mimmunМедицинская иммунологияMedical Immunology (Russia)1563-06252313-741XSPb RAACI10.15789/1563-0625-POA-2465mimmun-2465Research ArticleОРИГИНАЛЬНЫЕ СТАТЬИORIGINAL ARTICLESПрофиль антифосфолипидных антител и состояние системы комплемента у больных COVID-19 разной степени тяжестиProfile of antiphospholipid antibodies and complement system in COVID-19 patients of different severityДолгушинаН. В.DolgushinaN. V.

Долгушина Наталия Витальевна – доктор медицинских наук, заместитель директора, руководитель департамента организации научной деятельности

Москва

Dolgushina Natalia V., PhD, MD (Medicine), Deputy Director, Head, Department of Research Management

Moscow

n_dolgushina@oparina4.ruМенжинскаяИ. В.MenzhinskayaI. V.

Менжинская Ирина Владимировна – доктор медицинских наук, ведущий научный сотрудник

117997, Москва, ул. Акад. Опарина, 4

Menzhinskaya Irina V., PhD, MD (Medicine), Leading Research Associate

117997, Moscow, Acad. Oparin str., 4

menirvl@gmail.comБезнощенкоО. С.BeznoshchenkoO. S.

Безнощенко Ольга Сергеевна – врач клинической лабораторной диагностики

Москва

Beznoshchenko Olga S., Doctor in Clinical Laboratory Diagnostics

Moscow

o_beznoshchenko@oparina4.ruМуллабаеваС. М.MullabayevaS. M.

Муллабаева Светлана Мининхаевна – врач клинической лабораторной диагностики

Москва

Mullabayeva Svetlana M., Doctor in Clinical Laboratory Diagnostics

Moscow

s_mullabaeva@oparina4.ruГородноваЕ. А.GorodnovaE. A.

Городнова Елена Александровна – кандидат медицинских наук, заведующая центром научных и клинических исследований

Москва

Gorodnova Elena A., PhD (Medicine), Head, Center for Research and Clinical Studies, Doctor in Clinical Laboratory Diagnostics

Moscow

e_gorodnova@oparina4.ruКречетоваЛ. В.KrechetovaL. V.

Кречетова Любовь Валентиновна – доктор медицинских наук, заведующая лабораторией клинической иммунологии

Москва

Krechetova Lubov V., PhD, MD (Medicine), Head, Laboratory of Clinical Immunology, Doctor in Clinical Laboratory Diagnostics

Moscow

l_krechetova@oparina4.ruФГБУ «Национальный медицинский исследовательский центр акушерства, гинекологии и перинатологии имени академика В.И. Кулакова» Министерства здравоохранения РФРоссияV. Kulakov National Medical Research Center for Obstetrics, Gynecology and PerinatologyRussian Federation202220042022242351366Copyright © Долгушина Н.В., Менжинская И.В., Безнощенко О.С., Муллабаева С.М., Городнова Е.А., Кречетова Л.В., 20222022Долгушина Н.В., Менжинская И.В., Безнощенко О.С., Муллабаева С.М., Городнова Е.А., Кречетова Л.В.Dolgushina N.V., Menzhinskaya I.V., Beznoshchenko O.S., Mullabayeva S.M., Gorodnova E.A., Krechetova L.V.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.mimmun.ru/mimmun/article/view/2465

