medsovetМедицинский СоветMeditsinskiy sovet = Medical Council2079-701X2658-5790REMEDIUM GROUP Ltd.10.21518/2079-701X-2022-16-23-304-309medsovet-7310Research ArticleCOVID-19Оценка ассоциации полиморфизмов CES1 (rs2244613) с безопасностью применения ремдесивира у госпитализированных пациентов с COVID-19Evaluation of the association of CES1 (rs2244613) polymorphisms with the safety of remdesivir in hospitalized patients with COVID-19https://orcid.org/0000-0002-1242-0833ТемирбулатовИ. И.TemirbulatovI. I.

Темирбулатов Ильяс Ильдарович - аспирант кафедры клинической фармакологии и терапии имени Б.Е. Вотчала, РМАНПО; врач – клинический фармаколог, ГКБ №15 имени О.М. Филатова.

125993, Москва, ул. Баррикадная, д. 2/1, стр. 1; 111539, Москва, ул. Вешняковская, д. 23

Ilyas I. Temirbulatov - Postgraduate Student of the Department of Clinical Pharmacology and Therapy named after Academician B.E. Votchal, Russian Medical Academy of Continuous Professional Education; Clinical Pharmacologist, City Clinical Hospital No. 15 named after О.М. Filatov.

2/1, Bldg. 1, Barrikadnaya St., Moscow, 125993; 23, Veshnyakovskaya St., Moscow, 111539

temirbulatov.ilyas@gmail.comhttps://orcid.org/0000-0001-7903-2977КрюковА. В.KryukovA. V.

Крюков Александр Валерьевич – кандидат медицинских наук, доцент кафедры клинической фармакологии и терапии имени Б.Е. Вотчала, РМАНПО; заведующий отделением клинической фармакологии, врач – клинический фармаколог, ГКБ №15 имени О.М. Филатова.

125993, Москва, ул. Баррикадная, д. 2/1, стр. 1; 111539, Москва, ул. Вешняковская, д. 23

Alexander V. Kryukov - Cand. Sci. (Med.), Associate Professor of the Department of Clinical Pharmacology and Therapy named after Academician B.E. Votchal, Russian Medical Academy of Continuous Professional Education; Clinical Pharmacologist, Head of the Department of Clinical Pharmacology, City Clinical Hospital No. 15 named after О.М. Filatov.

2/1, Bldg. 1, Barrikadnaya St., Moscow, 125993; 23, Veshnyakovskaya St., Moscow, 111539

alex.kryukov90@yandex.ruhttps://orcid.org/0000-0002-9307-4994МирзаевК. Б.MirzaevK. B.

Мирзаев Карин Бадавиевич - доктор медицинских наук, проректор по научной работе и инновациям, директор Научно-исследовательского института молекулярной и персонализированной медицины.

125993, Москва, ул. Баррикадная, д. 2/1, стр. 1

Karin B. Mirzaev - Dr. Sci. (Med.), Vice-Rector for Research and Innovation, Director of the Research Institute of Molecular and Personalized Medicine, Russian Medical Academy of Continuous Professional Education.

2/1, Bldg. 1, Barrikadnaya St., Moscow, 125993

karin05doc@yandex.ruhttps://orcid.org/0000-0003-3278-5941ДенисенкоН. П.DenisenkoN. P.

Денисенко Наталья Павловна - кандидат медицинских наук, заместитель директора Научно-исследовательского института молекулярной и персонализированной медицины, доцент кафедры клинической фармакологии и терапии имени академика Б.Е. Вотчала.

125993, Москва, ул. Баррикадная, д. 2/1, стр. 1

Natalia P. Denisenko - Cand. Sci. (Med.), Deputy Director of the Research Institute of Molecular and Personalized Medicine, Associate Professor of the Department of Clinical Pharmacology and Therapy named after Academician B.E. Votchal, Russian Medical Academy of Continuous Professional Education.

2/1, Bldg. 1, Barrikadnaya St., Moscow, 125993

natalypilipenko3990@gmail.comhttps://orcid.org/0000-0001-9001-1499АбдуллаевШ. П.AbdullaevSh. P.

Абдуллаев Шерзод Пардабоевич – кандидат биологических наук, заведующий отделом предиктивных и прогностических биомаркеров Научно-исследовательского института молекулярной и персонализированной медицины.

125993, Москва, ул. Баррикадная, д. 2/1, стр. 1

Sherzod P. Abdullaev - Cand. Sci. (Bio.), Head of the Department of Predictive and Prognostic Biomarkers of the Research Institute of Molecular and Personalized Medicine, Russian Medical Academy of Continuous Professional Education.

