SARS-CoV-2 breakthrough infections among vaccinated individuals with rheumatic disease: results from the COVID-19 Global Rheumatology Alliance provider registry.

OBJECTIVE: While COVID-19 vaccination prevents severe infections, poor immunogenicity in immunocompromised people threatens vaccine effectiveness. We analysed the clinical characteristics of patients with rheumatic disease who developed breakthrough COVID-19 after vaccination against SARS-CoV-2. METHODS: We included people partially or fully vaccinated against SARS-CoV-2 who developed COVID-19 between 5 January and 30 September 2021 and were reported to the Global Rheumatology Alliance registry. Breakthrough infections were defined as occurring ≥14 days after completion of the vaccination series, specifically 14 days after the second dose in a two-dose series or 14 days after a single-dose vaccine. We analysed patients' demographic and clinical characteristics and COVID-19 symptoms and outcomes. RESULTS: SARS-CoV-2 infection was reported in 197 partially or fully vaccinated people with rheumatic disease (mean age 54 years, 77% female, 56% white). The majority (n=140/197, 71%) received messenger RNA vaccines. Among the fully vaccinated (n=87), infection occurred a mean of 112 (±60) days after the second vaccine dose. Among those fully vaccinated and hospitalised (n=22, age range 36-83 years), nine had used B cell-depleting therapy (BCDT), with six as monotherapy, at the time of vaccination. Three were on mycophenolate. The majority (n=14/22, 64%) were not taking systemic glucocorticoids. Eight patients had pre-existing lung disease and five patients died. CONCLUSION: More than half of fully vaccinated individuals with breakthrough infections requiring hospitalisation were on BCDT or mycophenolate. Further risk mitigation strategies are likely needed to protect this selected high-risk population.

Using antineutrophil cytoplasmic antibody testing to diagnose vasculitis: can test-ordering guidelines improve diagnostic accuracy?

BACKGROUND: Antineutrophil cytoplasmic antibodies (ANCAs) are strongly associated with Wegener granulomatosis, Churg-Strauss angiitis, microscopic polyangiitis, and pauci-immune glomerulonephritis, referred to collectively as ANCA-associated vasculitis (AAVs). It is unclear how accurate ANCA measurement is for diagnosing AAV in diverse populations or whether proposed ANCA test-ordering guidelines improve test performance. METHODS: We assembled a retrospective case series of hospitalized and ambulatory patients from 2 academic medical centers to assess the diagnostic accuracy of ANCA measurement by enzyme-linked immunosorbent assay in identifying cases of AAV. In addition, we assessed the effect of applying proposed ANCA test-ordering guidelines on test performance. RESULTS: For ANCA testing, sensitivity was 81%; specificity, 98%; positive predictive value, 54%; and negative predictive value, 99%. There were no significant changes in operating characteristics after applying the guideline criteria. Using guidelines would have decreased ANCA test ordering by 23% and would have decreased the false-positive rate by 27%. No cases of AAV would have been missed if only patients fulfilling the guidelines were ANCA tested. CONCLUSION: A positive result on an enzyme-linked immunosorbent assay ANCA test, as it is currently ordered, is not a definitive diagnostic indicator of AAV. Compliance with guidelines for ANCA testing would decrease the number of false-positive results and has the potential to reduce total test expenditures.