medsovetМедицинский СоветMeditsinskiy sovet = Medical Council2079-701X2658-5790REMEDIUM GROUP Ltd.10.21518/2079-701X-2021-10-108-111medsovet-6271Research ArticleДЕМИЕЛИНИЗИРУЮЩИЕ ЗАБОЛЕВАНИЯDEMYELINATING DISEASESКлиническое наблюдение течения COVID-19 у больных рассеянным склерозом на фоне терапии препаратом окрелизумаб: два клинических случаяClinical observation of the course of COVID-19 in patients with multiple sclerosis during ocrelizumab therapy: two clinical caseshttps://orcid.org/0000-0003-2676-452XПоповаЕ. В.PopovaE. V.

Попова Екатерина Валериевна - доктор медицинских наук, заведующая межокружным отделением рассеянного склероза, заведующая терапевтическим отделением 210/212 резервного госпиталя ВДНХ.

127015, Москва, ул. Писцовая, д. 10

Ekaterina V. Popova, Dr. Sci. (Med.), Head of the Interdistrict Department of Multiple Sclerosis, Head of Therapeutic Department 210/212 of the Exhibition of Achievements of the National Economy (EANE) Reserve Hospital.

10, Pistsovaya St., Moscow, 127015

ani_retake1@mail.ruhttps://orcid.org/0000-0002-3242-4444АлександровМ. И.AlexandrovM. I.

Александров Максим Игоревич - заведующий отделением реанимации и интенсивной терапии Перинатального центра, заведующий отделением реанимации и интенсивной 306-го резервного госпиталя ВДНХ.

127015, Москва, ул. Писцовая, д. 10

Maxim I.Alexandrov, Head of the Department of Reanimation and Intensive Care of the Perinatal Center, Head of the Reanimation and Intensive Department of the 306 EANE Reserve Hospital.

10, Pistsovaya St., Moscow, 127015

https://orcid.org/0000-0001-9102-6676ТрубниковаИ. А.TrubnikovaI. A.

Трубникова Инесса Анатальевна - кандидат медицинских наук, заведующая терапевтическим отделением, заместитель главного врача по терапии резервного госпиталя ВДНХ.

127015, Москва, ул. Писцовая, д. 10

Inessa A. Trubnikova, Cand. Sci. (Med.), Head of the Therapeutic Department, Deputy Chief Physician for Therapy of the EANE Reserve Hospital.

10, Pistsovaya St., Moscow, 127015

https://orcid.org/0000-0001-9261-2159ЗейналоваС. Р.ZeynalovaS. R.

Зейналова Светлана Рустамовна - кандидат медицинских наук, заместитель главного врача по клинико-экспертной работе, руководитель резервного госпиталя ВДНХ.

127015, Москва, ул. Писцовая, д. 10

Svetlana R. Zeynalova, Cand. Sci. (Med.), Deputy Chief Physician for Clinical Expert Work, Head of the Reserve Hospital of EANE Reserve Hospital.

10, Pistsovaya St., Moscow, 127015

Городская клиническая больница № 24РоссияCity Clinical Hospital No. 24Russian Federation202107082021010108111Copyright © Попова Е.В., Александров М.И., Трубникова И.А., Зейналова С.Р., 20212021Попова Е.В., Александров М.И., Трубникова И.А., Зейналова С.Р.Popova E.V., Alexandrov M.I., Trubnikova I.A., Zeynalova S.R.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/6271

В 2020 г. была объявлена пандемия COVID-19, и многим профессиональным медицинским сообществам пришлось пересмотреть алгоритмы ведения больных, относящихся к повышенным группам риска. Помимо таких факторов риска, как избыточная масса тела, возраст старше 65 лет, сердечно-сосудистые заболевания, сахарный диабет и бронхиальная астма, необходимо также акцентировать внимание и на других хронических заболеваниях с учетом возможной иммуносупрессивной терапии. В данной публикации представлены два клинических случая перенесенной инфекции COVID-19 больными рассеянным склерозом, находящихся на терапии препаратом окрелизумаб. В ходе заболевания у обеих пациенток развился цитокиновый шторм и проводилась терапия блокаторами ИЛ-6. Оба случая завершились выздоровлением с последующим возвращением к анти-В-клеточной терапии. С учетом механизма действия препарата окрелизумаб имеются более высокие риски инфекционных осложнений, в т. ч. и при COVID-19, однако летальность не превышает среднего уровня по популяции. Опубликованная к настоящему времени информация, возможно, послужит поводом для рассмотрения вопроса о применении расширенного интервала дозирования с целью минимизировать возможные риски инфицирования COVID-19, которые, вероятно, наиболее высоки именно в первые месяцы после инфузии.

