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Outcomes of COVID-19 in patients with ANCA-associated vasculitis receiving avacopan
  1. Faten Aqeel1,
  2. Reza Zonozi2,3,
  3. Anushya Jeyabalan2,3,
  4. Gabriel Sauvage4,
  5. John L Niles4 and
  6. Duvuru Geetha1
  1. 1Department of Medicine, Johns Hopkins University, Baltimore, Maryland, USA
  2. 2Vasculitis and Glomerulonephritis Center, Division of Nephrology, Massachusetts General Hospital, Boston, Massachusetts, USA
  3. 3Department of Medicine, Harvard Medical School, Boston, Massachusetts, USA
  4. 4Department of Medicine, Massachusetts General Hospital, Boston, Massachusetts, USA
  1. Correspondence to Dr Duvuru Geetha; dgeetha1{at}

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The complement C5a-C5a receptor (C5aR) signalling axis plays a crucial role in the pathogenesis of both antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) and COVID-19. Complement components such as the membrane attack complex, C5a, C3a and factor B are higher in patients with active AAV compared with healthy controls.1 Similarly, experimental studies have shown abundant expression of C5aR1 and increased levels of soluble C5a in severe COVID-19.2 Following the ADVOCATE trial, avacopan, a C5aR antagonist, has been approved by the US Food and Drug Administration (FDA) as an adjunct therapy for remission induction in AAV.3 Similarly, vilobelimab, an anti-C5a monoclonal antibody, was granted Emergency Use Authorization by the FDA for severe COVID-19 based on the results of the PANAMO study.4 The risk of severe COVID-19 is increased in patients receiving rituximab and high-dose glucocorticoids.5

Here, we report the outcomes of eight patients with AAV treated with avacopan who developed COVID-19, which to our knowledge has not been reported to date. We retrospectively identified patients ≥18 years old with AAV at the Johns Hopkins Vasculitis Center in Baltimore, Maryland and the Vasculitis and Glomerulonephritis Center at the Massachusetts General Hospital in Boston, Massachusetts who contracted COVID-19 while on avacopan. Data on ANCA serotype, concomitant immunosuppressive drug use, COVID-19 severity, treatment and vaccination status were retrieved.

Patient characteristics are outlined in table 1. All patients were previously vaccinated against COVID-19. The timing of vaccination in relation to B cell depletion is outlined in table 1. Spike antibody levels prior to this episode of COVID-19 were positive (n=3), negative (n=1) or not tested (n=4). The median (IQR) time from the start of induction therapy to avacopan initiation was 15 (10–30) days. The median (IQR) time from the start of induction therapy to COVID-19 infection was 116 (75–161) days. The median (IQR) time from avacopan initiation to COVID-19 was 78 (59–149) days. In addition to avacopan, induction treatment included rituximab+cyclophosphamide+glucocorticoids (n=6) and rituximab+glucocorticoids (n=2). Concomitant immunosuppression at the time of COVID-19 infection included rituximab (n=8), prednisone (n=2) and oral cyclophosphamide (n=1). All patients remained on their treatment, but cyclophosphamide was held. Two patients did not receive COVID-19 treatment, while the remainder received nirmatrelvir/ritonavir (n=3), bebtelovimab (n=1), molnupiravir (n=1), and remdesivir and dexamethasone (n=1). The severity of COVID-19 was mild in all patients except for one who was hospitalised and died from acute on chronic respiratory failure secondary to severe COVID-19 on a background of ANCA-related interstitial lung disease. In this patient, the diffusing capacity of the lungs for carbon monoxide was 31% predicted preceding COVID-19. Of the seven surviving patients, all recovered completely from acute COVID-19, and no patient experienced long COVID.

Table 1

Patient characteristics and details of COVID-19

Despite significant immunosuppression, COVID-19 was mild in nearly all patients with AAV receiving avacopan. The one patient with severe COVID-19 had advanced fibrotic lung disease. Larger studies with a comparator arm are needed to confirm the effects of C5aR blockade with avacopan in COVID-19.

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  • Contributors All authors contributed to data collection and to editing and writing of the letter.

  • Funding DG is supported by the Johns Hopkins Center for Innovative Medicine.

  • Competing interests DG: consultant to ChemoCentryx, GSK, Otsuka, Calliditas, Amgen and Aurinia.

  • Provenance and peer review Not commissioned; externally peer reviewed.