</jats:p></jats:sec><jats:sec><jats:title>Conclusion</jats:title><jats:p>Our findings ' 'demonstrated that antiviral drugs including lopinavir, ritonavir, and favipiravir were ' 'associated with negative clinical outcomes such as increased risks for lengthy hospital stay, ' 'ICU admission, and invasive mechanical ventilation requirement. Therefore, repurposing such ' 'agents without proven clinical evidence might not be the best approach for COVID-19 ' 'treatment.</jats:p></jats:sec>', 'DOI': '10.3389/fmed.2022.894126', 'type': 'journal-article', 'created': {'date-parts': [[2022, 8, 31]], 'date-time': '2022-08-31T06:59:23Z', 'timestamp': 1661929163000}, 'update-policy': 'http://dx.doi.org/10.3389/crossmark-policy', 'source': 'Crossref', 'is-referenced-by-count': 0, 'title': 'The association of antiviral drugs with COVID-19 morbidity: The retrospective analysis of a ' 'nationwide COVID-19 cohort', 'prefix': '10.3389', 'volume': '9', 'author': [ {'given': 'Cenk', 'family': 'Babayigit', 'sequence': 'first', 'affiliation': []}, {'given': 'Nurdan', 'family': 'Kokturk', 'sequence': 'additional', 'affiliation': []}, {'given': 'Seval', 'family': 'Kul', 'sequence': 'additional', 'affiliation': []}, {'given': 'Pelin Duru', 'family': 'Cetinkaya', 'sequence': 'additional', 'affiliation': []}, {'given': 'Sibel', 'family': 'Atis 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A European league ' 'against rheumatism/American College of rheumatology/paediatric ' 'rheumatology international trials organisation collaborative ' 'initiative.', 'volume': '75', 'author': 'Ravelli', 'year': '2016', 'journal-title': 'Ann Rheum Dis.'}, { 'key': 'B17', 'doi-asserted-by': 'publisher', 'first-page': '112', 'DOI': '10.15420/ecr.2017:16:1', 'article-title': 'QT prolongation and malignant arrhythmia: How serious a problem?', 'volume': '12', 'author': 'Antoniou', 'year': '2017', 'journal-title': 'Eur Cardiol.'}, { 'key': 'B18', 'doi-asserted-by': 'publisher', 'first-page': '269', 'DOI': '10.1038/s41422-020-0282-0', 'article-title': 'Remdesivir and chloroquine effectively inhibit the recently emerged ' 'novel coronavirus (2019-nCoV) in vitro.', 'volume': '30', 'author': 'Wang', 'year': '2020', 'journal-title': 'Cell Res.'}, { 'key': 'B19', 'doi-asserted-by': 'publisher', 'first-page': '72', '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.', 'volume': '14', 'author': 'Gao', 'year': '2020', 'journal-title': 'Biosci Trends.'}, { 'key': 'B20', 'doi-asserted-by': 'publisher', 'first-page': '1087', 'DOI': '10.1097/CM9.0000000000000819', 'article-title': 'Diagnosis and treatment protocol for novel coronavirus pneumonia (trial ' 'version 7).', 'volume': '133', 'author': 'Wei', 'year': '2020', 'journal-title': 'Chin Med J.'}, { 'key': 'B21', 'year': '2020', 'journal-title': 'Coronavirus (covid-19) update: FDA revokes emergency use authorization ' 'for chloroquine and hydroxychloroquine.'}, { 'key': 'B22', 'doi-asserted-by': 'publisher', 'first-page': '497', 'DOI': '10.1056/NEJMoa2023184', 'article-title': 'Repurposed antiviral drugs for covid-19 – interim WHO solidarity trial ' 'results.', 'volume': '384', 'author': 'Pan', 'year': '2021', 'journal-title': 'N Engl J Med.'}, { 'key': 'B23', 'doi-asserted-by': 'publisher', 'first-page': '2041', 'DOI': '10.1056/NEJMx200021', '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': 'B24', 'doi-asserted-by': 'publisher', 'first-page': '19', 'DOI': '10.1016/j.cmi.2020.08.022', 'article-title': 'Effect of hydroxychloroquine with or without azithromycin on the ' 'mortality of coronavirus disease 2019 (COVID-19) patients: A systematic ' 'review and meta-analysis.', 'volume': '27', 'author': 'Fiolet', 'year': '2021', 'journal-title': 'Clin Microbiol Infect.'