pulmoПульмонологияPULMONOLOGIYA0869-01892541-9617Scientific and Practical Journal “PULMONOLOGIYA” LLC10.18093/0869-0189-2023-33-4-472-487pulmo-4189Research ArticleОРИГИНАЛЬНЫЕ ИССЛЕДОВАНИЯORIGINAL STUDIESВлияние раннего назначения тоцилизумаба на прогрессирование дыхательной недостаточности у пациентов с COVID-19Impact of early tocilizumab administration on the progression of respiratory failure in COVID-19 patientshttps://orcid.org/0000-0002-3174-5000МержоеваЗ. М.MerzhoevaZ. M.

Мержоева Замира Магомедовна — кандидат медицинских наук, ассистент кафедры пульмонологии ФГАОУ ВО «ПМГМУ им. И.М. Сеченова» МЗ РФ (Сеченовский Университет); научный сотрудник ФГБУ «НИИ пульмонологии» ФМБА.

119048, Москва, ул. Трубецкая, 8, стр. 2; 115682, Москва, Ореховый бульвар, 28

тел.: (499) 246-76-83

Zamira M. Merzhoeva - Candidate of Medicine, Assistant, Department of Pulmonology, Federal State Autonomous Educational Institution of Higher Education I.M. Sechenov First Moscow State Medical University of the Ministry of Health of the Russian Federation (Sechenov University); Researcher, Federal State Budgetary Institution “Pulmonology Scientific Research Institute” under Federal Medical and Biological Agency of Russian Federation.

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zamira.merzhoeva@bk.ruhttps://orcid.org/0000-0002-1484-092XЯрошецкийА. И.YaroshetskiyA. I.

Ярошецкий Андрей Игоревич — доктор медицинских наук, профессор кафедры пульмонологии.

119048, Москва, ул. Трубецкая, 8, стр. 2

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Andrey I. Yaroshetskiy - Doctor of Medicine, Professor, Department of Pulmonology, Federal State Autonomous Educational Institution of Higher Education I.M. Sechenov First Moscow State Medical University of the Ministry of Health of the Russian Federation (Sechenov University).

Trubetskaya ul. 8, build. 2, Moscow, 119048

tel.: (495) 395-63-93

dr.intensivist@gmail.comhttps://orcid.org/0000-0001-9642-5377СавкоС. А.SavkoS. A.

Савко Сергей Алексеевич — студент VI курса Института клинической медицины имени Н.В. Склифосовского.

119048, Москва, ул. Трубецкая, 8, стр. 2

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Sergey A. Savko - 6th year student, Federal State Autonomous Educational Institution of Higher Education I.M. Sechenov First Moscow State Medical University of the Ministry of Health of the Russian Federation (Sechenov University).

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bodybagontheriver@mail.ruhttps://orcid.org/0000-0001-6986-1368КраснощековаА. П.KrasnoshchekovaA. P.

Краснощекова Анна Павловна — врач анестезиолог-реаниматолог Университетской клинической больницы № 4 Клинического центра.

119048, Москва, ул. Трубецкая, 8, стр. 2

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Anna P. Krasnoshchekova - Anesthesiologist-Resuscitator, University Clinical Hospital No.4, Clinical Center, Federal State Autonomous Educational Institution of Higher Education I.M. Sechenov First Moscow State Medical University of the Ministry of Health of the Russian Federation (Sechenov University).

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krasnoshechka@icloud.comhttps://orcid.org/0000-0001-9437-6591МандельИ. А.MandelI. A.

Мандель Ирина Аркадьевна — кандидат медицинских наук, доцент кафедры анестезиологии-реаниматологии ФГАОУ ВО «ПМГМУ им. И.М. Сеченова» МЗ РФ (Сеченовский Университет); врач анестезиолог-реаниматолог Центра анестезиологии, реанимации и интенсивной терапии ФГБУ «ФНКЦ специализированных видов медицинской помощи и медицинских технологий ФМБА».

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Irina A. Mandel - Candidate of Medicine; Associate Professor, Department of Anesthesiology and Resuscitation, Federal State Autonomous Educational Institution of Higher Education I.M. Sechenov First Moscow State Medical University of the Ministry of Health of the Russian Federation (Sechenov University); Anesthesiologist-Resuscitator, Center for Anesthesiology, Resuscitation and Intensive Care, Federal State Budgetary Institution “Federal Scientific and Clinical Center for Specialized Types of Medical Care and Medical Technologies of the Federal Medical and Biological Agency of Russia”.

