Kasyanenko KV, Kozlov KV, Maltsev OV, Lapikov II, Gordienko VV, Sharabhanov VV, Sorokin PV, Zhdanov KV. Evaluation of the effectiveness of riamilovir in the complex therapy of patients with COVID-19. Terapevticheskii Arkhiv (Ter. Arkh). 2021; 93 (3): 290–294. DOI: 10.26442/00403660.2021.03.200719
Оценка эффективности риамиловира в комплексной терапии больных COVID-19
Kasyanenko KV, Kozlov KV, Maltsev OV, Lapikov II, Gordienko VV, Sharabhanov VV, Sorokin PV, Zhdanov KV. Evaluation of the effectiveness of riamilovir in the complex therapy of patients with COVID-19. Terapevticheskii Arkhiv (Ter. Arkh). 2021; 93 (3): 290–294. DOI: 10.26442/00403660.2021.03.200719
Цель. Оценить влияние противовирусной терапии Риамиловиром на скорость элиминации SARS-CoV-2 и длительность госпитализации среднетяжелых пациентов с COVID-19. Материалы и методы. В исследование включены 69 пациентов с лабораторно подтвержденной COVID-19-инфекцией средней степени тяжести. Опытную группу составили 34 пациента, которые получали Риамиловир в режиме off-label в дозировке 1250 мг/сут в течение 5 дней (по схеме 250 мг 5 раз в день), группа сравнения – 35 пациентов, получавших комбинацию рибавирина и умифеновира в режиме 800 мг/сут для каждого препарата на протяжении 5 дней. Противовирусная терапия назначалась в первые 72 ч от момента появления клинических симптомов заболевания. Конечными точками анализа стали санация от вируса SARS-CoV-2 по результатам исследования методом полимеразной цепной реакции (ПЦР) отделяемого со слизистой оболочки носоглотки и ротоглотки к 7-м суткам госпитализации и выписка пациента к 14-м суткам госпитализации. Результаты. Клиническое улучшение у пациентов, получавших противовирусную терапию Риамиловиром, наступало статистически значимо быстрее, чем в группе сравнения, кроме того, по результатам ПЦР на фоне лечения Риамиловиром отмечалась достоверно более быстрая элиминация вируса из верхних дыхательных путей. Заключение. Раннее назначение Риамиловира по сравнению с комбинацией умифеновира и рибавирина для лечения среднетяжелых пациентов с инфекцией, вызванной SARS-CoV-2, статистически значимо повышало вероятность клинического улучшения к 14-му дню госпитализации наряду с увеличением вероятности получения первого отрицательного результата ПЦР на РНК SARS-CoV-2 к 7-м суткам пребывания в стационаре.
Aim. In this study we evaluated the effects of riamilovir on SARS-CoV-2 viral shedding and on admission duration in patients with moderate COVID-19. Materials and methods. We have used data from 69 health records of patients with moderate severe PCR confirmed SARS-CoV-2 infection. Control group included 34 patients treated with off-label riamilovir 1250 mg per day for 5 days (250 mg 5 times a day), comparison groups – 35 patients, who received ribavirin and umifenovir 800 mg a day for 5 days. The antiviral therapy was administered within 72 hours from the onset of the disease. The primary endpoints were elimination of virus in oropharyngeal and nasopharyngeal swabs on 7 day of admission and discharge from the hospital by 14 day. Results. Patients assigned to riamilovir had significantly shorter time to clinical improvement as well as increased PCR negative rate by day 7. Conclusion. Yearly administration of riamilovir as opposed to the umifenovir and ribavirin in therapy of moderate SARS-CoV-2 infection was associated with significant shorter time to clinical improvement by 14 day of hospitalization. PCR negative rate by 7 days of hospitalization is significantly more likely in riamilovir group.
1. COVID-19 Coronavirus pandemic. Reported Cases and Deaths by Country, Territory, or Conveyance. Accessed: February 10, 2021. https://www.worldometers.info/coronavirus/Coronavirus disease (COVID-19). Situation Report – 132.
2. Zhu N, Zhang D, Wang W, et al. A novel coronavirus from patient with pneumonia in China. New Engl J Med. 2020;382:727-33. doi: 10.1056/NEJMoa2001017
3. Zumla A, Chan JFW, Azhar EI, et al. Coronaviruses – drug discovery and therapeutic options. Natural reviews. Drug Discovery. 2016;15(5):327-47. doi: 10.1038/nrd.2015.37
4. Dustin LB, Bartolini B, Capobianchi MR, Pistello M. Hepatitis C virus: life cycle in cells, infection and host response, and analysis of molecular markers influencing the outcome of infection and response to therapy. Clin Microbiol Infect. 2016;22(10):826-32. doi: 10.1016/j.cmi.2016.08.025
5. Te Velthuis AJW. Common and unique features of viral RNA-dependent polymerases. Cell Mol Life Sci. 2014;71(22):4403-20.
