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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doi:10.1007/s10096-021-04307-1DOI record:
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"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>",
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