Almanac of Clinical MedicineAlmanac of Clinical MedicineАльманах клинической медицины2072-05052587-9294Moscow Regional Research and Clinical Institute (MONIKI)133910.18786/2072-0505-2020-48-036Journal ArticlesСтатьиImmunomodulatory drug therapy for the disease caused by SARS-CoV-2 infection (COVID-19)Иммуномодулирующая медикаментозная терапия при заболевании, вызванном инфекцией SARS-CoV-2 (COVID-19)https://orcid.org/0000-0002-2352-4080KarateevD. E.КаратеевД. Е.
Russian Federation

Dmitry E. Karateev - MD, PhD, Head of Department of Rheumatology; Professor, Chair of Therapy, Postgraduate Training Faculty.

61/2 Shchepkina ul., Moscow, 129110, Tel.: +7 (495) 631 74 16

Каратеев Дмитрий Евгеньевич - доктор медицинских наук, заведующий отделением ревматологии, профессор кафедры терапии факультета усовершенствования врачей.

129110, Москва, ул. Щепкина, 61/2, Тел.: +7 (495) 631 74 16

dekar@inbox.ruhttps://orcid.org/0000-0002-6519-1106LuchikhinaE. L.ЛучихинаЕ. Л.
Russian Federation

Elena L. Luchikhina - MD, PhD, Leading Research Fellow, Department of Rheumatology; Associate Professor, Chair of Therapy, Postgraduate Training Faculty.

61/2 Shchepkina ul., Moscow, 129110

Лучихина Елена Львовна - кандидат медицинских наук, ведущий научный сотрудник отделения ревматологии, доцент кафедры терапии факультета усовершенствования врачей.

129110, Москва, ул. Щепкина, 61/2

eleluch@yandex.ruMoscow Regional Research and Clinical Institute (MONIKI)ГБУЗ МО Московский областной научно-исследовательский клинический институт им. М.Ф. Владимирского1909202048Supplement 1Спецвыпуск 151670609202006092020Copyright ©; 2020, Karateev D.E., Luchikhina E.L.Copyright ©; 2020, Каратеев Д.Е., Лучихина Е.Л.2020Karateev D.E., Luchikhina E.L.Каратеев Д.Е., Лучихина Е.Л.https://creativecommons.org/licenses/by/4.0https://almclinmed.ru/jour/article/view/1339

This systematic review focuses on the state-of-the-art pharmacotherapy of immune disorders in the novel coronavirus infection (COVID-19), leading to a cytokine storm and uncontrolled inflammatory response that causes severe tissue damage and multiple organ failure. A lot of theoretical, experimental and clinical data support the need for immunomodulatory (immunosuppressive) therapy for this disease. It should be emphasized that all immunomodulatory drugs for COVID-19 are prescribed off label, and the evidence base of the results of randomized trials is just being accumulated. We review the immunomodulatory therapy for COVID-19 with the following agents: glucocorticoids, hydroxychloroquine and chloro-quine, type 1 interferons, interleukin-6 antagonists (tocilizumab, sarilumab, olokizumab), interleukin-1 p inhibitor canakinumab, tumour necrosis factor inhibitors (infliximab), Janus kinase (JAK) inhibitors (tofacitinib, baricitinib, ruxolitinib), as well as drugs with other mechanisms of action (abatacept, nivolumab, tacrolimus, sirolimus, fingolimod, melphalan, cyclosporine, methotrexate). At the moment, the most reasonable is the use of interleukin-6 receptor inhibitors, intermediate and high dose glucocorticoids, and JAK inhibitors. Based on the latest data from clinical studies, especially the "Solidarity” trial, the use of hydroxychloroquine and chloroquine seems to have insufficient evidence. There are significant pathophysiological overlaps in the development of immunopathology in COVID-19 and in rheumatic diseases, and the strategy of early aggressive immunosuppressive therapy proposed by a number of researchers almost completely coincides with the current strategies for rheumatoid arthritis.

Настоящий систематический обзор посвящен современному состоянию фармакотерапии иммунных нарушений при новой коронавирусной инфекции (COVID-19), приводящих к «цитокиновому шторму» и неконтролируемой воспалительной реакции, которая служит причиной серьезного повреждения тканей и полиорганной недостаточности. Множество теоретических, экспериментальных и клинических данных подтверждают необходимость проведения иммуномодулирующей (иммуносупрессивной) терапии при этом заболевании. Подчеркнем: все иммуномодулирующие препараты при COVID-19 назначаются вне официально зарегистрированных показаний (англ. off-label), а доказательная база в виде результатов рандомизированных исследований только создается. Рассмотрена иммуномодулирующая терапия COVID-19 следующими препаратами: глюкокортикоиды, ги-дроксихлорохин и хлорохин, интерфероны 1-го типа, антагонисты интерлейкина-6 (тоцилизумаб, сарилумаб, олокизумаб), ингибитор интерлейкина-ip канакинумаб, ингибиторы фактора некроза опухоли-альфа (инфликсимаб), ингибиторы янус-киназ (тофацитиниб, барицитиниб, руксолитиниб), а также препаратами с другими механизмами действия (абатацепт, ниволумаб, такролимус, сиролимус, финголимод, мелфалан, циклоспорин, метотрексат). На данный момент наиболее целесообразным можно признать применение ингибиторов рецепторов интерлейкина-6, глюкокортикоидов в средних и высоких дозах, ингибиторов янус-киназ. Применение гидроксихлорохина и хлорохина в свете последних данных клинических исследований, особенно исследования "Solidarity”, представляется недостаточно обоснованным. Имеется значительное патогенетическое сходство в развитии иммунопатологии при COVID-19 и ревматических заболеваниях, а стратегия ранней агрессивной иммуносупрессивной терапии, предлагаемая рядом исследователей для терапии новой коронавирусной инфекции, практически полностью совпадает с современной стратегией лечения ревматоидного артрита.

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