Coronavirus disease 2019 (COVID-19) and immune-mediated inflammatory rheumatic diseases: at the crossroads of thromboinflammation and autoimmunity

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An enormous body of evidence on various aspects of the coronavirus disease 2019, COVID-19 associated with the SARS-CoV-2 virus (severe acute respiratory syndrome coronavirus-2) has been accumulated over the past year. Meanwhile, investigated relationship between COVID-19 and rheumatic immune-mediated inflammatory diseases (IMIDs) and certain identified similarities were of paramount importance. It was shown that the incidence of COVID-19 in patients with rheumatic diseases does not significantly differ from that in general population. The risk of severe course and unfavorable COVID-19 outcomes in patients with rheumatic IMIDs is significantly associated with older age and comorbidities – as in general population, and is not aggravated by preceding use of the majority of antirheumatic drugs. Gaining better insights into pathogenesis of COVID-19 provided sound prerequisites for anti-rheumatic drugs repurposing and substantiated their use for treatment of COVID-19 infection. Under current COVID-19 pandemic circumstances, accelerated development and invention of various COVID-19 vaccines offers a great hope to curb the tide of pandemic. However, the efficacy, immunogenicity, and safety of these vaccines in patients with rheumatic IMIDs must be studied in controlled clinical trials. Generally speaking, there are still numerous blind spots in our knowledge of rheumatological aspects of such a versatile and polymorphous condition as COVID-19 infection.

Section: Covid-19 -это проблема тромбовоспаления и аутоиммунитетаunclassified

COVID-19 and rheumatology: A year later

Белов¹,

Лила²

2021

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“…К ним относятся лихорадка, депрессивные и тревожные расстройства, синдром хронической усталости, артралгии, артрит, миалгии, миопатия, аутоиммунные цитопении, поражение нервной системы, кожи, интерстициальное заболевание легких (ИЗЛ) и многие другие. Предполагается, что у генетически предрасположенных индивидуумов (и в зависимости от гендерных и возрастных факторов) различные вирусные инфекции, включая SARS-CoV-2 [79,80], могут индуцировать нарушение иммунологической толерантности к аутоантигенам, ведущее к развитию аутоиммунной патологии за счет нескольких взаимодополняющих механизмов: «молекулярная мимикрия» вирусных и аутоантигенных эпитопов; процесс «распространения эпитопа» (epitope spreading); посторонняя (bystander) активация иммунного ответа; презентация «суперантигена»; стимуляция инфламмасом; нарушение синтеза ИФН типа I. Универсальный механизм мультиорганной патологии при COVID-19 и СКВ связан с развитием иммунопатологического процесса, получившего название «тромбовоспаление» («иммунотромбоз») [81][82][83]. Как при COVID-19, так и при СКВ патогенетические механизмы тромбовоспаления опосредуются комплексным синергическим взаимодействием «провоспалительных» цитокинов (и других медиаторов воспаления), компонентов системы комплемента (анафилотоксины), формированием NETs (neutrophil extracellular traps), индуцирующих активацию/повреждение эндотелиальных клеток (эндотелиопатия/эндотелиит) и тромбоцитов (тромбопатия) [82,84].…”

Section: скв и Covid-19unclassified

Problems of early diagnosis of systemic lupus erythematosus during the COVID-19 pandemic

Насонов

Попкова²,

Panafidina³

2021

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Systemic lupus erythematosus (SLE) is an autoimmune rheumatic disease of unknown etiology, characterized by overproduction of organ-nonspecific autoantibodies to various components of the cell nucleus and cytoplasm and the development of immune-inflammatory damage to internal organs. The debut of SLE is preceded by an asymptomatic period, characterized by impaired immunological tolerance to its own autoantigens, determined by the multifaceted interaction of external, genetic and epigenetic factors, hormonal disorders, microbiome pathology, stress effects, etc. Development of a certain spectrum of clinical symptoms characteristic of SLE along with the detection of a reflects the progression of the immunopathological process in SLE, however, there is no generally accepted term that defines the patient’s condition, which has individual serological and clinical signs characteristic of this disease. In rheumatology, the concept of «incomplete» SLE is currently most often used. The problems of early diagnosis of SLE, clinical and laboratory predictors of the transformation of “incomplete” SLE into “reliable” SLE, difficulties in diagnosing SLE during the COVID-19 pandemic are considered. Particular attention is paid to the comparative characteristics of the immunopathological mechanisms of SLE and COVID-19.

