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. 2022 Aug 31:9:894126.
doi: 10.3389/fmed.2022.894126. eCollection 2022.

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

Cenk Babayigit  1 , Nurdan Kokturk  2 , Seval Kul  3 , Pelin Duru Cetinkaya  4   5 , Sibel Atis Nayci  6 , Serap Argun Baris  7 , Oguz Karcioglu  8 , Pinar Aysert  9 , Ilim Irmak  10 , Aycan Akbas Yuksel  11 , Yonca Sekibag  12 , Oya Baydar Toprak  5 , Emel Azak  13 , Sait Mulamahmutoglu  12 , Caglar Cuhadaroglu  14 , Aslihan Demirel  15 , Bugra Kerget  16 , Burcu Baran Ketencioglu  17 , Hasan Selcuk Ozger  9 , Gulcihan Ozkan  18   19 , Zeynep Ture  20 , Begum Ergan  21 , Vildan Avkan Oguz  22 , Oguz Kilinc  21 , Merve Ercelik  23 , Tansu Ulukavak Ciftci  2 , Ozlem Alici  24 , Esra Nurlu Temel  25 , Ozlem Ataoglu  23 , Asena Aydin  26 , Dilek Cetiner Bahcetepe  26 , Yusuf Taha Gullu  27 , Fusun Fakili  28 , Figen Deveci  29 , Neslihan Kose  30 , Muge Meltem Tor  31 , Gulsah Gunluoglu  32 , Sedat Altin  32 , Teyfik Turgut  29 , Tibel Tuna  27 , Onder Ozturk  33 , Oner Dikensoy  34 , Pinar Yildiz Gulhan  23 , Ilknur Basyigit  7 , Hasim Boyaci  7 , Ipek Kivilcim Oguzulgen  2 , Sermin Borekci  12 , Bilun Gemicioglu  12 , Firat Bayraktar  35 , Osman Elbek  36 , Ismail Hanta  5 , Hacer Kuzu Okur  14 , Gulseren Sagcan  14 , Oguz Uzun  27 , Metin Akgun  16 , Goksel Altinisik  37 , Berna Dursun  38 , Ebru Cakir Edis  39 , Erkmen Gulhan  40 , Fusun Oner Eyuboglu  41 , Okkes Gultekin  42 , Yavuz Havlucu  42 , Metin Ozkan  38 , Aysin Sakar Coskun  42 , Abdullah Sayiner  43 , A Fuat Kalyoncu  10 , Oya Itil  21 , Hasan Bayram  44   45
Affiliations

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

Cenk Babayigit et al. Front Med (Lausanne). .

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.

Keywords: COVID-19 morbidity; ICU requirement; antiviral agents; invasive mechanical ventilation; length of hospitalization.

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Conflict of interest statement

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.

Figures

FIGURE 1
FIGURE 1
The timeline for the treatment protocols applied by the guidelines by the Scientific Board of the Ministry of Health (SBMH) of Turkey.
FIGURE 2
FIGURE 2
The enrollment of the study population.
FIGURE 3
FIGURE 3
Frequency of the patients, who were administered any of the given drugs; either alone or in combination with other drugs.
See this image and copyright information in PMC

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