key: cord-0868038-yviywu2f authors: SZABO, B. G.; LENART, K. S.; 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, E. L.; OSVALD, A.; PETROVICZ, E.; RICZU, A.; SZANKA, J.; SZATHMARY, B.; SZOMBATI, A.; TOTH, S.; VARNAI, Z.; WOLLER, O.; SZLAVIK, J.; LAKATOS, B. title: 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 date: 2020-12-09 journal: nan DOI: 10.1101/2020.11.26.20238014 sha: 2aed363d02c8012229075866ccb824358a56afe2 doc_id: 868038 cord_uid: yviywu2f Background: Preliminary data suggests that favipiravir (FVP) might have a role in COVID-19 treatment. Methods: A single-center, prospective, observational, sequential cohort study was performed among consecutive adults hospitalized with PCR-confirmed COVID-19 between March-July,2020. Patients were screened for inclusion by a priori criteria, and were included in the favipiravir cohort if standard-of-care (SOC)+FVP, or the non-favipiravir group if SOC+other antiviral medications without FVP were administered for >48 hours. Treatment allocation was done per national guidelines. For COVID-19 diagnosis and severity, ECDC and WHO definitions were utilized, and daily per protocol hospital follow-up was done. Primary composite end-point was disease progression (14-day all-cause death, need for mechanical ventilation, or immunomodulatory therapy). For statistical comparison, Fisher's exact test and Mann-Whitney U-test were used. Results: In all, 75 patients were included per cohort. In the FVP cohort, chronic heart disease (36/75, 48.0% vs. 16/75, 21.3%, p<0.01) and diabetes mellitus (23/75, 30.7% vs. 10/75, 13.3%, p<0.01) were more prevalent, hospital LOS (18.5+/-15.5 days vs. 13.0+/-8.5 days, p<0.01) was higher. Disease progression (17/75, 22.7% vs. 10/75, 13.3%, p=0.13), 14-day all-cause death (9/75, 12.0% vs. 10/75, 13.3%, p=0.8) and need for mechanical ventillation (8/75, 10.7% vs. 4/75, 5.3%, p=0.22) were similar between groups. Immunomodulatory therapies were administered frequently among patients receiving FVP (10/75, 13.3% vs. 1/75, 1.3%, p<0.01). Conclusions: In this study, favipiravir did not seem to affect disease progression. Further data are needed to position this drug among the anti-SARS-CoV-2 armamentarium. As the pandemic caused by severe acute respiratory syndrome coronavirus-2 (SARS- 71 CoV-2) is ongoing, investigators are searching for therapeutic strategies to cure coronavirus 72 disease-19 (COVID-19). As of September 2020, the number antiviral drugs proven to 73 effectively inhibit viral replication is low [1] . Furthermore, it is not known which antivirals is the author/funder, who has granted medRxiv a license to display the preprint in (which was not certified by peer review) preprint The copyright holder for this this version posted December 9, 2020. is the author/funder, who has granted medRxiv a license to display the preprint in (which was not certified by peer review) preprint The copyright holder for this this version posted December 9, 2020. The primary endpoint was disease progression, a negative composite of any of the 172 following: 1) 14-day all-cause death, 2) need for mechanical ventilation, 3) need for 173 immunomodulatory therapy for COVID-19 at ward or ICU. 14-day all-cause death was is the author/funder, who has granted medRxiv a license to display the preprint in (which was not certified by peer review) preprint The copyright holder for this this version posted December 9, 2020. is the author/funder, who has granted medRxiv a license to display the preprint in (which was not certified by peer review) preprint The copyright holder for this this version posted December 9, 2020. 240 We performed a single-center, prospective observational, sequential cohort study by is the author/funder, who has granted medRxiv a license to display the preprint in (which was not certified by peer review) preprint The copyright holder for this this version posted December 9, 2020. ; https://doi.org/10.1101/2020.11.26.20238014 doi: medRxiv preprint teratogenicity and QTc prolongation. Establishment of long-term safety profile among 261 COVID-19 patients needs more pharmacovigilance data [13] . is the author/funder, who has granted medRxiv a license to display the preprint in (which was not certified by peer review) preprint The copyright holder for this this version posted December 9, 2020. ; https://doi.org/10.1101/2020.11.26.20238014 doi: medRxiv preprint larger numbers, and this might have confounded some baseline characteristics due to the 294 sequential cohort design. The number of included patients is relatively low, however, an exact 295 a priori study size calculation was not feasible due to study design and enrollment. Chest CT 296 was not readily obtainable from some patients due to technical reasons. is the author/funder, who has granted medRxiv a license to display the preprint in (which was not certified by peer review) preprint The copyright holder for this this version posted December 9, 2020. ; https://doi.org/10.1101/2020.11.26.20238014 doi: medRxiv preprint is the author/funder, who has granted medRxiv a license to display the preprint in (which was not certified by peer review) preprint The copyright holder for this this version posted December 9, 2020. is the author/funder, who has granted medRxiv a license to display the preprint in (which was not certified by peer review) preprint The copyright holder for this this version posted December 9, 2020. Table 3 . Independent predictors of disease progression among adult COVID-19 patients 320 included in the study, grouped by progression occurence 321 . CC-BY-NC-ND 4.0 International license It is made available under a perpetuity. is the author/funder, who has granted medRxiv a license to display the preprint in (which was not certified by peer review) preprint The copyright holder for this this version posted December 9, 2020. ; https://doi.org/10.1101/2020.11.26.20238014 doi: medRxiv preprint preparation and review of the manuscript. is the author/funder, who has granted medRxiv a license to display the preprint in (which was not certified by peer review) preprint The copyright holder for this this version posted December 9, 2020. ; https://doi.org/10.1101/2020.11.26.20238014 doi: medRxiv preprint Favipiravir in Critically Ill Patients With COVID-19. Clin Transl Sci 2020;13:880-5. is the author/funder, who has granted medRxiv a license to display the preprint in (which was not certified by peer review) preprint The copyright holder for this this version posted December 9, 2020. ; https://doi.org/10.1101/2020.11.26.20238014 doi: medRxiv preprint National Institutes of Health. COVID-19 Treatment Guidelines Favipiravir strikes 367 the SARS-CoV-2 at its Achilles heel, the RNA polymerase Favipiravir, an antiviral for COVID-19? European Centre for Disease Prevention and Control. Case definition for coronavirus 371 disease 2019 (COVID-19), as of 29 World Health Organization. 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