Mild COVID-19 in ANCA-associated vasculitis treated with rituximab

Abstract

Treatment for antineutrophil cytoplasmic antibody (ANCA)associated vasculitis usually raises questions about the risk of infections. Particular attention has been given to the impact of drugs such as cyclophosphamide and B-cell depletory therapies on the severity of COVID-19. Monti et al 1 suggest that receiving biological disease-modifying antirheumatic drugs may not increase risk of COVID-19. Furthermore, Guilpain et al 2 reported a woman treated with rituximab and low-dose prednisone due to granulomatosis with polyangeitis proteinase 3-antineutrophil cytoplasmic antibody (PR3-ANCA) vasculitis, who developed pneumonia associated with COVID-19 with a milder evolution than expected in other series. Here, we present a 64-year-old woman diagnosed of myeloperoxidase-ANCA microscopic polyangiitis in 2014, with secondary hypertrophic pachymeningitis, sinusitis and constitutional syndrome. Her main comorbidities were hypercholesterolaemia and areata alopecia. On 25 November 2019, vasculitis relapsed and was treated with two infusions of 1000 mg rituximab given 2 weeks apart, in addition to three bolus of 125 mg methilprednisolone. The patient improved and received maintenance treatment with 7.5 mg/day prednisone and a doublestrenght tablet of trimethropim-sulfamethoxazole 3 days a week. While on holidays at her daughter's house in The Netherlands, on 7 March 2020 her husband developed fever >38°C, odynophagia, discomfort and dyspnoea. He was finally admitted to a hospital and diagnosed with COVID-19 infection by reverse transcription PCR (RT-PCR) on a nasopharyngeal swab. At the same time, she presented feverish, asthenia, myalgia, lack of appetite, headache, anosmia and dysgeusia, and was treated with paracetamol at home, improving after 2 weeks. One month later, after returning home in Spain, she came to our clinic for evaluation due to her exposure to COVID-19. Blood test results showed positive immunochromatographicspecific IgG antibodies assay for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). IgM antibodies and nasopharyngeal swab (RT-PCR) were both negative. Cytometric studies revealed 10 B lineage cells. Serum immunoglobulin showed moderately decreased IgM (0.23 g/L), and normal IgG and IgA concentrations. A test for ANCAs was positive, with a perinuclear staining pattern, and an ELISA confirmed the presence of myeloperoxidase ANCA at a titre of 5.3 U/mL (reference range <1). Patients with compromised immune systems represent a susceptible population in which infections may have devastating consequences. The impact of rituximab treatment on SARS-CoV-2 infection remains to be clarified. As hyperinflammation underlies the mechanism of severe COVID-19, the immunocompromised situation may prevent them from virus-induced cytokine storm syndrome. 3 Transcriptome data including RNA-seq and GeneChip human genome arrays show that glucocorticoids and some disease modifying anti-rheumatic drugs (DMARDs) (tocilizumab, methotrexate, hydroxychloroquine, tofacitinib, azathioprine and so on) could suppress the c...

High rates of severe disease and death due to SARS-CoV-2 infection in rheumatic disease patients treated with rituximab: a descriptive study

“…These 10 patients were from various case reports and case series. Of these 10 patients, 8 had bilateral pneumonia requiring hospitalization and supplementary oxygen and three died [9,[15][16][17][18][19][20]. All these reports suggest a possible association between rituximab treatment for RMDs and poor prognoses for SARS-CoV-2 infected patients, but no study to date has analyzed the risk of SARS-CoV-2 infection and prognosis of such patients.…”

“…SARS-CoV-2 is an enveloped, single-stranded RNA virus and a member of β-coronaviruses, such as severe acute respiratory syndrome coronavirus (SARS-CoV) and Middle East respiratory syndrome coronavirus. Similar to SARS-CoV, SARS-CoV-2 enters human cells using angiotensin-converting enzyme2 and causes coronavirus disease (COVID- 19). COVID-19 severity ranges from asymptomatic to severe, and the disease can result in acute respiratory distress syndrome (ARDS) and cytokine storm, which have led to death in 3-10% of the infected population.…”

Patient with Antineutrophil Cytoplasmic Antibody Associated Small Vessel Vasculitis, Acute Renal Failure, and Coronavirus Disease-19 Pneumonia: A Diagnostic and Therapeutic Challenge

“…The management of glomerular diseases in the COVID-19 era is changing, and there are issues whether intravenous cyclophosphamide should be substituted with peroral or rituximab should not be used at all due to longterm depletion of B cells [17]. There are recently some case reports where rituximab was used successfully in patients with AAV [18]. The most recent paper for treatment of AAV during COVID pandemics recommends plasma exchange, oral glucocorticoids, and intravenous cyclophosphamide 500 mg every 2-3 weeks in 6 doses for COVID-19 negative patients, with several options in COVID-19 positive patients [19].…”

COVID-19, rheumatic diseases and immune dysregulation—a perspective

“…Arguably, cell-mediated immunity may be more important in reducing the risk of severe CRS and COVID-19. Interestingly, a report of a COVID-19 in a patient with ANCA-associated vasculitis treated with rituximab showed mild symptoms [100]. It is clear, however, that patients treated with these agents have an increased risk of developing other infections (e.g.…”