COVID-19 vaccination precipitating de novo ANCA-associated vasculitis: clinical implications.

We read with great interest the article by Fillon et al. [1] discussing a matter of arising importance—the precipitation of vasculitis associated with coronavirus disease 2019 (COVID-19) vaccination. Vaccination against COVID-19 remains the cornerstone in our battle against the pandemic and the need for herd immunity becomes increasingly important with the emergence of new variants. Despite having a good safety profile, post-marketing surveillance has demonstrated that COVID-19 vaccines may result in rare but severe adverse reactions, such as myocarditis and thrombotic thrombocytopaenia.

One major area of concern that has thus far received limited attention is the development of de novo autoimmune diseases following COVID-19 vaccination in previously well individuals. One such autoimmune condition, anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV), warrants particular interest because its presenting complaints can be very non-specific. AAV involves the inflammation of small blood vessels characterized by the presence of autoantibodies against the self-antigens in the cytoplasmic granules of neutrophils [2]. While the article by Fillon et al. [1] discusses four cases of relapsing AAV, another point of great interest that remains poorly studied is the precipitation of de novo AAV shortly after receipt of the COVID-19 vaccine.

To address gaps in knowledge regarding the association between COVID-19 vaccination and new-onset AAV, we reviewed published reports from January 2020 to January 2022 to investigate the clinical presentations, associations and outcomes of new-onset AAV precipitated by COVID-19 vaccination. Cases were included if the patients had symptom onset within 2 weeks of a previous COVID-19 vaccine dose, fulfilled the American College of Rheumatology diagnostic criteria for AAV [3-5], were previously undiagnosed with AAV and were treated with a reportable outcome. Our search found 13 cases fulfilling the criteria for de novo AAV occurring shortly after COVID-19 vaccination (Supplementary data, Table S1) [6-18].

Five cases presented with neurologic symptoms (such as headache, dizziness and even paraesthesia) [6, 8, 11, 16, 17], four cases with fever and flu-like symptoms [6, 7, 15, 16], four with weakness and fatigue [8, 11, 12, 16], three with nausea and vomiting [8-10] and three with haemoptysis [9, 14, 17]. With the exception of three patients [6, 16, 18], all remaining patients presented with acute kidney injury hallmarked by elevated serum creatinine, haematuria and proteinuria. Of interest, one patient presented with rhabdomyolysis [12], two presented with symptoms of neuritis [6, 18] and another presented with acute necrotizing granulomatous inflammation of the lungs [16].

Two cases were also observed to have underlying autoimmune risk factors: one patient had mild asthma [6], while another had seronegative arthritis and a 2-year history of undiagnosed vasculitis symptoms [8]. Eleven received a messenger RNA vaccine [6–13, 16–18], while two received a viral vector vaccine [14, 15]. AAV was precipitated in six patients after the first vaccine dose [7, 10, 14, 15, 17, 18] and in seven patients after the second [6, 8, 9, 11–13, 16].

Seven patients developed symptoms within 1 week after vaccination [6, 9, 13, 14, 16–18], with five developing them within 2 weeks [8, 10–12, 15]; the time to symptom onset was not reported for one patient [7]. All included cases were treated with steroid therapy; five patients were further treated with cyclophosphamide [7, 11, 12, 14, 15], five with rituximab [6, 8, 10, 16, 17] and two with both [9, 13]. All recovered without further complications except for one patient who required chronic haemodialysis [11].

In conclusion, COVID-19 vaccination can be associated with the development of AAV in previously well patients, with the most common symptoms being fever, nausea and vomiting, non-specific neurological symptoms and malaise. The prevalence of post-vaccination new-onset AAV is comparable between the first and second dose and the prognosis is good following prompt treatment. Most importantly, physicians should have a high index of suspicion for AAV if patients develop the above-mentioned symptoms and screening for ANCA may be warranted.

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