Discussion
Local injection site reactions (swelling, itching, redness, tenderness) and systemic symptoms (fever, headache, fatigue, chills, myalgias, and arthralgias) are the most common adverse effects of all type of COVID-19 vaccines. The rare adverse reactions of COVID-19 vaccines like anaphylaxis, vaccine induced immune thrombocytopenia, thromboembolism (arterial thrombosis, cerebral venous sinus thrombosis), myocarditis, pericarditis, and Guillain-Barre-syndrome (3,4). Minimal change disease is also reported with Pfizer Biotech vaccine (5,6). Despite these adverse effects, COVID-19 vaccines are safe and effective as documented by large number of clinical trials.
Johnson & Johnson vaccine is an adenovirus vector vaccine which has human adenovirus type 26 (Ad26) vector. The vector expresses SARS-CoV-2 spike (S) antigen without virus propagation which elicits immune response to S antigen providing protection against COVID-19. Thrombotic complications associated with thrombocytopenia and Guillain-Barre syndrome are the rare reported adverse effect of Johnson & Johnson COVID-19 vaccine (7). AAV has been not reported previously as the adverse reaction of this vaccine. Here, we report a newly onset renal limited AAV in a 52 year-female after COVID-19 vaccination. She had normal renal function and laboratory parameters prior to vaccination, and this raises the suspicion of potential association between AAV and COVID-19 vaccine.
Genetic factors, infectious agents, some drugs, and environmental factors are thought to initiate the pathogenesis of AAV. There are studies suggesting the potential association between various infections and the occurrence of vasculitis (8). However, whether the infections or vaccinations are the triggering factors for autoimmune conditions like vasculitides still lacks direct evidence. A study pointed out the increased level of ANCA in patients immunized with RNA based influenza and rabies vaccine (9,10). Furthermore, there have been reports of AAV and other autoimmune conditions due to SARS-CoV-2 infections and vaccinations (mRNA COVID-19 vaccines) (11,12). Interestingly, our patient developed AAV following adenovirus vector vaccine in contrast to the reports of AAV and glomerulonephritis following m-RNA COVID-19 vaccines (1,2). The temporal causal association between autoimmune manifestations like AAV and COVID-19 vaccines can be explained by hypothesized mechanisms like molecular mimicry, defective neutrophilic apoptosis, polyclonal activation, and systemic proinflammatory cytokine response. These mechanisms are likely to trigger autoimmune responses in genetically susceptible individuals. Still there are many research going on to fill the research gap on the development of ANCA associated with COVID-19 vaccines.
There are only few case reports of AAV and ANCA glomerulonephritis developing after mRNA COVID-19 vaccination (Pfizer-BioNTech and Moderna) in the literature (1,2). AAV following adenovirus vector vaccine has not been reported previously. We believe that this is the first case report of AAV that occurred following adenovirus vector COVID-19 vaccine administration. Our patient had been immunized with Johnson and Johnson COVID-19 vaccine and developed AAV 10 days after the immunization. There have been reports of AAV after administration of influenza vaccine (10,13). So, as a lesson learnt from the past, we can speculate the neutrophilic immune response to adenovirus vector present in Johnson and Johnson vaccines, to be a potential trigger for development of AAV. Derangement in the function and expression of MPO and PR3 present in neutrophil granules have been known to cause pauci-immune vasculitis. Although this case does not conclusively clarify the causal relationship between adenovirus vector COVID-19 vaccine and AAV, further study in the future will insight the association.