Eculizumab in treatment of ANCA-associated vasculitis complicated with Covid-19 Clinical observations

Vasculitis associated with the antineutrophilic cytoplasmic antibodies (ANCA) is an autoimmune systemic severe, often life-threatening, disease characterized by necrotizing infl ammation of small vessels. In 75-90% of cases of ANCA-associated vasculitis (AAV), a rapidly progressive pauci-immune necrotizing crescentic glomerulonephritis develops. Despite current treatment with high-dose glucocorticoids and either cyclophosphamide or rituximab, patients have a nine-fold increased mortality risk during the fi rst year of disease compared with healthy subjects. This high mortality is attributed mainly to infections and vasculitis activity. Recent data suggest that the activation of the complement system, and in particular the alternative complement pathway, plays a signifi cant role in the pathogenesis of AAV. It has been suggested that neutrophils primed by infection or pro-infl ammatory cytokines release properdin, which activates an alternative complement cascade with cleavage of C5 into C5a and C5b. Anaphylatoxin C5a binds to receptors on the surface of neutrophils, enhancing their priming and activation and thus contributing to the infl ammation. The randomized clinical trial showed that the selective C5a-receptor inhibitor avakopan was effective in the treatment of AAV. However, avacopan is currently not available in the everyday clinical practice. On the other hand, reports showing successful usage of monoclonal antibody against C5 eculizumab in severe AAV had been published. Here we present four cases of AAV complicated by COVID-19, for which conventional therapy with cy?lophosphamide could not be applied due to the particularly high risk of serious infectious complications, and eculizumab was used off-label by decision of the medical council and special commission. Taking this decision, we took into account data demonstrating the role of complement activation and, in particular, C5a in the pathogenesis of acute lung disease, induced by pathogenic viruses. Moreover, the successful usage of eculizumab in severe COVID-19 was reported recently. Thus, we sought to apply an approach aimed simultaneously at the pathogenetic mechanisms of both AAV and viral lung damage. © 2020 JSC Vidal Rus. All rights reserved.

New coronavirus infection COVID-19 in a patient after kidney allotransplantation

The article describes a clinical case of a new covid-19 coronavirus infection in a patient receiving immunosuppressive therapy after allotransplantation of a cadaveric kidney. in the present observation, the course of covid-19 was manifested by bilateral pneumonia with respiratory failure, which required the use of active therapy with antiviral drugs, complicated by a nephrotoxic effect with the correction of immunosuppressive therapy. В статье описан клинический случай новой коронавирусной инфекции COVID-19 у пациентки, получающей иммуносупрессивную терапию, после аллотрансплантации трупной почки. В настоящем наблюдении течение COVID-19 проявлялось двусторонней пневмонией с дыхательной недостаточностью, потребовавшей применения активной терапии противовирусными препаратами, осложнившейся нефротоксическим эффектом с коррекцией иммуносупрессивной терапией.