Trubetskaya ul. 8, build. 2, Moscow, 119048; Orekhovyy bul’var 28, Moscow, 115682

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irina.a.mandel@gmail.comhttps://orcid.org/0000-0001-9357-4924ЦареваН. А.TsarevaN. A.

Царева Наталья Анатольевна — кандидат медицинских наук, доцент кафедры пульмонологии Института клинической медицины имени Н.В. Склифосовского ФГАОУ ВО «ПМГМУ им. И.М. Сеченова» МЗ РФ (Сеченовский Университет); заведующая лабораторией ФГБУ «НИИ пульмонологии» ФМБА.

119048, Москва, ул. Трубецкая, 8, стр. 2; 115682, Москва, Ореховый бульвар, 28

тел.: (495) 395-63-93

Natal'ya A. Tsareva - Candidate of Medicine, Associate Professor, Department of Pulmonology, N.V. Sklifosovsky Institute of Clinical Medicine, Federal State Autonomous Educational Institution of Higher Education I.M. Sechenov First Moscow State Medical University of the Ministry of Health of the Russian Federation (Sechenov University); Head оf Laboratory, Federal State Budgetary Institution “Pulmonology Scientific Research Institute” under Federal Medical and Biological Agency of Russian Federation.

Trubetskaya ul. 8, build. 2, Moscow, 119048; Orekhovyy bul’var 28, Moscow, 115682

tel.: (495) 395-63-93

n_tsareva@mail.ruhttps://orcid.org/0000-0002-0685-4133ТрушенкоН. В.TrushenkoN. V.

Трушенко Наталья Владимировна — кандидат медицинских наук, ассистент кафедры пульмонологии Института клинической медицины имени Н.В. Склифосовского ФГАОУ ВО «ПМГМУ им. И.М. Сеченова» МЗ РФ (Сеченовский Университет), научный сотрудник научно-методического центра мониторинга и контроля болезней органов дыхания ФГБУ «НИИ пульмонологии» ФМБА.

119048, Москва, ул. Трубецкая, 8, стр. 2; 115682, Москва, Ореховый бульвар, 28

тел.: (495) 395-63-93

Natal'ya V. Trushenko - Candidate of Medicine, Assistant, Department of Pulmonology, N.V. Sklifosovsky Institute of Clinical Medicine, Federal State Autonomous Educational Institution of Higher Education I.M. Sechenov First Moscow State Medical University of the Ministry of Health of the Russian Federation (Sechenov University), Researcher, Scientific and Methodological Center for Monitoring and Control of Respiratory Diseases, Federal State Budgetary Institution “Pulmonology Scientific Research Institute” under Federal Medical and Biological Agency of Russian Federation.

Trubetskaya ul. 8, build. 2, Moscow, 119048; Orekhovyy bul’var 28, Moscow, 115682

tel.: (495) 395-63-93

trushenko.natalia@yandex.ruhttps://orcid.org/0000-0002-4726-4906НуралиеваГ. С.NuralievaG. S.

Нуралиева Галия Сериковна — кандидат медицинских наук, доцент кафедры пульмонологии Института клинической медицины имени Н.В. Склифосовского ФГАОУ ВО «ПМГМУ им. И.М. Сеченова» МЗ РФ (Сеченовский Университет); научный сотрудник лаборатории интенсивной терапии и дыхательной недостаточности ФГБУ «НИИ пульмонологии» ФМБА.

119048, Москва, ул. Трубецкая, 8, стр. 2; 115682, Москва, Ореховый бульвар, 28

тел.: (495) 395-63-93

Galiya S. Nuralieva - Candidate of Medicine, Associate Professor, Department of Pulmonology, N.V. Sklifosovsky Institute of Clinical Medicine, Federal State Autonomous Educational Institution of Higher Education I.M. Sechenov First Moscow State Medical University of the Ministry of Health of the Russian Federation (Sechenov University); Researcher, Laboratory of Intensive Care and Respiratory Failure, Federal State Budgetary Institution “Pulmonology Scientific Research Institute” under Federal Medical and Biological Agency of Russian Federation.

Trubetskaya ul. 8, build. 2, Moscow, 119048; Orekhovyy bul’var 28, Moscow, 115682

tel.: (495) 395-63-93

galia32@yandex.ruhttps://orcid.org/0000-0002-5999-2150АвдеевС. Н.AvdeevS. N.

