AUTHOR=Babayigit Cenk , Kokturk Nurdan , Kul Seval , Cetinkaya Pelin Duru , Atis Nayci Sibel , Argun Baris Serap , Karcioglu Oguz , Aysert Pinar , Irmak Ilim , Akbas Yuksel Aycan , Sekibag Yonca , Baydar Toprak Oya , Azak Emel , Mulamahmutoglu Sait , Cuhadaroglu Caglar , Demirel Aslihan , Kerget Bugra , Baran Ketencioglu Burcu , Ozger Hasan Selcuk , Ozkan Gulcihan , Ture Zeynep , Ergan Begum , Avkan Oguz Vildan , Kilinc Oguz , Ercelik Merve , Ulukavak Ciftci Tansu , Alici Ozlem , Nurlu Temel Esra , Ataoglu Ozlem , Aydin Asena , Cetiner Bahcetepe Dilek , Gullu Yusuf Taha , Fakili Fusun , Deveci Figen , Kose Neslihan , Tor Muge Meltem , Gunluoglu Gulsah , Altin Sedat , Turgut Teyfik , Tuna Tibel , Ozturk Onder , Dikensoy Oner , Yildiz Gulhan Pinar , Basyigit Ilknur , Boyaci Hasim , Oguzulgen Ipek Kivilcim , Borekci Sermin , Gemicioglu Bilun , Bayraktar Firat , Elbek Osman , Hanta Ismail , Kuzu Okur Hacer , Sagcan Gulseren , Uzun Oguz , Akgun Metin , Altinisik Goksel , Dursun Berna , Cakir Edis Ebru , Gulhan Erkmen , Oner Eyuboglu Fusun , Gultekin Okkes , Havlucu Yavuz , Ozkan Metin , Sakar Coskun Aysin , Sayiner Abdullah , Kalyoncu A. Fuat , Itil Oya , Bayram Hasan TITLE=The association of antiviral drugs with COVID-19 morbidity: The retrospective analysis of a nationwide COVID-19 cohort JOURNAL=Frontiers in Medicine VOLUME=9 YEAR=2022 URL=https://www.frontiersin.org/journals/medicine/articles/10.3389/fmed.2022.894126 DOI=10.3389/fmed.2022.894126 ISSN=2296-858X ABSTRACT=Background and objectives

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.

Methods

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.

Results

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 (n = 328), lopinavir/ritonavir (n = 55), and oseltamivir (n = 761) were administered as antiviral agents, and hydroxychloroquine (HCQ, n = 1,382) and azithromycin (n = 738) were used for their immunomodulatory activity. Lopinavir/ritonavir (β [95% CI]: 4.71 [2.31–7.11]; p = 0.001), favipiravir (β [95% CI]: 3.55 [2.56–4.55]; p = 0.001) and HCQ (β [95% CI]: 0.84 [0.02–1.67]; p = 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]; 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.