The COVID-19 pandemic was announced in 2020, and many professional medical societies had to review their algorithms for the management of high-risk patients. In addition to risk factors such as overweight, age over 65 years, cardiovascular disease, diabetes mellitus, and bronchial asthma, other chronic diseases should also be emphasized, taking into account possible immunosuppressive therapy. This publication presents two clinical cases of COVID-19 infection in patients with multiple sclerosis treated with ocrelizumab. During the course of the disease, both patients developed a cytokine storm and were treated with IL-6 blockers. Both cases ended with recovery and a subsequent return to anti-B-cell therapy. Given the mechanism of action of ocrelizumab, there are higher risks of infectious complications, including with COVID-19, but mortality is not higher than the population average. The information published to date may serve as a reason to consider the use of extended dosing intervals to minimize the possible risks of COVID-19 infection, which are probably highest in the first months after infusion.

рассеянный склерозCOVID-19пандемияцитокиновый штормокрелизумабmultiple sclerosisCOVID-19pandemiccytokine stormocrelizumabReferencesZhou F., Yu T., Du R., Fan G., Liu Y, Liu Z. et al. Clinical Course and Risk Factors for Mortality of Adult Inpatients with COVID-19 in Wuhan, China: A Retrospective Cohort Study. Lancet. 2020;395(10229):1054-1062. https://doi.org/10.1016/s0140-6736(20)30566-3.Zhou F., Yu T., Du R., Fan G., Liu Y, Liu Z. et al. Clinical Course and Risk Factors for Mortality of Adult Inpatients with COVID-19 in Wuhan, China: A Retrospective Cohort Study. Lancet. 2020;395(10229):1054-1062. https://doi.org/10.1016/s0140-6736(20)30566-3.Guan WJ., Ni Z.Y., Hu Y., Liang W.H., Ou C.Q., He J.X. et al. Clinical Characteristics of Coronavirus Disease 2019 in China. N Engl J Med. 2020;382(18):1708-1720. https://doi.org/10.1056/NEJMoa2002032.Guan WJ., Ni Z.Y., Hu Y., Liang W.H., Ou C.Q., He J.X. et al. Clinical Characteristics of Coronavirus Disease 2019 in China. N Engl J Med. 2020;382(18):1708-1720. https://doi.org/10.1056/NEJMoa2002032.Luna G., Alping P., Burman J., Fink K., Fogdell-Hahn A., Gunnarsson M. et al. Infection Risks Among Patients With Multiple Sclerosis Treated With Fingolimod, Natalizumab, Rituximab, and Injectable Therapies. JAMA Neurol. 2020;77(2):184-191. https://doi.org/10.1001/]amaneurol.2019.3365.Luna G., Alping P., Burman J., Fink K., Fogdell-Hahn A., Gunnarsson M. et al. Infection Risks Among Patients With Multiple Sclerosis Treated With Fingolimod, Natalizumab, Rituximab, and Injectable Therapies. JAMA Neurol. 2020;77(2):184-191. https://doi.org/10.1001/]amaneurol.2019.3365.Karamyan A., Dunser M.W., Wiebe DJ., Pilz G., Wipfler P, Chroust V. et al. Critical Illness in Patients with Multiple Sclerosis: A Matched Case-Control Study. PLoS One. 2016;11(5):e0155795. https://doi.org/10.1371/journal.pone.0155795.Karamyan A., Dunser M.W., Wiebe DJ., Pilz G., Wipfler P, Chroust V. et al. Critical Illness in Patients with Multiple Sclerosis: A Matched Case-Control Study. PLoS One. 2016;11(5):e0155795. https://doi.org/10.1371/journal.pone.0155795.Thompson AJ., Banwell B.L., Barkhof F., Carroll W.M., Coetzee T., Comi G. et al. Diagnosis of Multiple Sclerosis: 2017 Revisions of the McDonald Criteria. Lancet Neurol. 