2/1, Bldg. 1, Barrikadnaya St., Moscow, 125993

sherzodx5@gmail.comhttps://orcid.org/0000-0003-3194-4410КачановаА. А.KachanovaA. A.

Качанова Анастасия Алексеевна - младший научный сотрудник Научно-исследовательского института молекулярной и персонализированной медицины.

125993, Москва, ул. Баррикадная, д. 2/1, стр. 1

Anastasia A. Kachanova - Junior Researcher, Research Institute of Molecular and Personalized Medicine, Russian Medical Academy of Continuous Professional Education.

2/1, Bldg. 1, Barrikadnaya St., Moscow, 125993

aakachanova@yandex.ruhttps://orcid.org/0000-0001-5166-7903СозаеваЖ. А.SozaevaZh. A.

Созаева Жаннет Алимовна - младший научный сотрудник Научно-исследовательского института молекулярной и персонализированной медицины.

125993, Москва, ул. Баррикадная, д. 2/1, стр. 1

Zhannet A. Sozaeva - Junior Researcher, Research Institute of Molecular and Personalized Medicine, Russian Medical Academy of Continuous Professional Education.

2/1, Bldg. 1, Barrikadnaya St., Moscow, 125993

zhannet.sozaeva@yandex.ruhttps://orcid.org/0000-0003-4192-654XЖиряковаА. С.ZhiryakovaA. S.

Жирякова Анна Сергеевна - аспирант кафедры клинической фармакологии и терапии имени Б.Е. Вотчала.

125993, Москва, ул. Баррикадная, д. 2/1, стр. 1

Anna S. Zhiryakova - Postgraduate Student of the Department of Clinical Pharmacology and Therapy named after Academican B.E. Votchal, Russian Medical Academy of Continuous Professional Education.

2/1, Bldg. 1, Barrikadnaya St., Moscow, 125993

mya1017@yandex.ruhttps://orcid.org/0000-0003-2289-1900ШевчукЮ. В.ShevchukYu. V.

Шевчук Юлия Викторовна - аспирант кафедры клинической фармакологии и терапии имени Б.Е. Вотчала.

125993, Москва, ул. Баррикадная, д. 2/1, стр. 1

Yuliya V. Shevchuk - Postgraduate Student of the Department of Clinical Pharmacology and Therapy named after Academician B.E. Votchal, Russian Medical Academy of Continuous Professional Education.

2/1, Bldg. 1, Barrikadnaya St., Moscow, 125993

juviktorovna@yandex.ruhttps://orcid.org/0000-0003-3568-5065ВечоркоВ. И.VechorkoV. I.

Вечорко Валерий Иванович - доктор медицинских наук, главный врач.

111539, Москва, ул. Вешняковская, д. 23

Valery I. Vechorko - Dr. Sci. (Med.), Chief Physician, City Clinical Hospital No. 15 named after О.М. Filatov.

23, Veshnyakovskaya St., Moscow, 111539

vvechorko@yandex.ruhttps://orcid.org/0000-0002-3010-755XАверковО. В.AverkovO. V.

Аверков Олег Валерьевич - доктор медицинских наук, профессор, заместитель главного врача, руководитель регионального сосудистого центра.111539, Москва, ул. Вешняковская, д. 23

Oleg V. Averkov - Dr. Sci. (Med.), Deputy Chief Physician, Head of Regional Vascular Center, City Clinical Hospital No. 15 named after О.М. Filatov.

23, Veshnyakovskaya St., Moscow, 111539

oleg.averkov@gmail.comhttps://orcid.org/0000-0002-4496-3680СычевД. А.SychevD. A.

Сычев Дмитрий Алексеевич - академик РАН, доктор медицинских наук, профессор, ректор, заведующий кафедрой клинической фармакологии и терапии имени Б.Е. Вотчала.

125993, Москва, ул. Баррикадная, д. 2/1, стр. 1

Dmitry A. Sychev - Acad. RAS, Dr. Sci. (Med.), Professor, Rector, Head Department of the Clinical Pharmacology and Therapy named after Academician B.E. Votchal, Russian Medical Academy of Continuous Professional Education.