doi: 10.1007/s00018-014-1695-z
6. McKenna CE, Levy JN, Khawli LA, et al. Inhibitors of viral nucleic acid polymerases. Pyrophosphate analogues. American Chemical Society. Symposium Series. 1986;401:1-16.
doi: 10.1021/bk-1989-0401.ch001
7. De Clercq E, Li G. Approved antiviral drugs over the past 50 years. Clin Microbiol Rev. 2016;29(3):695-747. doi: 10.1128/CMR.00102-15
8. Ju J, Li X, Kumar S, et al. Nucleotide analogues as inhibitors of SARS-CoV polymerase. Pharmacol Res Perspectives. 2020;8(6):1-9. doi: 10.1101/2020.03.12.989186
9. Subissi L, Posthuma CC, Collete A, et al. One severe acute respiratory syndrome coronavirus protein complex integrates processive RNA polymerase and exonuclease activities. PNAS. 2014;111(37):3900-09. doi: 10.1073/pnas.1323705111
10. Cai Q, Yang M, Liu D, et al. Experimental Treatment with Favipiravir for COVID-19: An Open-Label Control Study Engineering (Beijing). 2020 Mar 18. doi: 10.1016/j.eng.2020.03.007
11. Крюков Е.В., Чернецов В.А., Паценко М.Б., и др. Алгоритмы ведения пациентов с новой коронавирусной инфекцией COVID-19 в стационаре: методические рекомендации. Consilium Medicum. 2020;22(11) [Kryukov EV, Chernetsov VA, Patsenko MB, et al. Algorithms for the management of patients with a new coronavirus COVID-19 infection in a hospital. Guidelines. Consilium Medicum. 2020;22(11) (In Russ.)]. doi: 10.26442/20751753.2020.11.200520
12. Chen C, Zhang Y, Huang J, et al. Favipiravir versus Arbidol for COVID-19: a randomized clinical trial. medRxiv. 2020.03.17.20037432. doi: 10.1101/2020.03.17.20037432
13. Касьяненко К.В., Мальцев О.В., Козлов К.В., и др. Клиническая эффективность и безопасность применения Риамиловира при лечении пациентов с инфекцией, вызванной SARS-CoV-2. Антибиотики и химиотерапия. 2020;65:11-2 [Kasianenko KV, Maltsev OV, Kozlov KV, et al. Clinical efficiency and safety of Riamilovir for treating patients with SARS-CoV-2. Antibiotics and Chemotherapy. 2020;65:11-2 (In Russ.)]. doi: 0.37489/0235-2990-2020-65-11-12-16-21
14. Временные методические рекомендации по профилактике, диагностике и лечению новой коронавирусной инфекции (COVID-19) Министерства здравоохранения Российской Федерации. Режим доступа: http://static-0.minzdrav.gov.ru/system/attachments/attaches/000/051/777/original/030902020_COVID-19_.... Ссылка активна на 11.02.2021[Temporary guidelines for the prevention, diagnosis and treatment of new coronavirus infection (COVID-19) of the Ministry of Health of the Russian Federation. Available at: http://static-0.minzdrav.gov.ru/system/attachments/attaches/000/051/777/original/030902020_COVID-19_... . Accessed: 11.02.2021 (In Russ.)].
15. Лиознов Д.А., Токин И.И., Зубкова Т.Г., Сорокин П.В. Практика применения отечественного противовирусного препарата в этиотропной терапии острой респираторной вирусной инфекции. Терапевтический архив. 2020;92(12):59-63 [Lioznov DA, Tokin II, Zubkova TG, Sorokin PV. The practice of using a domestic antiviral drug in the etiotropic therapy of acute respiratory viral infection. Terapevticheskii Arkhiv (Ter. Arkh). 2020;92(12):59-63 (In Russ.)]. doi: 10.26442/00403660.2020.12.200427
16. Wu X, Yu K, Wang Y, et al. Efficacy and safety of triazavirin therapy for coronavirus disease 2019: a pilot randomized controlled trial. Engineering (Beijing, China), 2020 Sep 8. doi: 10.1016/j.eng.2020.08.011
17. Huang C, Wang Y, Li X, et al. Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. Lancet. 2020;396:497-506.
18. Chan K, Lai S, Chu C, et al. Treatment of severe acute respiratory syndrome with lopinavir/ritonavir: a multicenter retrospective matched cohort study. Hong Kong Med J. 2003;9:399-406.
________________________________________________
1. COVID-19 Coronavirus pandemic. Reported Cases and Deaths by Country, Territory, or Conveyance. Accessed: February 10, 2021. https://www.worldometers.info/coronavirus/Coronavirus disease (COVID-19). Situation Report – 132.