Авдеев Сергей Николаевич — доктор медицинских наук, профессор, академик Российской академии наук, проректор по научной и инновационной работе, заведующий кафедрой пульмонологии Института клинической медицины имени Н.В. Склифосовского ФГАОУ ВО «ПМГМУ им. И.М. Сеченова» МЗ РФ (Сеченовский Университет); ведущий научный сотрудник ФГБУ «НИИ пульмонологии» ФМБА; директор Национального медицинского исследовательского центра по профилю «Пульмонология», главный внештатный специалист-пульмонолог Министерства здравоохранения Российской Федерации.

119048, Москва, ул. Трубецкая, 8, стр. 2; 115682, Москва, Ореховый бульвар, 28

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Sergey N. Avdeev - Doctor of Medicine, Professor, Academician of Russian Academy of Sciences, Vice-Rector for Research and Innovation, Head of the Department of Pulmonology, N.V. Sklifosovsky Institute of Clinical Medicine, Federal State Autonomous Educational Institution of Higher Education I.M. Sechenov First Moscow State Medical University of the Ministry of Health of the Russian Federation (Sechenov University); Leading Researcher, Federal State Budgetary Institution “Pulmonology Scientific Research Institute” under Federal Medical and Biological Agency of Russian Federation; Director, National Medical Research Center for the profile “Pulmonology”, Chief Freelance Pulmonologist of the Ministry of Health of the Russian Federation.

Trubetskaya ul. 8, build. 2, Moscow, 119048; Orekhovyy bul’var 28, Moscow, 115682

tel.: (499) 246-75-18

serg_avdeev@list.ruФедеральное государственное автономное образовательное учреждение высшего образования «Первый Московский государственный медицинский университет имени И.М. Сеченова» Министерства здравоохранения Российской Федерации (Сеченовский Университет); Федеральное государственное бюджетное учреждение «Научно-исследовательский институт пульмонологии» Федерального медико-биологического агентства РоссииРоссияFederal State Autonomous Educational Institution of Higher Education I.M. Sechenov First Moscow State Medical University of the Ministry of Health of the Russian Federation (Sechenov University); Federal State Budgetary Institution “Pulmonology Scientific Research Institute” under Federal Medical and Biological Agency of Russian FederationRussian FederationФедеральное государственное автономное образовательное учреждение высшего образования «Первый Московский государственный медицинский университет имени И.М. Сеченова» Министерства здравоохранения Российской Федерации (Сеченовский Университет)РоссияFederal State Autonomous Educational Institution of Higher Education I.M. Sechenov First Moscow State Medical University of the Ministry of Health of the Russian Federation (Sechenov University)Russian FederationФедеральное государственное автономное образовательное учреждение высшего образования «Первый Московский государственный медицинский университет имени И.М. Сеченова» Министерства здравоохранения Российской Федерации (Сеченовский Университет); Федеральное государственное бюджетное учреждение «Федеральный научно-клинический центр специализированных видов медицинской помощи и медицинских технологий Федерального медико-биологического агентства»РоссияFederal State Autonomous Educational Institution of Higher Education I.M. Sechenov First Moscow State Medical University of the Ministry of Health of the Russian Federation (Sechenov University); Federal State Budgetary Institution “Federal Scientific and Clinical Center for Specialized Types of Medical Care and Medical Technologies of the Federal Medical and Biological Agency of Russia”Russian Federation202320042023334472487Copyright © Мержоева З.М., Ярошецкий А.И., Савко С.А., Краснощекова А.П., Мандель И.А., Царева Н.А., Трушенко Н.В., Нуралиева Г.С., Авдеев С.Н., 20232023Мержоева З.М., Ярошецкий А.И., Савко С.А., Краснощекова А.П., Мандель И.А., Царева Н.А., Трушенко Н.В., Нуралиева Г.С., Авдеев С.Н.Merzhoeva Z.M., Yaroshetskiy A.I., Savko S.A., Krasnoshchekova A.P., Mandel I.A., Tsareva N.A., Trushenko N.V., Nuralieva G.S., Avdeev S.N.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://journal.pulmonology.ru/pulm/article/view/4189

