COVID‐19 Reinfection in a Patient Receiving Immunosuppressive Treatment for Antineutrophil Cytoplasmic Antibody–Associated Vasculitis
Authors: Kavita Gulati, Maria Prendecki, Candice Clarke, Michelle Willicombe, Stephen McAdoo
Journal: Arthritis & Rheumatology (2021)

To the Editor: We recently saw a patient who presented with coronavirus disease 2019 (COVID-19) and, during hospitalization, was diagnosed as having granulomatosis with polyangiitis (GPA), an antineutrophil cytoplasmic antibody (ANCA)–associated vasculitis, which was likely present prior to COVID-19 infection. Immunosuppressive treatment for GPA may have affected her subsequent medical course, described below, which included another episode of COVID-19. The patient, a 61-year-old woman, presented in early April 2020, during the first peak of the COVID-19 pandemic, with acute-onset dry cough, dyspnea, fever, and myalgia. Findings of initial laboratory tests were suggestive of COVID-19 (neutrophil:lymphocyte ratio 10.3, platelet count 517 × 109/liter, C-reactive protein [CRP] 236 mg/liter, d-dimer 5,794 µg/liter, ferritin 528 µg/liter, troponin 881 ng/liter), and infection was confirmed by severe acute respiratory syndrome coronavirus 2 (SARS–CoV-2) polymerase chain reaction (PCR) testing of a nasopharyngeal swab. She received supportive care for COVID-19, and the fever and myalgia gradually resolved over the following 14 days. During this period, she developed progressive kidney dysfunction with urinary abnormalities (serum creatinine level increasing to 210 µmoles/liter [2.38 mg/dl] and urinary protein:creatinine ratio 132 mg/mmole), prompting immunologic testing. This revealed proteinase 3–ANCA at a titer of 141 IU/ml (normal <3). Further assessment revealed a history of ear, nose, and throat symptoms (nasal discharge, hearing loss) and weight loss over the preceding 6 months. Cross-sectional imaging showed erosive sinusitis and bilateral pulmonary nodules. Kidney biopsy revealed severe pauci-immune necrotizing glomerulonephritis, compatible with a diagnosis of GPA that likely predated her presentation with acute COVID-19. On 3 occasions starting 23 days after the initial positive test result, repeat PCR testing for SARS–CoV-2 yielded negative results, and seroconversion was confirmed by detection of IgM and IgG antibodies to the viral S-protein. Consequently treatment for GPA was initiated (rituximab [total dose 2 gm over 2 weeks], pulse intravenous cyclophosphamide [total dose 750 mg over 2 weeks], and oral glucocorticoids [starting at 30 mg/day]). She responded rapidly, with improvement in symptoms, inflammation markers (CRP 5 mg/liter), renal function (creatinine 110 µmoles/liter [1.14 mg/dl], urinary protein:creatinine ratio [<50 mg/mmole]) and a negative result on ANCA testing by July 2020. Results of serial PCR tests for SARS–CoV-2 during this period were negative, but antibodies to viral proteins were not detectable. She received maintenance therapy with prednisolone 5 mg day, with a plan for re-treatment with rituximab at 6 months. The patient presented again in October 2020, following contact with a family member who had proven COVID-19, with fever, myalgia, dyspnea, and new pulmonary infiltrates. At that time, SARS–CoV-2 PCR test results were positive on 2 occasions (3 viral targets identified), and laboratory findings were compatible with acute infection (CRP 74 mg/liter, d-dimer 1,714 µg/liter, ferritin 864 µg/liter). Her kidney function was stable, with no urinary abnormalities, and ANCA remained negative, suggesting that her vasculitis was in remission. She received supplemental oxygen, dexamethasone, and prophylactic anticoagulation and was discharged after 10 days. Results of repeat PCR and serologic testing for SARS–CoV-2 antibody were both negative 1 month following the second COVID-19 illness. Of note, peripheral B cell depletion persisted (CD19 <2/µl) following rituximab therapy in April, although total IgG levels were preserved (5.8 gm/liter). The 6-month interval between symptomatic COVID-19 illnesses, with repeated negative results on PCR testing between episodes, suggests reinfection with SARS–CoV-2; however, we cannot definitively exclude persistent viral replication in this immunocompromised patient. The case highlights that patients receiving immunosuppression treatment may develop viral reinfection or persistence (1, 2). This is important as previous reports on immunocompetent individuals suggest that the disease course may be more severe after reinfection (3, 4). Our experience also suggests that immunosuppression may impact the longevity of protective immune responses to SARS–CoV-2 infection. This may have important implications for vaccine efficacy in these at-risk patients, who are likely to be prioritized for immunization in the near future. We plan to delay further maintenance immunosuppression treatment in this patient to provide an opportunity for vaccination. Supported by the National Institute for Health Research Imperial Biomedical Research Centre. The views expressed are those of the author and not necessarily those of the NIHR or the Department of Health and Social Care. This case has been submitted to the United Kingdom and Ireland Vasculitis COVID-19 Registry. The patient provided written informed consent for publication of case details.