The administration of interferon-beta1b and favipiravir in patients with COVID-19 pneumonia

Document Type : Original Article

Authors

1 Department of Infectious Diseases, Amir Alam Hospital, Tehran University of Medical Sciences, Tehran,Iran

2 Department of Internal Medicine, Amir Alam Hospital, Tehran University Of Medical Sciences, Tehran, Iran

3 Department of Internal Medicine, Amir Alam Hospital, Tehran University of Medical Sciences, Tehran, Iran

Abstract

Purpose: To assess the efficacy of interferon-beta1b (INF-beta1b) in combination with favipiravir in early treatment of patients with COVD-19 pneumonia.
Methods: This prospective non-controlled study was performed on admitted patients with moderate to severe COVID-19 disease to Amir-Alam hospital. The diagnosis of COVID-19 pneumonia was based on positive RT-PCR test from nasopharyngeal samples and typical spiral chest CT scan findings. At the time of this study, there was the shortage of efficient anti-COVID drugs especially “Remdesivir” due to sanction of Iran.
All the patients received subcutaneous IFN-beta1b plus favipiravir. The patients with severe infection received intravenous dexamethasone. Those who underwent invasive or noninvasive mechanical ventilation, at the admission onset, were excluded from the study.
Results: One hundred and eighty-two patients with moderate to severe COVID-19 pneumonia were included in this study. Among182 patients, 90 cases had moderate and 92 had severe pneumonia. Twenty-one cases with severe pneumonia and 14 cases with moderate pneumonia were transferred to ICU to receive invasive or non-invasive mechanical ventilation. The mean duration of hospital ward admission and ICU stay was 10.69±7.54 and 5.45±2.72 days, respectively. One hundred and seventy-four patients (80.7 %) recovered completely and discharged without need to ICU admission. The response rate was the same in patients with moderate and severe pneumonia. Nine cases (4.9 %) were passed away. Diabetic patients had higher mortality rates.
Conclusion: This study showed the efficacy of IFN-beta1b plus favipiravir in early treatment of patients with moderate to severe COVID-19 pneumonia who did not need to mechanical ventilation.

