AB0670 THE COURSE AND OUTCOMES OF COVID-19 IN PATIENTS WITH ANCA-ASSOCIATED SYSTEMIC VASCULITIS, RECEIVING ANTI-B CELL THERAPY WITH RITUXIMAB

Abstract

Background:Currently, the issues of the effect of anti-B cell therapy on the risk of severe course of COVID-19 in patients (pts) with ANCA-associated vasculitis (AAV) has not been completely studied.Objectives:We present an analysis of the COVID-19 incidence and outcomes in 126 AAV pts treated with rituximab (RTX) from one rheumatology center registry.Methods:Data were collected with telephone/online surveying between 11-15th November 2020 from all 126 AAV pts (58- granulomatosis with polyangiitis, GPA; 38- microscopic polyangiitis, MPA; 22- eosinophilic granulomatosis with polyangiitis, EGPA (54% ANCA-negative); and 8- uncertain AAV). Pts age was 51 (20-81) yr, 62% women. Due to AAV activity or risk of relapse, during the pandemic RTX was prescribed in 48% pts.Results:The incidence of COVID-19 in AAV pts was 3.5% during the first 3 months of the pandemic, the course was uneventful, and all pts recovered. Since September 2020 a 4-fold increase in the incidence alongside with more severe course of COVID-19 were reported. After 8 months of the pandemic, COVID-19 was diagnosed in 21 (16.6%) pts with median age 55 yr, 57% women. COVID-19 incidence was lower in GPA (15.5%) vs MPA (21.1%) or EGPA (27.7%). The mortality rate was 14.3% (2- MPA, 1- GPA). When analyzing the 5-year survival rate of AAV pts treated with RTX, prognosis worsening was noted; in 2020 there were 3 deaths due to COVID-19, in the previous 5 years- only 2 deaths.Conclusion:Taking into account the fact the mechanisms of AAV and severe COVID-19 are largely synergistic (Table 1), primarily in the context of obstructive thromboinflammation as manifestation of acute inflammatory syndrome in COVID-19 [1], AAV can potentially contribute to the severe course of COVID-19. Anti-CD20 therapy seems to have a protective effect against severe COVID-19 [2], which, however, can be insufficient in AAV pts with active disease and multiple organ damage. Further analysis of COVID-19 cases in pts with AAV and other rheumatic diseases is exceptionally important.Table 1.Comparison of AAV and severe COVID-19ParameterAAVSevere COVID-19Lung damageHigh frequency of lung damagePossibly destructive lung damageDamage to other organsTypically affects the upper and lower airways and kidneys; Other organs can be involvedPossible extrapulmonary localizationVascular involvementSystemic necrotizing vasculitis of small vessels; In the active phase, hypercoagulationObstructive thromboinflammation of the microcirculation of lungs and extrapulmonary vessels; Increased incidence of Kawasaki syndrome during the pandemicInflammationHigh or very highVery highAutoantibodiesANCA pathogenetic roleDominant extrafollicular B cell responses; Сorrelation between SARS-CoV-2 antibody titer and severity of COVID-19; High titers of IFN-α2/ω autoantibodiesNeutrophilNeutrophils are the most important effector cells in the pathogenesisChanges in the morphology of neutrophils were noted; Netosis, the release of proteases from neutrophils promote the complement system activation, hypercoagulation, endotheliitis, production of pro-inflammatory cytokines; An increase of neutrophils in the blood and bronchoalveolar lavage fluid were notedComplementComplement is crucial in the pathogenesis; C5a receptor antagonist Avacopan efficacyActivation of alternative/lectin complement pathways; C5 antagonist Eculizumab has been reported to be effectiveTreatmentImmunosuppressants; In the active phase, anticoagulantsAnticoagulants; Glucocorticoids, pro-inflammatory cytokine antagonists, JAK inhibitors, cyclosporinePrognosisSeriousHigh mortality rate