2018;17(2):162-173. https://doi.org/10.1016/S1474-4422(17)30470-2.Thompson AJ., Banwell B.L., Barkhof F., Carroll W.M., Coetzee T., Comi G. et al. Diagnosis of Multiple Sclerosis: 2017 Revisions of the McDonald Criteria. Lancet Neurol. 2018;17(2):162-173. https://doi.org/10.1016/S1474-4422(17)30470-2.Авдеев С.Н., Адамян Л.В., Алексеева Е.И., Багненко С.Ф., Баранов А.А., Баранова Н.Н. и др. Временные методические рекомендации. Профилактика, диагностика и лечение новой коронавирусной инфекции (COVID-19). Версия 9 (26.10.2020). М.: Министерство здравоохранения Российской Федерации; 2020. 236 с. Режим доступа: https://static-0.minzdrav.gov.ru/system/attachments/attaches/000/052/548/original/%D0%9C%D0%A0_COVID-19_%28v.9%29.pdf.Avdeev S.N., Adamyan L.V., Alekseeva E.I., Bagnenko S.F., Baranov A.A., Baranova N.N. et al. Temporary Guidelines. Prevention, Diagnosis and Treatment of New Coronavirus Infection (COVID-19). Version 9 (10/26/2020). Moscow: Ministry of Health of the Russian Federation; 2020. 236 p. (In Russ.) Available at: https://static-0.minzdrav.gov.ru/system/attachments/attach-es/000/052/548/original/%D0%9C%D0%A0_COVID-19_%28v.9%29.pdf.McDonald W.I., Compston A., Edan G., Goodkin D., Hartung H.P, Lublin F.D. et al. Recommended Diagnostic Criteria for Multiple Sclerosis: Guidelines from the International Panel on the Diagnosis of Multiple Sclerosis. Ann Neurol. 2001;50(1):121-127. https://doi.org/10.1002/ana.1032.McDonald W.I., Compston A., Edan G., Goodkin D., Hartung H.P, Lublin F.D. et al. Recommended Diagnostic Criteria for Multiple Sclerosis: Guidelines from the International Panel on the Diagnosis of Multiple Sclerosis. Ann Neurol. 2001;50(1):121-127. https://doi.org/10.1002/ana.1032.Giovannoni G., Hawkes C., Lechner-Scott J., Levy M., Waubant E., Gold J. The COVID-19 Pandemic and the Use of MS Disease-Modifying Therapies. Mult Scler Relat Disord. 2020;39:102073. https://doi.org/10.1016/j.msard.2020.102073.Giovannoni G., Hawkes C., Lechner-Scott J., Levy M., Waubant E., Gold J. The COVID-19 Pandemic and the Use of MS Disease-Modifying Therapies. Mult Scler Relat Disord. 2020;39:102073. https://doi.org/10.1016/j.msard.2020.102073.Barzegar M., Mirmosayyeb O., Nehzat N., Sarrafi R., Khorvash F., Maghzi A.H., Shaygannejad V. COVID-19 Infection in a Patient with Multiple Sclerosis Treated with Fingolimod. Neurol Neuroimmunol Neuroinflamm. 2020;7(4):e753. https://doi.org/10.1212/NXI.0000000000000753.Barzegar M., Mirmosayyeb O., Nehzat N., Sarrafi R., Khorvash F., Maghzi A.H., Shaygannejad V. COVID-19 Infection in a Patient with Multiple Sclerosis Treated with Fingolimod. Neurol Neuroimmunol Neuroinflamm. 2020;7(4):e753. https://doi.org/10.1212/NXI.0000000000000753.Berger J.R., Brandstadter R., Bar-Or A. COVID-19 and MS Disease-Modifying Therapies. Neurol Neuroimmunol Neuroinflamm. 2020;7(4):e761. https://doi.org/10.1212/NXI.0000000000000761.Berger J.R., Brandstadter R., Bar-Or A. COVID-19 and MS Disease-Modifying Therapies. Neurol Neuroimmunol Neuroinflamm. 2020;7(4):e761. https://doi.org/10.1212/NXI.0000000000000761.Al-Ani M., Elemam N.M., Hundt J.E., Maghazachi AA. Drugs for Multiple Sclerosis Activate Natural Killer Cells: Do They Protect Against COVID-19 Infection? Infect Drug Resist. 2020;13:3243-3254. https://doi.org/10.2147/IDR.S269797.Al-Ani M., Elemam N.M., Hundt J.E., Maghazachi AA. Drugs for Multiple Sclerosis Activate Natural Killer Cells: Do They Protect Against COVID-19 Infection? Infect Drug Resist. 