Vasculopathy in patients with severe COVID-19 infection

Т V Beketova,E V Nasonov

doi:10.30629/0023-2149-2020-98-5-325-333

Abstract

Presented review elucidates one of the manifestations of severe corona virus disease-19, (COVID-19) associated with pathological changes in the microvasculature which can be considered in the context of systemic vasculitis (SV) or vasculopathy. Since there is currently no universal treatment strategy for COVID-19, better understanding of pathomorphology and pathogenesis will provide the foundation for potentially eff ective therapeutic interventions. Along with severe progressive lung damage, patients with COVID-19 often have multiple organ symptoms resembling SV. Evidence of complement-mediated injury in severe COVID-19 comes with C5b-9 and C4d deposition in the microvasculature of lungs and other organs, which is consistent with generalized activation of both alternative and lectin-based pathways, accompanied by damage to endothelial cells, the infl ammatory cascade, and hypercoagulation. Thus, there are arguments in favor of a number of therapeutic strategies for COVID-19. Since inhibitors of the C5 component of the complement (eculizumab, ravulizumab) is eff ective in various thrombotic microangiopathies, and the selective C5aR1 receptor inhibitor аvacopan has proven eff ective for ANCA-SV, strategy targeted at the complement system look as promising in severe COVID-19. The COVID-19 infection has been observed to induce proinfl ammatory cytokine and chemokines generation, which is associated with an unfavorable prognosis. Since interleukin-6 inhibitors are eff ective for the treatment of cytokine release syndrome in various conditions, tocilizumab and sarilumab are used in patients with severe/ catastrophic COVID-19. The relevance and potential eff ectiveness of JAK inhibitor baricitinib in COVID-19 originates from its anti-infl ammatory activity and ability to suppress the early stage of coronavirus replication. Severe COVID-19 infection can be accompanied by generalized vascular pathology, mainly the microvascular, and thrombophilia, which should be considered when planning new treatment strategies.

Highlights

Представлен обзор литературы, посвященной одному из проявлений коронавирусной инфекции тяжелого течения, к которым относят патологические изменения в сосудах микроциркуляции, что можно рассматривать в рамках системного васкулита (СВ) или васкулопатии
Presented review elucidates one of the manifestations of severe corona virus disease-19, (COVID-19) associated with pathological changes in the microvasculature which can be considered in the context of systemic vasculitis (SV) or vasculopathy
Evidence of complement-mediated injury in severe COVID-19 comes with C5b-9 and C4d deposition in the microvasculature of lungs and other organs, which is consistent with generalized activation of both alternative and lectin-based pathways, accompanied by damage to endothelial cells, the inflammatory cascade, and hypercoagulation

Summary

Introduction

Представлен обзор литературы, посвященной одному из проявлений коронавирусной инфекции (corona virus disease-19, COVID-19) тяжелого течения, к которым относят патологические изменения в сосудах микроциркуляции, что можно рассматривать в рамках системного васкулита (СВ) или васкулопатии. Получены доказательства при COVID-19 тяжелого течения участия системы комплемента с отложениями в сосудах микроциркуляции легких и других органов C5b-9 и C4d, свидетельствующего об активации альтернативного и лектинового путей, что сопровождается повреждением эндотелиальных клеток, каскадом воспалительных реакций и тромбофилией. Поскольку при различных тромботических микроангиопатиях эффективна стратегия, направленная на систему комплемента, появляются основания обсуждать перспективы применения для лечения COVID-19 тяжелого течения ингибиторов С5-компонента комплемента экулизумаба, равулизумаба и селективного ингибитора рецептора С5аR1 авакопана, в клинических исследованиях доказавшего свою эффективность при АНЦА-СВ как альтернатива глюкокортикоидам.

Results

Conclusion