“…Еще одним обстоятельством, повышающим интерес к АНЦА-СВ в контексте коронавирусной инфекции (табл. 1), является близость представлений о патологических процессах, характеризующих АНЦА-СВ, и новой концепции MicroCLOTS (microvascular COVID-19 lung vessels obstructive thromboinflammatory syndrome; синдром обструктивного тромбовоспаления сосудов микроциркуляции легких при COVID-19) как проявлении острого воспалительного синдрома при COVID-19 тяжелого/катастрофического течения с поражением как легких, так и других различных органов и систем [5][6][7][8].…”

Section: The Course and Outcomes Of Covid-19 In Patients With Anca-asunclassified

“…Кроме того, в последнее время все больше сближаются подходы в лечении -с назначением при тяжелом/катастрофическом течении COVID-19 глюкокортикоидов, ГИБП, прежде всего ингибиторов провоспалительных цитокинов. Опубликованы сообщения об эффективном применении антагониста компонента комплемента С5 -экулизумаба, циклоспорина [7,9,[35][36][37].…”

Section: The Course and Outcomes Of Covid-19 In Patients With Anca-asunclassified

The course and outcomes of COVID-19 in patients with ANCA-associated systemic vasculitis, receiving biological therapy (Rituximab, Mepolizumab): The results of the first 8 months of the pandemic

Бекетова¹,

Babak²,

Suprun³

2021

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Objective. Currently, the issues of the effect of anti-B cell therapy or inhibitor of interleukin 5 on the risk of COVID-19 infecting and outcomes in patients with ANCA-associated vasculitis (AAV) has not been completely studied. We present an analysis of the COVID-19 course and outcomes in AAV patients treated with rituximab or mepolizumab from one rheumatology center registry. Methods. From November 11 to November 15, 2020, a cross-sectional study was conducted using telephone and online surveys, and information was collected from all 128 AAV patients treated with rituximab in V.A. Nasonova Research Institute of Rheumatology. Patients mean age was 51 (20-81) years, 61.7% were women. Granulomatosis with polyangiitis (GPA) was diagnosed in 58 patients, microscopic polyangiitis (MPA)-in 38, eosinophilic granulomatosis with polyangiitis (EGPA)-in 24 (including 54.2% of ANCA-negative cases), and AAV with uncertain nosological affiliationin 8 patients. Due to the disease activity or a high risk of AAV recurrence during the pandemic rituximab was prescribed in 60/126 (47.6%) patients, and mepolizumab-in 6 cases. Results. In the spring of the pandemic (until May 2020), the incidence of COVID-19 in AAV patients treated with rituximab was 4.3%, the disease course was relatively favorable. All patients recovered. At month 3-6, antibodies to SARS-CoV-2 IgG persisted in only 1 out of 4 patients. Since September 2020, the incidence has increased 3-fold, with a more severe course of COVID-19. In total, in the period until November 11, 2020, COVID-19 was diagnosed in 17.2% (22/128); the mean age of patients was 55 (25-81) years; 54.5% were women. 21/22 patients were on rituximab therapy, 2 patients had mepolizumab therapy (including 1 case after previous rituximab therapy). COVID-19 incidence was lower in patients with GPA (15.5%) vs MPA and EGPA (21.1% and 20.8% respectively). The mortality rate was 13.6%, including 2 patients with MPA and 1 patient with GPA. When analyzing the 5-year survival rate according to the registry of AAV patients treated with rituximab, prognosis worsening was noted; in 2020 there were 3 deaths due to COVID-19, in the previous 5 years-only 2 deaths. Discussion. Taking into account the fact the mechanisms of AAV and severe COVID-19 are largely synergistic (primarily in the context of microvascular COVID-19 lung vessels obstructive thromboinflammatory syndrome as manifestation of the acute inflammatory syndrome), the activity of AAV can potentially contribute to the disease onset and a severe course of COVID-19. Given the previously published information on the use of rituximab during the COVID-19 pandemic for various diseases, it seems that B cell depletion, without reducing the risk of infection, may have a protective effect with regard to the risk of severe/catastrophic COVID-19, which, however, can be insufficient in AAV patients. Further analysis of COVID-19 cases in patients with AAV and other immuno-inflammatory rheumatic diseases is exceptionally important.