Keywords

References

1. Wu Z, McGoogan JM. Characteristics of and Important Lessons From the Coronavirus Disease 2019 (COVID-19) Outbreak in China: Summary of a Report of 72 314 Cases From the Chinese Center for Disease Control and Prevention. JAMA. 2020 Apr 7;323(13):1239-1242. doi: 10.1001/jama.2020.2648. PMID: 32091533.
2. Epidemiology Working Group for NCIP Epidemic Response, Chinese Center for Disease Control and Prevention. [The epidemiological characteristics of an outbreak of 2019 novel coronavirus diseases (COVID-19) in China]. Zhonghua Liu Xing Bing Xue Za Zhi. 2020 Feb 10;41(2):145-151. Chinese. doi: 10.3760/cma.j.issn.0254-6450.2020.02.003. PMID: 32064853.
3. World Health Organization. Report of the WHO–China joint mission on coronavirus disease 2019 (COVID-19). https://www.who.int/docs/default-source/coronaviruse/who-china-joint-mission-on-covid-19-final-report.pdf. Accessed Feb 2020.
4. Adams ML, Katz DL, Grandpre J. Population-Based Estimates of Chronic Conditions Affecting Risk for Complications from Coronavirus Disease, United States. Emerg Infect Dis. 2020 Aug;26(8):1831-1833. doi: 10.3201/eid2608.200679. Epub 2020 Apr 23. PMID: 32324118; PMCID: PMC7392427.
5. Smith B, Carson S, Fu R, McDonagh M, Dana T, Chan BKS, et al. Drug Class Review: Disease-modifying Drugs for Multiple Sclerosis: Final Update 1 Report [Internet]. Portland (OR): Oregon Health & Science University; 2010 Aug. PMID: 21348046.
6. Vijay R, Perlman S. Middle East respiratory syndrome and severe acute respiratory syndrome. Curr Opin Virol. 2016 Feb; 16:70-76.
https://doi: 10.1016/j.coviro.2016.01.011.
7. Davoudi-Monfared E, Rahmani H, Khalili H, Hajiabdolbaghi M, Salehi M, Abbasian L, Kazemzadeh H, et al. A Randomized Clinical Trial of the Efficacy and Safety of Interferon β-1a in Treatment of Severe COVID-19. Antimicrob Agents Chemother. 2020 Aug 20;64(9):e01061-20. doi: 10.1128/AAC.01061-20. PMID: 32661006; PMCID: PMC7449227.
8. Dastan F, Nadji SA, Saffaei A, Marjani M, Moniri A, Jamaati H, et al. Subcutaneous administration of interferon beta-1a for COVID-19: A non-controlled prospective trial. Int Immunopharmacol. 2020 Aug;85:106688. doi: 10.1016/j.intimp.2020.106688. Epub 2020 Jun 7. PMID: 32544867; PMCID: PMC7275997.
9. Ivan Fan-Ngai Hung, Kwok-Cheung Lung, Eugene Yuk-Keung Tso, Raymond Liu, Tom Wai-Hin Chung, Man-Yee Chu, and et al. Triple combination of interferon beta-1b, lopinavir-ritonavir, and ribavirin in the treatment of patients admitted to hospital with COVID-19: an open-label, randomized, phase 2 trial. Lancet 2020 May 30(10238) 395:1695–1704. https://doi.org/10.1016/ S0140-6736(20)31042-4.
10. Beigel JH, Tomashek KM, Dodd LE, Mehta AK, Zingman BS, Kalil AC, et al. Remdesivir for the Treatment of Covid-19 - Final Report. N Engl J Med. 2020 Nov 5;383(19):1813-1826. doi: 10.1056/NEJMoa2007764. Epub 2020 Oct 8. PMID: 32445440; PMCID: PMC7262788.
11. Haagmans BL, Kuiken T, Martina BE, Fouchier RA, Rimmelzwaan GF, van Amerongen G, et al. Pegylated interferon-alpha protects type 1 pneumocytes against SARS coronavirus infection in macaques. Nat Med. 2004 Mar;10(3):290-3. doi: 10.1038/nm1001. Epub 2004 Feb 22. PMID: 14981511; PMCID: PMC7095986.
12. Kindler E, Thiel V, Weber F. Interaction of SARS and MERS Coronaviruses with the Antiviral Interferon Response. Adv Virus Res. 2016;96:219-243. doi: 10.1016/bs.aivir.2016.08.006. Epub 2016 Sep 9. PMID: 27712625; PMCID: PMC7112302.
13. Morgenstern B, Michaelis M, Baer PC, Doerr HW, Cinatl J Jr. Ribavirin and interferon-beta synergistically inhibit SARS-associated coronavirus replication in animal and human cell lines. Biochem Biophys Res Commun. 2005 Jan 28;326(4):905-8. doi: 10.1016/j.bbrc.2004.11.128. PMID: 15607755; PMCID: PMC7092851.
14. Cinatl J, Morgenstern B, Bauer G, Chandra P, Rabenau H, Doerr HW. Treatment of SARS with human interferons. Lancet. 2003 Jul 26;362(9380):293-4. doi: 10.1016/s0140-6736(03)13973-6. Erratum in: Lancet. 2003 Aug 30;362(9385):748. PMID: 12892961; PMCID: PMC7112413.
15. Bosi C, Gori A, Raviglione M. Interferon beta in COVID-19: a landmark looming in the uncharted sea of COVID-19? J Public Health Emerg. 2020 June 4: 8 doi: 10.21037/jphe.2020.03.08
16. Blanco-Melo D, Nilsson-Payant BE, Liu WC, Uhl S, Hoagland D, Møller R, et al. Imbalanced Host Response to SARS-CoV-2 Drives Development of COVID-19. Cell. 2020 May 28;181(5):1036-1045.e9. doi: 10.1016/j.cell.2020.04.026. Epub 2020 May 15. PMID: 32416070; PMCID: PMC7227586.
17. Laver T, Nozell SE, Benveniste EN. IFN-beta-mediated inhibition of IL-8 expression requires the ISGF3 components Stat1, Stat2, and IRF-9. J Interferon Cytokine Res. 2008 Jan;28(1):13-23. doi: 10.1089/jir.2007.0062. PMID: 18370868.
18. Kiss J, Yegutkin GG, Koskinen K, Savunen T, Jalkanen S, Salmi M. IFN-beta protects from vascular leakage via up-regulation of CD73. Eur J Immunol. 2007 Dec;37(12):3334-8. doi: 10.1002/eji.200737793. PMID: 18034430.
19. Bellingan G, Maksimow M, Howell DC, Stotz M, Beale R, Beatty M, et al. The effect of intravenous interferon-beta-1a (FP-1201) on lung CD73 expression and on acute respiratory distress syndrome mortality: an open-label study. Lancet Respir Med. 2014 Feb;2(2):98-107. doi: 10.1016/S2213-2600(13)70259-5. Epub 2013 Dec 23. PMID: 24503265.
20. Cai Q, Yang M, Liu D, Chen J, Shu D, Xia J, et al. Experimental Treatment with Favipiravir for COVID-19: An Open-Label Control Study. Engineering (Beijing). 2020 Oct;6(10):1192-1198. doi: 10.1016/j.eng.2020.03.007. Epub 2020 Mar 18. PMID: 32346491; PMCID: PMC7185795.
21. James Ives M. Preliminary report of favipiravir observational study in Japan released. 2020 May: Fujita Health University. https://www.news-medical.net/news/20200602/Preliminary-report-of-Favipiravir-Observational-Study-in-Japan-released.aspx [Internet].
22. RECOVERY Collaborative Group, Horby P, Lim WS, Emberson JR, Mafham M, Bell JL, et al. Dexamethasone in Hospitalized Patients with Covid-19. N Engl J Med. 2021 Feb 25;384(8):693-704. doi: 10.1056/NEJMoa2021436. Epub 2020 Jul 17. PMID: 32678530; PMCID: PMC7383595.
23. Huang C, Wang Y, Li X, Ren L, Zhao J, Hu Y, and et al. Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. Lancet. 2020 Feb 15;395(10223):497-506. doi: 10.1016/S0140-6736(20)30183-5.
24. Wang D, Hu B, Hu C, Zhu F, Liu X, Zhang J, et al. Clinical Characteristics of 138 Hospitalized Patients With 2019 Novel Coronavirus-Infected Pneumonia in Wuhan, China. JAMA. 2020 Mar 17;323(11):1061-1069. doi: 10.1001/jama.2020.1585. Erratum in: JAMA. 2021 Mar 16;325(11):1113. PMID: 32031570; PMCID: PMC7042881.
25. Piroth L, Cottenet J, Mariet A-S, Bonniaud Ph, Blot M, Tubert-bitter P, and et al. Comparison of the characteristics, morbidity, and mortality of COVID-19 and seasonal influenza: a nationwide, population-based retrospective cohort study. Lancet Respir Med. 2021 Mar;9(3):251-259. doi: 10.1016/S2213-2600(20)30527-0.
Trends in Pharmaceutical Sciences
Volume 7, Issue 2
June 2021
Pages 127-134

Files

Share

How to cite

Statistics