pmedpharmФармация и фармакологияPharmacy & Pharmacology2307-92662413-2241Pyatigorsk Medical and Pharmaceutical Institute - branch of Volgograd State Medical Univer10.19163/2307-9266-2024-12-3-209-218pmedpharm-1610Research ArticleОРИГИНАЛЬНАЯ СТАТЬЯRESEARCH ARTICLEОценка риска возникновения вторичных бактериальных инфекций у больных COVID-19 при приёме противовоспалительных генно-инженерных биологических препаратовRisk of secondary bacterial infections during treatment with anti-inflammatory genetically engineered biological drugs in COVID-19 patientshttps://orcid.org/0000-0002-0258-4092ПетровВ. И.PetrovV. I.

доктор медицинских наук, профессор, заведующий кафедрой клинической фармакологии и интенсивной терапии ФГБОУ ВО ВолгГМУ Минздрава России; главный внештатный специалист – клинический фармаколог Министерства здравоохранения РФ; заслуженный деятель науки РФ; заслуженный врач РФ; академик РАН.

400131, Россия, г. Волгоград, пл. Павших Борцов, д. 1

Doctor of Sciences (Medicine), Professor, Head of the Department of Clinical Pharmacology and Intensive Care of Volgograd State Medical University; chief freelance specialist; clinical pharmacologist of the Ministry of Healthcare of the Russian Federation; Honored Scientist of the Russian Federation; Honored Doctor of the Russian Federation; Academician of RAS. 

1 Pavshikh Bortsov Sq., Volgograd, Russia, 400131

brain@sprintnet.ruhttps://orcid.org/0000-0002-4778-5015РязановаА. Ю.RyazanovaA. Yu.

кандидат медицинских наук, доцент кафедры клинической фармакологии и интенсивной терапии ФГБОУ ВО ВолгГМУ Минздрава России

400131, Россия, г. Волгоград, пл. Павших Борцов, д. 1

Candidate of Sciences (Medicine), Associate Professor at the Department of Clinical Pharmacology and Intensive Care of Volgograd State Medical University. 

1 Pavshikh Bortsov Sq., Volgograd, Russia, 400131

nastasyakus@mail.ruhttps://orcid.org/0000-0002-2578-6228ТокареваН. С.TokarevaN. S.

ассистент, аспирант кафедры клинической фармакологии и интенсивной терапии ФГБОУ ВО ВолгГМУ Минздрава России.

400131, Россия, г. Волгоград, пл. Павших Борцов, д. 1

assistant, postgraduate student of the Department of Clinical Pharmacology and Intensive Care of Volgograd State Medical.

1 Pavshikh Bortsov Sq., Volgograd, Russia, 400131

nata5847@yandex.ruФедеральное государственное бюджетное образовательное учреждение высшего образования «Волгоградский государственный медицинский университет» Министерства здравоохранения Российской Федерации.РоссияVolgograd State Medical UniversityRussian Federation202411032025123209218Copyright © Петров В.И., Рязанова А.Ю., Токарева Н.С., 20252025Петров В.И., Рязанова А.Ю., Токарева Н.С.Petrov V.I., Ryazanova A.Y., Tokareva N.S.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.pharmpharm.ru/jour/article/view/1610Цель

Цель. Выявить наличие и степень выраженности связи между применением противовоспалительных генно-инженерных биологических препаратов и развитием вторичных бактериальных инфекций у больных COVID-19.

Материалы и методы

Материалы и методы. Проанализировано 1296 медицинских карт пациентов, госпитализированных с диагнозом COVID-19 в сентябре 2020 года, марте, сентябре 2021 года, марте, сентябре и ноябре 2022 г. Выполнено исследование «случай-контроль» с использованием метода подбора пар «matched case-control study» (275 пар), идентичных по полу, возрасту (±2 года), степени тяжести поражения лёгких по данным компьютерной томографии / рентгенографии лёгких, исходу COVID-19, сопутствующими нарушениями углеводного обмена. В качестве «случая» были представлены пациенты с признаками вторичной бактериальной инфекции (по показателям: лейкоциты ≥12×109/л, прокальцитонин ≥0,5 нг/мл и/или вирусно-бактериальная пневмония по данным аутопсии). В качестве «контроля» были пациенты без признаков бактериальной инфекции (лейкоциты <11×109/л, прокальцитонин <0,5 нг/мл, отсутствие описания клинических признаков бактериальной инфекции в медицинской карте на протяжении всей госпитализации). Для указанных групп исследовали назначения 6 противовоспалительных генно-инженерных биологических препаратов (ГИБП): тоцилизумаб, сарилумаб, олокизумаб, левилимаб, нетакимаб, секукинумаб.

Результаты

Результаты. Применение любого противоспалительного ГИБП было ассоциировано с появлением признаков вторичной бактериальной инфекции (ОШ=2,41; 95% ДИ от 1,54 до 3,77; р <0,001): для левилимаба ОШ составило 3,44 (95% ДИ от 1,64 до 7,23; р <0,001), для тоцилизумаба – ОШ=1,75 (95% ДИ от 0,73 до 4,17; р=0,201), для олокизумаба – ОШ=1,28 (95% ДИ от 0,81 до 2,03; р=0,292).

Заключение

Заключение. Среди трёх препаратов (тоцилизумаб, олокизумаб, левилимаб) наибольшей безопасностью в отношении предупреждения признаков вторичной бактериальной инфекции был препарат олокизумаб. Стоит отметить, что требуется дальнейшее изучение риска развития бактериальных осложнений у пациентов с COVID-19 на фоне применения противовоспалительных ГИБП.

The aim of the work was to identify the presence and strength of association between the use of anti-inflammatory genetically engineered biological drugs and the development of secondary bacterial infections in COVID-19 patients.

Materials and methods

Materials and methods. We used 1 296 medical records of patients hospitalized in the infectious diseases hospital of the Volgograd region with a diagnosis of COVID-19 in September 2020, March and September 2021, March, September and November 2022, have been analyzed. A matched case-control study was performed with 275 pairs identical in gender, age (±2 years), the severity of the lung damage according to computed tomography / chest X-ray, a COVID-19 outcome, concomitant carbohydrate metabolism disorders. Patients with the signs of the secondary bacterial infection (leukocytes ≥12×109/l, procalcitonin ≥0.5 ng/ml and/or viral-bacterial pneumonia according to the autopsy data) were presented as a case. The “control” group included patients without signs of any bacterial infection (leukocytes <11×109/l, procalcitonin <0.5 ng/ml, no description of clinical signs of the bacterial infection in the medical record during the hospitalization). The prescription of 6 anti-inflammatory genetically engineered biological drugs (tocilizumab, sarilumab, olokizumab, levilimab, netakimab, secukinumab) has been studied for these groups.

Results

Results. The use of any anti-inflammatory genetically engineered biological drug was associated with the development of the secondary bacterial infection signs (OR=2.41; 95% CI: from 1.54 to 3.77; p <0.001): for levilimab, the OR was 3.44 (95% CI: from 1.64 to 7.23; p <0.001), for tocilizumab – OR=1.75 (95% CI: from 0.73 to 4.17; p=0.201), for olokizumab – OR=1.28 (95% CI: from 0.81 to 2.03; p=0.292).

Conclusion

Conclusion. Among the three drugs (tocilizumab, olokizumab, levilimab), the Russian biosimilar olokizumab, a monoclonal antibody to circulating interleukin-6, has shown itself as the safest drug in terms of preventing the secondary bacterial infection signs. Further studies of developing bacterial complications risk in COVID-19 patients receiving anti-inflammatory genetically engineered biological drugs are required.

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