}, { 'key': 'B25', 'doi-asserted-by': 'publisher', 'first-page': '959', 'DOI': '10.1016/S0140-6736(20)31862-6', 'article-title': 'Azithromycin in addition to standard of care versus standard of care ' 'alone in the treatment of patients admitted to the hospital with severe ' 'COVID-19 in Brazil (COALITION II): A randomised clinical trial.', 'volume': '396', 'author': 'Furtado', 'year': '2020', 'journal-title': 'Lancet.'}, { 'key': 'B26', 'doi-asserted-by': 'publisher', 'first-page': '1885', 'DOI': '10.2165/11204950-000000000-00000', 'article-title': 'Lopinavir/Ritonavir: A review of its use in the management of HIV-1 ' 'infection.', 'volume': '70', 'author': 'Croxtall', 'year': '2010', 'journal-title': 'Drugs.'}, { 'key': 'B27', 'doi-asserted-by': 'publisher', 'first-page': '9133', 'DOI': '10.1002/jcp.29785', 'article-title': 'A global treatment for coronaviruses including COVID-19.', 'volume': '235', 'author': 'Yousefi', 'year': '2020', 'journal-title': 'J Cell Physiol.'}, { 'key': 'B28', 'first-page': '399', 'article-title': 'Treatment of severe acute respiratory syndrome with ' 'lopinavir/ritonavir: A multicentre retrospective matched cohort study.', 'volume': '9', 'author': 'Chan', 'year': '2003', 'journal-title': 'Hong Kong Med J.'}, { 'key': 'B29', 'doi-asserted-by': 'publisher', 'DOI': '10.1016/j.antiviral.2020.104786', 'article-title': 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'10.1007/s00705-021-04956-9', 'article-title': 'Efficacy of favipiravir in COVID-19 treatment: A multi-center ' 'randomized study.', 'volume': '166', 'author': 'Dabbous', 'year': '2021', 'journal-title': 'Arch Virol.'}, { 'key': 'B37', 'doi-asserted-by': 'publisher', 'first-page': '2575', 'DOI': '10.1007/s10096-021-04307-1', 'article-title': 'Effectiveness of favipiravir in COVID-19: A live systematic review.', 'volume': '40', 'author': 'Özlüşen', 'year': '2021', 'journal-title': 'Eur J Clin Microbiol Infect Dis.'}, { 'key': 'B38', 'doi-asserted-by': 'publisher', 'first-page': '365', 'DOI': '10.1016/j.jiph.2020.12.017', 'article-title': 'Comparing ICU admission rates of mild/moderate COVID-19 patients ' 'treated with hydroxychloroquine, favipiravir, and hydroxychloroquine ' 'plus favipiravir.', 'volume': '14', 'author': 'Guner', 'year': '2021', 'journal-title': 'J Infect Public Health.'}, { 'key': 'B39', 'doi-asserted-by': 'publisher', 'first-page': '119', 'DOI': '10.14744/nci.2021.60420', 'article-title': 'ICU admission rates in Istanbul following the addition of favipiravir ' 'to the national COVID-19 treatment protocol.', 'volume': '8', 'author': 'Guner', 'year': '2021', 'journal-title': 'North Clin Istanb.'}, { 'key': 'B40', 'doi-asserted-by': 'publisher', 'first-page': '45', 'DOI': '10.1016/S2055-6640(20)30016-9', 'article-title': 'A review of the safety of favipiravir – a potential treatment in the ' 'COVID-19 pandemic?', 'volume': '6', 'author': 'Pilkington', 'year': '2020', 'journal-title': 'J Virus Erad.'}, { 'key': 'B41', 'doi-asserted-by': 'publisher', 'first-page': '501', 'DOI': '10.1016/j.ijid.2020.10.069', 'article-title': 'Role of favipiravir in the treatment of COVID-19.', 'volume': '102', 'author': 'Joshi', 'year': '2021', 'journal-title': 'Int J Infect Dis.'}, { 'key': 'B42', 'doi-asserted-by': 'publisher', 'DOI': '10.1371/journal.pntd.0006034', 'article-title': 'Qtc interval prolongation during favipiravir therapy in an ' 'ebolavirus-infected patient.', 'volume': '11', 'author': 'Chinello', 'year': '2017', 'journal-title': 'PLoS Negl Trop Dis.'}, { 'key': 'B43', 'doi-asserted-by': 'publisher', 'first-page': '215', 'DOI': '10.1177/2048872620922784', 'article-title': 'Cardiac safety of off-label COVID-19 drug therapy: A review and ' 'proposed monitoring protocol.', 'volume': '9', 'author': 'Naksuk', 'year': '2020', 'journal-title': 'Eur Heart J Acute Cardiovasc Care.'}, { 'key': 'B44', 'doi-asserted-by': 'publisher', 'first-page': '791', 'DOI': '10.1002/cpt.1866', 'article-title': 'Incidence of adverse drug reactions in COVID-19 patients in China: An ' 'active monitoring study by hospital pharmacovigilance system.', 'volume': '108', 'author': 'Sun', 'year': '2020', 'journal-title': 'Clin Pharmacol Ther.'