Outcomes of COVID-19 in patients with ANCA-associated vasculitis receiving avacopan

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. Data on ANCA serotype, concomitant immunosuppressive drug use, COVID-19 severity, treatment and vaccination status were retrieved. 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 ID Age, sex ANCA serotype Concomitant immunosuppressant at the time of COVID-19 Vaccination status Spike antibody level* Prevailing COVID-19 variant Days from induction treatment to COVID-19 COVID-19 treatment COVID-19 severity Outcome Long COVID 1 83F MPO RTX 3 mRNA doses during BCD Positive Omicron 165 Nirmatrelvir/ritonavir Mild Resolved No 2 54F PR3 RTX 3 mRNA doses preceding BCD NT Omicron 77 Nirmatrelvir/ritonavir Mild Resolved No 3 71M PR3 RTX 2 mRNA doses preceding BCD, 1 mRNA dose after BCD Positive Omicron 160 Molnupiravir Mild Resolved No 4 81M PR3 RTX, CYC prednisone 15 mg 3 mRNA doses preceding BCD NT Omicron 55 Remdesivir, dexamethasone Severe Death No 5 58F MPO RTX prednisone 5 mg 2 mRNA doses preceding BCD NT Omicron 123 None Mild Resolved No 6 58F MPO RTX 3 mRNA doses preceding BCD Positive Omicron 108 Bebtelovimab Mild Resolved No 7 75M MPO RTX 2 mRNA doses preceding BCD, 1 mRNA dose after BCD Negative Omicron 280 None Mild Resolved No 8 34M MPO RTX 3 mRNA doses preceding BCD NT Omicron 67 Nirmatrelvir/ritonavir Mild Resolved No *Positive spike antibody levels preceding this episode of COVID-19 resulted from either vaccination or prior infection during peripheral B cell presence, or through prior receipt of tixagevimab/cilgavimab.