2/1, Bldg. 1, Barrikadnaya St., Moscow, 125993

dimasychev@mail.ruРоссийская медицинская академия непрерывного профессионального образования; Городская клиническая больница №15 имени О.М. ФилатоваРоссияRussian Medical Academy of Continuous Professional Education; City Clinical Hospital No. 15 named after О.М. FilatovRussian FederationРоссийская медицинская академия непрерывного профессионального образованияРоссияRussian Medical Academy of Continuous Professional EducationRussian FederationГородская клиническая больница №15 имени О.М. ФилатоваРоссияCity Clinical Hospital No. 15 named after О.М. FilatovRussian Federation202218012023023304309Copyright © Темирбулатов И.И., Крюков А.В., Мирзаев К.Б., Денисенко Н.П., Абдуллаев Ш.П., Качанова А.А., Созаева Ж.А., Жирякова А.С., Шевчук Ю.В., Вечорко В.И., Аверков О.В., Сычев Д.А., 20232023Темирбулатов И.И., Крюков А.В., Мирзаев К.Б., Денисенко Н.П., Абдуллаев Ш.П., Качанова А.А., Созаева Ж.А., Жирякова А.С., Шевчук Ю.В., Вечорко В.И., Аверков О.В., Сычев Д.А.Temirbulatov I.I., Kryukov A.V., Mirzaev K.B., Denisenko N.P., Abdullaev S.P., Kachanova A.A., Sozaeva Z.A., Zhiryakova A.S., Shevchuk Y.V., Vechorko V.I., Averkov O.V., Sychev D.A.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.med-sovet.pro/jour/article/view/7310Введение

Введение. Вспышка новой инфекции COVID-19 стала настоящим вызовом для всего общества, и в первую очередь для системы здравоохранения. Разработка новых препаратов – сложный и долгий процесс. В начале пандемии это побудило к интенсивному изучению уже известных лекарств для терапии. Ремдесивир первоначально исследовался для лечения вируса Эболы. После начала пандемии COVID-19 была показана его in vitro активность против SARS-CoV-2. Последовавшие затем клинические исследования показали эффективность ремдесивира в сокращении времени до выздоровления.

Цель

Цель. Оценить влияние носительства полиморфных аллелей CES1 (A > C, rs2244613) на профиль безопасности при терапии ремдесивиром.

Материалы и методы

Материалы и методы. В исследование были включены 154 пациента, госпитализированных с коронавирусной инфекцией. Все пациенты получали ремдесивир в качестве этиотропной терапии в стандартном режиме: 200 мг в первые сутки, затем 100 мг раз в сутки в течение 5–10 дней. Во время наблюдения отмечались клинические и лабораторные признаки нежелательных побочных явлений. Каждому пациенту был произведен забор венозной крови для проведения фармакогенетического исследования. Генотипирование проводилось с помощью методики полимеразной цепной реакции в режиме реального времени. Статистический анализ результатов проводился с помощью программы IBM SPSS Statistics 23.0.

Результаты

Результаты. Не было выявлено достоверных ассоциаций носительства различных вариантов CES1 с частотой нежелательных реакций (брадикардии, тошнота, рвота) и лабораторными маркерами нежелательных явлений (уровни АЛТ, АСТ, креатинина).

Выводы

Выводы. В нашем исследовании не было обнаружено ассоциации носительства полиморфизмов гена CES1 с параметрами безопасности ремдесивира у госпитализированных пациентов с COVID-19. Необходимы дальнейшие исследования возможностей персонализации терапии COVID-19 с помощью фармакогенетического тестирования.

Introduction

Introduction. An outbreak of novel COVID-19 infection has become a real challenge for the entire human society, and first of all for the healthcare services. The development of new drugs is a complex and lengthy process. At the beginning of the pandemic, it forced an intensive study of well-known drugs for the therapy. Remdesivir was first investigated as a potential treatment for Ebola virus. After beginning of the COVID-19 pandemic, in vitro evaluations demonstrated its activity against SARS-CoV-2. Subsequent clinical studies showed the efficacy of remdesivir in shortening the time to recovery.

Aim

Aim. To evaluate the effect of the carriage of polymorphic alleles of the CES1 gene (A > C, rs2244613) on the safety profile of remdesivir therapy.

Materials and methods

Materials and methods. A total of 154 patients hospitalized with coronavirus infection were included in the study. All patients received remdesivir as etiotropic therapy in the standard regimen: 200 mg on the first day followed by 100 mg daily for 5-10 days. In the course of observations, clinical and laboratory signs of adverse events were reported. Venous blood samples were collected from each patient for pharmacogenetic studies. Genotyping was performed using the real-time polymerase chain reaction technique. Statistical analysis: вata were analysed by using IBM SPSS Statistics, Version 23.0.

Results

Results. There were no significant associations of carriage of various CES1 variants with the frequency of adverse reactions (bradycardia, nausea, vomiting) and laboratory markers of adverse events (ALT, AST, creatinine levels).

Conclusion

Conclusion. In our study, no association was found between the carriage of CES1 gene polymorphisms and the safety parameters of remdesivir in hospitalized patients with COVID-19. Further research into the possibilities of personalizing COVID-19 therapy through pharmacogenetic testing is needed.

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The authors declare that there are no conflicts of interest present.