}, { 'key': 'B45', 'year': '2020', 'journal-title': 'FDA approves first treatment for COVID-19.'}, { 'key': 'B46', 'doi-asserted-by': 'publisher', 'first-page': '1048', 'DOI': '10.1001/jama.2020.16349', 'article-title': 'Effect of remdesivir vs standard care on clinical status at 11 days in ' 'patients with moderate COVID-19: A Randomized clinical trial.', 'volume': '324', 'author': 'Spinner', 'year': '2020', 'journal-title': 'JAMA.'}, { 'key': 'B47', 'doi-asserted-by': 'publisher', 'first-page': '209', 'DOI': '10.7326/M20-5752', 'article-title': 'Remdesivir for adults with COVID-19: A living systematic review for an ' 'American college of physicians practice points.', 'volume': '174', 'author': 'Wit', 'year': '2021', 'journal-title': 'Ann Intern Med.'}, { 'key': 'B48', 'doi-asserted-by': 'publisher', 'first-page': '1813', 'DOI': '10.1056/NEJMoa2007764', 'article-title': 'Remdesivir for the treatment of Covid-19-final report.', 'volume': '383', 'author': 'Beigel', 'year': '2020', 'journal-title': 'N Engl J Med.'}, { 'key': 'B49', 'doi-asserted-by': 'publisher', 'first-page': '509', 'DOI': '10.1056/NEJMoa2116044', 'article-title': 'Molnupiravir for oral treatment of Covid-19 in nonhospitalized ' 'patients.', 'volume': '386', 'author': 'Jayk Bernal', 'year': '2022', 'journal-title': 'N Engl J Med.'}, { 'key': 'B50', 'year': '2021', 'journal-title': 'Coronavirus (COVID-19) update: FDA Authorizes additional oral antiviral ' 'for treatment of COVID-19 in certain adults.'}, { 'key': 'B51', 'doi-asserted-by': 'publisher', 'DOI': '10.3390/vaccines9111317', 'article-title': 'Coronavirus disease (COVID-19) control between drug repurpising and ' 'vaccination: A comprehensive overview.', 'volume': '9', 'author': 'Al-Karmalawy', 'year': '2021', 'journal-title': 'Vaccines.'}, { 'key': 'B52', 'doi-asserted-by': 'publisher', 'first-page': '787', 'DOI': '10.1513/AnnalsATS.202004-325IP', 'article-title': 'In defence of evidence-based medicine for the treatment of COVID-19 ' 'acute respiratory distress syndrome.', 'volume': '17', 'author': 'Rice', 'year': '2020', 'journal-title': 'Ann Am Thorac Soc.'}], 'container-title': 'Frontiers in Medicine', 'original-title': [], 'link': [ { 'URL': 'https://www.frontiersin.org/articles/10.3389/fmed.2022.894126/full', 'content-type': 'unspecified', 'content-version': 'vor', 'intended-application': 'similarity-checking'}], 'deposited': { 'date-parts': [[2022, 8, 31]], 'date-time': '2022-08-31T06:59:31Z', 'timestamp': 1661929171000}, 'score': 1, 'resource': {'primary': {'URL': 'https://www.frontiersin.org/articles/10.3389/fmed.2022.894126/full'}}, 'subtitle': [], 'short-title': [], 'issued': {'date-parts': [[2022, 8, 31]]}, 'references-count': 52, 'alternative-id': ['10.3389/fmed.2022.894126'], 'URL': 'http://dx.doi.org/10.3389/fmed.2022.894126', 'relation': {}, 'ISSN': ['2296-858X'], 'subject': ['General Medicine'], 'container-title-short': 'Front. Med.', 'published': {'date-parts': [[2022, 8, 31]]}}
Late treatment
is less effective
Please send us corrections, updates, or comments. c19early involves the extraction of 100,000+ datapoints from thousands of papers. Community updates help ensure high accuracy. Treatments and other interventions are complementary. All practical, effective, and safe means should be used based on risk/benefit analysis. No treatment or intervention is 100% available and effective for all current and future variants. We do not provide medical advice. Before taking any medication, consult a qualified physician who can provide personalized advice and details of risks and benefits based on your medical history and situation. FLCCC and WCH provide treatment protocols.
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