Patients with autoimmune diseases were largely excluded from the controlled trials of COVID-19 vaccines. As such, the interaction of vaccines with the underlying autoinflammatory state has been observed in few real-world studies.3,4 Post approval, rare but serious adverse events including vaccine induced thrombosis and thrombocytopenia (VITT) and myocarditis have been reported with adenoviral vectored and mRNA based COVID-19 vaccines.1,2,5 The inactivated vaccines in general have displayed a favourable safety profile in controlled settings. In rare circumstances, however, cardiac, and new onset musculoskeletal phenomena have been reported. We previously reported a case of hyper-eosinophilia with symptomatic myocarditis, facial, hand and ankle edema in a medical professional within days of his first dose of COVAXIN.6 New onset reactive arthritis has been observed in elderly patients after administration of the inactivated vaccine, CoronaVac.7 Flares of systemic rheumatic disease have been observed in around 15% of recipients of COVID-19 vaccines, largely the mRNA vaccines. Majority of such flares have been reported to be of moderate-severe category with some persisting for more than 3 weeks.3 To our knowledge, this is the first case of new onset rheumatoid arthritis with characteristic rheumatoid nodules post COVID-19 vaccine. The associated hyper eosinophilia was refractory to steroid therapy. Though the patient had elevated BNP levels, there were no symptoms or signs of cardiac involvement. However, subclinical myocarditis cannot be ruled out. The lady had a background history of controlled hypertension. Previously, women and those with pre-existing hypertension each have been shown to be associated with a two-times higher odds of development of adverse events following immunization.8 The mechanisms of autoimmune induction by inactivated COVID-19 vaccine needs to be delineated. It can be related to the aluminium hydroxide adjuvant present in the vaccine. Autoimmune/inflammatory syndromes induced by adjuvant (ASIA) was first described in 2011 by Shoenfeld and Agmon-Levin. Aluminium in adjuvants is known to cause preferential Th2 based IL-5 stimulation that can explain hyper eosinophilia and autoantibodies seen in the patient. The musculoskeletal inflammation can also be explained by the NOD-like receptor protein family 3 (NLRP3) driven release of IL-1 and IL-18 by aluminium. Persons with certain HLA alleles such as HLA-DRB1 might be at increased risk.9 Auto-antibodies generated as a response to viral proteins due to cross-reactivity, and direct toxicity by the Spike or other viral proteins, may be other tentative pathogenetic pathways.10
The case is interesting as the first reported case of a new onset connective tissue disorder following inactivated COVID-19 vaccine administration. The rapidity of disease progression including appearance of rheumatoid nodules is another atypical feature of this case. Focused research is needed on autoimmune complications resulting from COVID-19 vaccines, and there is also a constant need to update guidelines for vaccinating patients with autoimmune conditions using diverse vaccine types, including the updating of potential contraindications.