Оптимальный интервал для начала терапии тоцилизумабом у пациентов с COVID-19 (COronaVIrus Disease 2019) не определен. Целью исследования явилась оценка эффективности назначения тоцилизумаба в зависимости от продолжительности стойкой гипертермии > 38 °С у пациентов с пневмонией, ассоциированной с SARS-CoV-2 (Severe Acute Respiratory Syndrome-related CoronaVirus 2), получающих терапию тоцилизумабом согласно Временным методическим рекомендациям Министерства здравоохранения Российской Федерации (версия на момент включения в исследование). Материалы и методы. В период с мая 2020 по май 2021 г. проведено ретроспективное когортное исследование с участием госпитализированных пациентов (n = 163) с SARS-CoV-2-ассоциированной пневмонией. Пациенты были ретроспективно распределены на 2 группы в зависимости от времени назначения тоцилизумаба (≤ 7 (n = 61) или ≥ 8 (n = 102) дней от начала заболевания). Результаты. У пациентов, получивших тоцилизумаб в первые 7 дней, ниже необходимость в СРАР-терапии (поддержание постоянного положительного давления в дыхательных путях (Continuous Positive Airway Pressure – СРАР)) (отношение рисков (ОР) – 0,129 (0,039–0,430); р = 0,001) на 3-и сутки после терапии тоцилизумабом; выше вероятность снижения объема поражения легких по данным компьютерной томографии > 25 % через 1 нед. после применения тоцилизумаба (OP – 1,065 (1,036–1,093); р = 0,001); ниже вероятность насыщения гемоглобина кислородом < 92 % на 3-й (OP – 0,807 (0,750–0,869); р = 0,001) и 7-й (OP – 0,825 (0,772–0,883); р = 0,001) дни после терапии тоцилизумабом. При необходимости в СРАР-терапии на 3-й день после введения тоцилизумаба каждый день задержки назначения препарата увеличивал риск неблагоприятного исхода в 18 раз (OP – 18,24 (5,328–62,438); р = 0,001). Продолжительность госпитализации была значимо ниже в группе раннего назначения препарата, чем в группе позднего назначения (10 (8,5–15) дней vs 13,5 (10–18) дня соответственно; р = 0,02). Летальность в группах была одинаковой (5 (8,2 %) vs 6 (5,9 %) пациентов соответственно; р = 0,748). Заключение. У пациентов с COVID-19 при развитии системного воспаления и поражения легких назначение тоцилизумаба в первые 7 дней от начала заболевания по сравнению с более поздним назначением может предотвратить необходимость эскалации респираторной поддержки и ускорить выздоровление.

The optimal interval for initiating tocilizumab therapy in patients with COVID-19 (COronaVIrus Disease 2019) has not been determined. The aim of the study was to evaluate the effectiveness of prescribing tocilizumab depending on the duration of persistent hyperthermia > 38 °С in patients with SARS-CoV-2 (Severe Acute Respiratory Syndrome-related CoronaVirus 2) associated pneumonia who received tocilizumab according to the Interim Guidelines of the Ministry of Health of the Russian Federation (version at the time of inclusion in the study). Methods. A retrospective cohort study was conducted in hospitalized patients (n = 163) with SARS-CoV-2-associated pneumonia from May 2020 to May 2021. Patients were retrospectively divided into 2 groups depending on the time of tocilizumab administration: ≤ 7 days (n = 61) or ≥ 8 days (n = 102) from the disease onset. Results. Patients who received tocilizumab in the first 7 days had the lower need for CPAP (Continuous Positive Airway Pressure) therapy on day 3 after tocilizumab therapy (HR (Hazard Ratio) – 0.129 (0.039 – 0.430); p = 0.001), a higher probability of a decrease in the volume of lung lesions on computed tomography > 25% a week after the use of tocilizumab (HR – 1.065 (1.036 – 1.093); p = 0.001), the lower probability of hemoglobin oxygen saturation below 92% on day 3 (HR – 0.807 (0.750 – 0.869); p = 0.001), and day 7 (HR – 0.825 (0.772 – 0.883); p = 0.001) after tocilizumab therapy. If CPAP therapy was required on day 3 after administration of tocilizumab, each day of delay in prescribing the drug increased the risk of an adverse outcome 18-fold (HR – 18.24 (5.328 – 62.438); p = 0.001). The duration of hospitalization was significantly lower in the early group than in the late group (10 (8.5 – 15) vs 13.5 (10 – 18) days, respectively; p = 0.02). The mortality was similar (5 (8.2%) vs 6 (5.9%) patients, respectively; p = 0.748). Conclusion. The administration of tocilizumab in the first seven days from the onset of the disease in patients with COVID-19 who developed systemic inflammation and lung damage may prevent the need for escalation of respiratory support and accelerate recovery compared with the later tocilizumab administration.

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