ABSTRACT
As the coronavirus disease 2019 (COVID-19) pandemic is ongoing and new variants of severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) are emerging, there is an urgent need for COVID-19 vaccines to control disease outbreaks by herd immunity. Surveillance of rare safety issues related to these vaccines is progressing, since more granular data emerge with regard to adverse events of COVID-19 vaccines during post-marketing surveillance. Interestingly, four cases of anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) presenting with pauci-immune crescentic glomerulonephritis (GN) after COVID-19 mRNA vaccination have already been reported. We here expand our current knowledge of this rare but important association and report a case of AAV presenting with massive rhabdomyolysis and pauci-immune crescentic GN after Pfizer-BioNTech COVID-19 mRNA vaccination. As huge vaccination programs are ongoing worldwide, post-marketing surveillance systems must continue to assess vaccine safety important for the detection of any events associated with COVID-19 vaccination. This is especially relevant in complex diseases where diagnosis is often challenging, as in our patient with AAV presenting with massive rhabdomyolysis and pauci-immune crescentic GN.
Subject(s)
Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis/pathology , COVID-19 Vaccines/adverse effects , Glomerulonephritis/pathology , Rhabdomyolysis/pathology , Aged , Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis/diagnosis , Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis/immunology , Antibodies, Antineutrophil Cytoplasmic/blood , Antibodies, Antineutrophil Cytoplasmic/immunology , BNT162 Vaccine , COVID-19/prevention & control , COVID-19 Vaccines/immunology , Female , Glomerulonephritis/diagnosis , Glomerulonephritis/immunology , Humans , RNA, Messenger/immunology , Rhabdomyolysis/diagnosis , Rhabdomyolysis/immunologyABSTRACT
A relationship is emerging between SARS-CoV-2 infections and ANCA-associated vasculitis (AAV) because: (i) the pulmonary involvement of COVID-19 may mimic that observed in patients with AAV; (ii) the two diseases may occur together; (iii) COVID-19 may trigger AAV. However, few cases of AAV have been identified so far in COVID-19 patients. To define the frequency of ANCA autoimmunity in patients with SARS-CoV-2 infection, we analyzed the serum ANCAs and the serum PR3 and MPO antigens by immunoassays in 124 adult patients with a diagnosis of SARS-CoV-2 infection (16 were asymptomatic and 108 were hospitalized) and 48 control subjects. The serum ANCAs were significantly higher in the hospitalized patients compared with either the controls or the asymptomatic patients and increased with the progression of the COVID-19 severity. After one week of hospitalization, the values were significantly lower. In contrast, no differences emerged among the controls, asymptomatic and hospitalized patients for the PR3 and MPO serum levels. None of the patients had clinical signs of AAV with the exception of a severe pulmonary involvement. Further studies are necessary to define whether the increase in the serum ANCAs might mask subclinical vasculitis in a percentage of patients with SARS-CoV-2 infection or it is an epiphenomenon of SARS-CoV-2 infection with no clinical manifestations.
Subject(s)
Antibodies, Antineutrophil Cytoplasmic/blood , COVID-19/blood , COVID-19/virology , SARS-CoV-2 , Adult , Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis/blood , Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis/diagnosis , Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis/etiology , COVID-19/diagnosis , COVID-19/immunology , Disease Susceptibility , Female , Humans , Immunoassay , Male , Middle Aged , Pilot Projects , Symptom AssessmentSubject(s)
Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis/diagnosis , Antibodies, Antineutrophil Cytoplasmic/blood , Immunoassay/standards , Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis/blood , Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis/immunology , Calibration , Data Interpretation, Statistical , Diagnosis, Differential , Humans , Immunoassay/methods , Likelihood Functions , Myeloblastin/immunology , Peroxidase/immunology , Reference Standards , Sensitivity and SpecificityABSTRACT
ANCA-associated RPGN leads to renal failure through systemic vasculitis and diffuse crescentic glomerulonephritis. MPO-ANCA-RPGN patients are highly susceptible to infections. Our aim in this study was to uncover reasons why these patients were susceptible to infections. We analyzed various aspects of type I interferon system including HVJ-stimulated IFN-α producing capacity and plasmacytoid dendritic cell (pDC) number in whole blood in MPO-ANCA-RPGN patients. Compared with healthy subjects, MPO-ANCA-RPGN patients showed impaired HVJ-stimulated IFN-α producing capacity and lower pDC number with or without glucocorticoid treatment. Immuno-histological staining of MPO-ANCA-RPGN kidney samples revealed a few but apparent pDC in T cell infiltrating regions even in patients with low pDC number in their peripheral blood. Patients' low HVJ-stimulated IFN-α producing capacity and pDC numbers persisted even after patients underwent several years of treatment. Former infection was determined using patients' serum BPI, Lamp-2 and Calprotectin, since they are reflective of a history of infection. These markers were higher in MPO-ANCA-RPGN patients than in healthy subjects. These results indicate that impaired HVJ-stimulated IFN-α production as well as dysfunction of the IFN system might have resulted from a previous bout of infection and can be partially implicated in patients' long-term susceptibility and vulnerability to infection.