2. Zhu N, Zhang D, Wang W, et al. A novel coronavirus from patient with pneumonia in China. New Engl J Med. 2020;382:727-33. doi: 10.1056/NEJMoa2001017
3. Zumla A, Chan JFW, Azhar EI, et al. Coronaviruses – drug discovery and therapeutic options. Natural reviews. Drug Discovery. 2016;15(5):327-47. doi: 10.1038/nrd.2015.37
4. Dustin LB, Bartolini B, Capobianchi MR, Pistello M. Hepatitis C virus: life cycle in cells, infection and host response, and analysis of molecular markers influencing the outcome of infection and response to therapy. Clin Microbiol Infect. 2016;22(10):826-32. doi: 10.1016/j.cmi.2016.08.025
5. Te Velthuis AJW. Common and unique features of viral RNA-dependent polymerases. Cell Mol Life Sci. 2014;71(22):4403-20.
doi: 10.1007/s00018-014-1695-z
6. McKenna CE, Levy JN, Khawli LA, et al. Inhibitors of viral nucleic acid polymerases. Pyrophosphate analogues. American Chemical Society. Symposium Series. 1986;401:1-16. doi: 10.1021/bk-1989-0401.ch001
7. De Clercq E, Li G. Approved antiviral drugs over the past 50 years. Clin Microbiol Rev. 2016;29(3):695-747. doi: 10.1128/CMR.00102-15
8. Ju J, Li X, Kumar S, et al. Nucleotide analogues as inhibitors of SARS-CoV polymerase. Pharmacol Res Perspectives. 2020;8(6):1-9. doi: 10.1101/2020.03.12.989186
9. Subissi L, Posthuma CC, Collete A, et al. One severe acute respiratory syndrome coronavirus protein complex integrates processive RNA polymerase and exonuclease activities. PNAS. 2014;111(37):3900-09. doi: 10.1073/pnas.1323705111
10. Cai Q, Yang M, Liu D, et al. Experimental Treatment with Favipiravir for COVID-19: An Open-Label Control Study Engineering (Beijing). 2020 Mar 18. doi: 10.1016/j.eng.2020.03.007
11. Kryukov EV, Chernetsov VA, Patsenko MB, et al. Algorithms for the management of patients with a new coronavirus COVID-19 infection in a hospital. Guidelines. Consilium Medicum. 2020;22(11) (In Russ.) doi: 10.26442/20751753.2020.11.200520
12. Chen C, Zhang Y, Huang J, et al. Favipiravir versus Arbidol for COVID-19: a randomized clinical trial. medRxiv. 2020.03.17.20037432. doi: 10.1101/2020.03.17.20037432
13. Kasianenko KV, Maltsev OV, Kozlov KV, et al. Clinical efficiency and safety of Riamilovir for treating patients with SARS-CoV-2. Antibiotics and Chemotherapy. 2020;65:11-2 (In Russ.) doi: 0.37489/0235-2990-2020-65-11-12-16-21
14. Temporary guidelines for the prevention, diagnosis and treatment of new coronavirus infection (COVID-19) of the Ministry of Health of the Russian Federation. Available at: http://static-0.minzdrav.gov.ru/system/attachments/attaches/000/051/777/original/030902020_COVID-19_... . Accessed: 11.02.2021 (In Russ.)
15. Lioznov DA, Tokin II, Zubkova TG, Sorokin PV. The practice of using a domestic antiviral drug in the etiotropic therapy of acute respiratory viral infection. Terapevticheskii Arkhiv (Ter. Arkh). 2020;92(12):59-63 (In Russ.)].
doi: 10.26442/00403660.2020.12.200427
16. Wu X, Yu K, Wang Y, et al. Efficacy and safety of triazavirin therapy for coronavirus disease 2019: a pilot randomized controlled trial. Engineering (Beijing, China), 2020 Sep 8. doi: 10.1016/j.eng.2020.08.011
17. Huang C, Wang Y, Li X, et al. Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. Lancet. 2020;396:497-506.
18. Chan K, Lai S, Chu C, et al. Treatment of severe acute respiratory syndrome with lopinavir/ritonavir: a multicenter retrospective matched cohort study. Hong Kong Med J. 2003;9:399-406.
1 ФГБВОУ ВО «Военно-медицинская академия им. С.М. Кирова» Минобороны России, Санкт-Петербург, Россия;
2 ФГАОУ ВО «Балтийский федеральный университет им. Иммануила Канта», Калининград, Россия;
3 ООО «Азол фарма», Новоуральск, Россия
*dr.snegur@gmail.com
________________________________________________
Kristina V. Kasyanenko*1, Konstantin V. Kozlov1, Oleg V. Maltsev1, Igor I. Lapikov2, Vera V. Gordienko1, Valerian V. Sharabhanov1, Pavel V. Sorokin3, Konstantin V. Zhdanov1
1 Kirov Military Medical Academy, Saint Petersburg, Russia;
2 Immanuel Kant Baltic Federal University, Kaliningrad, Russia;
3 LLC “Azol Farma”, Novouralsk, Russia
*dr.snegur@gmail.com