2020;13:3243-3254. https://doi.org/10.2147/IDR.S269797.Wolinsky J.S., Arnold D.L., Brochet B., Hartung H.P, Montalban X., Naismith R.T. et al. Long-Term Follow-Up from the ORATORIO Trial of Ocrelizumab for Primary Progressive Multiple Sclerosis: A Post-Hoc Analysis from the Ongoing Open-Label Extension of the Randomised, Placebo-Controlled, Phase 3 Trial. Lancet Neurol. 2020;19(12):998-1009. https://doi.org/10.1016/S1474-4422(20)30342-2.Wolinsky J.S., Arnold D.L., Brochet B., Hartung H.P, Montalban X., Naismith R.T. et al. Long-Term Follow-Up from the ORATORIO Trial of Ocrelizumab for Primary Progressive Multiple Sclerosis: A Post-Hoc Analysis from the Ongoing Open-Label Extension of the Randomised, Placebo-Controlled, Phase 3 Trial. Lancet Neurol. 2020;19(12):998-1009. https://doi.org/10.1016/S1474-4422(20)30342-2.Louapre C., Collongues N., Stankoff B., Giannesini C., Papeix C., Bensa C. et al. Clinical Characteristics and Outcomes in Patients With Coronavirus Disease 2019 and Multiple Sclerosis. JAMA Neurol. 2020;77(9):1079-1088. https://doi.org/10.1001/jamaneurol.2020.2581.Louapre C., Collongues N., Stankoff B., Giannesini C., Papeix C., Bensa C. et al. Clinical Characteristics and Outcomes in Patients With Coronavirus Disease 2019 and Multiple Sclerosis. JAMA Neurol. 2020;77(9):1079-1088. https://doi.org/10.1001/jamaneurol.2020.2581.Montero-Escribano P, Matias-Guiu J., Gomez-Iglesias P, Porta-Etessam J., Pytel V., Matias-Guiu JA.. Anti-CD20 and COVID-19 in Multiple Sclerosis and Related Disorders: A Case Series of 60 Patients from Madrid, Spain. Mult Scler Relat Disord. 2020;42:102185. https://doi.org/10.1016/j.msard.2020.102185.Montero-Escribano P, Matias-Guiu J., Gomez-Iglesias P, Porta-Etessam J., Pytel V., Matias-Guiu JA.. Anti-CD20 and COVID-19 in Multiple Sclerosis and Related Disorders: A Case Series of 60 Patients from Madrid, Spain. Mult Scler Relat Disord. 2020;42:102185. https://doi.org/10.1016/j.msard.2020.102185.Chaudhry F., Bulka H., Rathnam A.S., Said O.M., Lin J., Lorigan H. et al. COVID-19 in Multiple Sclerosis Patients and Risk Factors for Severe Infection. J Neurol Sci. 2020;418:117147. https://doi.org/10.1016/j.jns.2020.117147.Chaudhry F., Bulka H., Rathnam A.S., Said O.M., Lin J., Lorigan H. et al. COVID-19 in Multiple Sclerosis Patients and Risk Factors for Severe Infection. J Neurol Sci. 2020;418:117147. https://doi.org/10.1016/j.jns.2020.117147.Kuijpers T.W., Bende R.J., Baars P.A., Grummels A., Derks I.A., Dolman K.M. et al. CD20 deficiency in humans results in impaired T cell-independent antibody responses. J Clin Invest. 2010;120(1):214-222. https://doi.org/10.1172/JCI40231.Kuijpers T.W., Bende R.J., Baars P.A., Grummels A., Derks I.A., Dolman K.M. et al. CD20 deficiency in humans results in impaired T cell-independent antibody responses. J Clin Invest. 2010;120(1):214-222. https://doi.org/10.1172/JCI40231.Peeters L.M., Parciak T., Walton C., Geys L., Moreau Y., De Brouwer E. et al. COVID-19 in People with Multiple Sclerosis: A Global Data Sharing Initiative. Mult Scler. 2020;26(10):1157-1162. https://doi.org/10.1177/1352458520941485.Peeters L.M., Parciak T., Walton C., Geys L., Moreau Y., De Brouwer E. et al. COVID-19 in People with Multiple Sclerosis: A Global Data Sharing Initiative. Mult Scler. 2020;26(10):1157-1162. https://doi.org/10.1177/1352458520941485.

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