СOVID-19 – тяжелый острый респираторный синдром, вызванный SARS-CoV-2, может предрасполагать к тромботическим событиям, особенно при сочетании с антифосфолипидными антителами (аФЛ). Однако имеются ограниченные данные о распространенности и антигенной специфичности аФЛ при COVID-19. Предполагается, что активация комплемента играет важную роль в патогенезе COVID-19-ассоциированной коагулопатии. В условиях пандемии SARS-CoV-2 необходимо выявить значимые биомаркеры для прогнозирования тяжелого течения COVID-19 и риска тромботических осложнений. Цель – оценить профиль аФЛ, количественное содержание компонентов и активность комплемента у больных с COVID-19 разной степени тяжести в динамике. С помощью ИФА в сыворотке крови определяли антитела (M, G) к кардиолипину (КЛ), фосфатидилсерину (ФС), β2-гликопротеину-I (β2-ГП-I), протромбину (ПТ), аннексину V (Ан V), компоненту комплемента C1q, содержание компонентов комплемента C3 и C4, общую активность комплемента. В исследование включили 141 больного COVID-19, группу 1 составили 39 пациентов с легкой формой, группу 2 – 65 пациентов со среднетяжелой формой, группу 3 – 37 пациентов с тяжелой формой COVID-19. Образцы крови были получены на 3-7-й день заболевания (1-я точка) и через 14-28 дней (2-я точка). аФЛ были обнаружены суммарно у 29,1% больных COVID-19, частота выявления аФЛ в группах не различалась (35,9%, 23,1% и 32,4%; p > 0,05). У 8,5% больных аФЛ обнаруживались только в 1-й точке, у 14,2% – только во 2-й точке, у 6,4% – в двух точках измерения. Более часто выявлялись антитела к ПТ (15,6%) и Ан V (11,3%). Частота выявления антител к ПТ была значимо выше, чем антител к КЛ и ФС (7,1%), β2-ГП-I (7,8%). Pаспространенность аФЛ в группах 1 и 3 не различалась. В 1-ой точке в группе 3 повышение уровня C4 (89,2%) и C3 (24,3%) в крови и снижение активности комплемента (35,1%) наблюдалось чаще, чем в группе 1. Во 2-й точке в группе 3 часто выявлялось снижение активности комплемента (59,5%). Установлено, что при уровне C3 > 720 мкг/мл риск развития тяжелой формы COVID-19 повышается в 2,6 раза, а при уровне C4 > 740 мкг/мл – в 3,3 раза. У больных COVID-19 при низкой распространенности антител к КЛ и β2-ГП-I часто обнаруживаются антитела к ПТ и Ан V. Эти антитела могут вовлекаться в патогенез COVID-19-ассоциированной коагулопатии, выявляются на поздней стадии заболевания и могут запустить АФС у предрасположенных пациентов и реконвалесцентов. Хотя аФЛ не ассоциируются с тяжестью COVID-19, персистенция аФЛ в периоде реконвалесценции может быть дополнительным фактором риска тромбоэмболических осложнений. Для больных COVID-19 характерна активация системы комплемента, возрастающая при тяжелой форме заболевания и проявляющаяся подъемом или снижением уровня компонента комплемента C3, повышением уровня С4 в крови и снижением общей активности комплемента. Определение содержания компонентов комплемента C3 и C4 в периоде прогрессирования COVID-19 имеет прогностическое значение в отношении тяжести заболевания.

 

COVID-19, a severe acute respiratory syndrome caused by SARS-CoV-2, may predispose to thrombotic events, especially when combined with antiphospholipid antibodies (aPL). However, there are limited data on prevalence and antigenic specificity of aPL in COVID-19. Complement activation is assumed to play an important role in pathogenesis of COVID-19-associated coagulopathy. During the SARS-CoV-2 pandemic, it is necessary to identify important biomarkers for predicting severe course of COVID-19 and risk of thrombotic complications. Our objective was to evaluate the aPL profile, quantitative content and activity of complement and its components in COVID-19 patients graded by severity in the course of time. IgM and IgG antibodies to cardiolipin (CL), phosphatidylserine (PS), β2-glycoprotein-I (β2-GP-I), prothrombin (PT), annexin V (An V), as well as C1q complement component, content of its C3 and C4 components and total complement activity were determined in blood serum using ELISA approach. 141 patients with COVID-19 were included in the study. Group 1 consisted of 39 patients with mild form, group 2 (65 patients) presented with moderate form, and group 3 included 37 patients with severe form of COVID-19. Blood samples were obtained on day 3-7 of the disease (1st point) and after 14-28 days (2nd point). The results were as follows: aPL were detected in 29.1% of the total COVID-19 cohort, frequency of aPL detection by the severity grade did not differ (33.3%, 24.6% and 32.4%). In 8.5% of the patients, aPL were detected only at the 1st time point; in 14.2%, only at the 2nd point; and in 6.4% of the cases, at the both time points. Antibodies to PT (16.3%) and An V (11.3%) were revealed more frequently. The detection frequency of antibodies to PT was significantly higher than antibodies to CL and PS (7.1%), β2-GP-I (7.8%). The prevalence of aPL in groups 1 and 3 did not differ. At the 1st point in group 3, increased levels of C4 (89.2%) and C3 (24.3%) in blood, and a decrease in complement activity (35.1%) were more often observed than in group 1. At the 2nd time point in group 3, a decrease in complement activity was often detected (59.5%). The C3 levels exceeding 720 μg/ml were found to predict a 2.6-fold increased risk of severe COVID-19, and this risk became 3.3 times higher at C4 levels of > 740 μg/ml. The antibodies to PT and An V are often detected in COVID-19 patients, along with low prevalence of antibodies to CL and β2-GP-I. These antibodies can be involved in pathogenesis of COVID-19-associated coagulopathy, being detectable at the late stage of the disease, and they may trigger APS in predisposed patients and reconvalescents. Although presence of aPL antibodies is not associated with COVID-19 severity, their persistence over the period of convalescence may be an additional risk factor for thromboembolic complications. The COVID-19 patients are characterized by activation of the complement system, which increases in severe cases, and manifests with increased or decreased levels of C3 complement component, increased levels of C4 component in blood, and a decreased total complement activity. Quantitative determination of C3 and C4 complement components over the period of COVID-19 progression is of prognostic value, with respect to severity of the disease.

 

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