POS1201 Incidence and outcome of COVID-19 in ANCA-associated vasculitis: impact of COVID-19 in patients undergoing rituximab for maintenance

Abstract

Background:COVID-19 is an emerging infectious disease caused by SARS-CoV-2. Risk factors for the worst outcome in COVID-19 are pre-existing pulmonary and cardiovascular disease, while the impact of chronic immunosuppression has not yet completely been clarified (1).Currently, there is no clinical evidence that chronically immunosuppressed rheumatic patients under biologic agent or a small molecule may have a higher risk of COVID-19 or a worse prognosis(2). However, the anti-CD20 antibody monoclonal rituximab may contribute to severe consequences, inhibiting the humoral response to SARS-CoV-2 and capacity to produce efficient antibodies against it (3,4). Rituximab is widely use in the treatment of ANCA-associated vasculitis (AAV). Nowadays, the incidence and impact of COVID-19 in AAV-patients are still unknown and, in particular, in AAV-patients who have been exposed to rituximab since the outbreak (5).Objectives:Herein we evaluate the incidence and outcome of SARS-CoV-2 infection in our cohort of AAV-patients who had at least one visit in the year 2020.Methods:We collected clinical data of 100 AAV-patients who had at least one visit in our Centre from February 2020 to December 2020, and we described cases of COVID-19 infection among them. The COVID-19 was proved by detection of SARS-CoV-2 RNA in nose-pharyngeal swabs. In case of infection, anti-SARS-CoV-2 IgM or IgG production was then investigated.Results:Among 100 patients (53 females; 47 males) regularly followed, the median age was 65, and the mean (SD) duration of disease was 8.8 (6.8) years. The most frequent diagnosis was granulomatosis with polyangiitis (GPA) (56%), followed by granulomatosis eosinophilic with polyangiitis (EGPA) (31%), and microscopic polyangiitis (MPA) (13%). The mean (SD) BVASv3 at the onset of disease was 12.6 (5.6). More than half of the patients (59%) have had lung and/or ENT involvement at the onset of disease. Overall, 84% of our patients received immunosuppressive agents and 45% also received glucocorticoids (GC). Rituximab was administered in 15% of patients during the pandemic. COVID-19 was diagnosed in 2 cases (2%). Both patients have received rituximab as maintenance: the last rituximab infusion was on November 9, 2020 for patient 1 (female, 73 years old, GPA ANCA-PR3+) and was on August 17, 2020 for patient 2 (female, 74 years old, MPA ANCA-MPO+). Both patients had a BVAS 0 and negative ANCA antibodies at the time of the first positive nose-pharyngeal swab RT-PCR test, on December 24 and on November 25, respectively. Both patients were B-cell depleted and IgG levels were 455 mg/dL and 866 mg/dL, respectively. While patient 1 died due to critically ill COVID-19 pneumonia 25 days after the COVID-19 disease onset, patient 2 remained asymptomatic with nose-pharyngeal swab still positive on day 56 after the first detection. Anti-SARS-CoV-2 IgM or IgG antibodies above the cut-off (cut-off value 10 AU/mL) were absent in patient 1, while in patient 2 a low level of anti-SARS-CoV-2 IgG (39 AU/mL, cut-off value 10 AU/mL) was documented.Conclusion:Prevalence of COVID-19 in AAV seems lower than in general population (prevalence of 29582/466700, 6.3%, in the same geographical area). Rituximab compromises the B-cells function and can lead to humoral immunodeficiency, causing the inability to produce anti-SARS-CoV-2 IgG antibodies. The timing of the last rituximab infusion and the levels of IgG can greatly affect the outcome. Patients who underwent anti-CD20 therapy are at higher risk of severe outcome in case of infection (3), and require prioritization for SARS-CoV-2 vaccination.