key: cord-0998557-xy7o1jpc
authors: Singh, Rohit; Kaur, Upinder; Singh, Ankur; Chakrabarti, Sankha S.
title: Refractory hypereosinophilia associated with newly diagnosed rheumatoid arthritis following inactivated BBV152 COVID‐19 vaccine
date: 2022-04-09
journal: J Med Virol
DOI: 10.1002/jmv.27742
sha: d7f3ab5dc53342c911a04bea5ed6fd3dbcfd37f8
doc_id: 998557
cord_uid: xy7o1jpc

COVID-19 vaccines are considered one of the primary strategies for countering the pandemic. Inactivated SARS-CoV-2 vaccines are being manufactured in China and India. In general, they have shown better tolerability in trials. Here we report the first case of refractory hyper-eosinophilia associated with seropositive rheumatoid arthritis (RA) with rheumatoid nodules, following inactivated COVID-19 vaccine (BBV152, COVAXIN) administration. This article is protected by copyright. All rights reserved.

contributory. Further workup was performed focusing on rising eosinophil counts (>30%). Her serum immunoglobulin E (IgE) was high while stool examination was negative for parasitic ova, cysts, or atypical organisms. Despite no cardiac symptoms, the B-type natriuretic peptide levels were elevated. An upper gastrointestinal endoscopy and biopsy performed as part of evaluation for dysphagia revealed no abnormalities. A cardiac magnetic resonance imaging performed in view of multiple cases of post-vaccination myocarditis observed by us recently was also within normal limits. The patient was started empirically on oral prednisolone at a low dose of 10 mg once daily, considering a provisional diagnosis of vaccine-induced eosinophilia with asymptomatic myocarditis. This was tapered to 5 mg/day within 4 weeks and continued. Furthermore, an empirical course of albendazole-ivermectin and diethylcarbamazine was administered considering the endemicity of worm infestation and filariasis in India. Her initial complaints improved over the next 2 months while on prednisolone, but she developed a few bony nodules near both her elbow joints ( Figure S1 ). This was followed by severe pain and swelling of the bilateral elbow, wrist, metacarpophalangeal, and proximal interphalangeal joints, sparing the distal interphalangeal joints. Serology for collagen vascular diseases revealed a high titer of rheumatoid factor and anticyclic citrullinated peptide antibody. Other autoantibodies were not detected.

The patient's eosinophilia persisted, rising up to 55% on the differential count. A bone marrow aspirate was performed which revealed a hypercellular marrow with morphologically normal eosinophils, and no blasts ( Figure 1 ). Biopsy of the elbow nodules showed palisading granulomas with cores of necrobiotic collagen, consistent with rheumatoid nodules (Figure 2A ,B). The progression of the disease, medications received for short courses from local general practitioners, and sequence of investigations is shown in Table 1 . The patient was diagnosed as a case of RA. Her RA classification criteria score (American College of Rheumatology/European League Against Rheumatism) was 9/10 (breakup in Table 1 ). She was started on weekly methotrexate 7.5 mg, daily prednisolone 20 mg, and indomethacin 75 mg for pain control. The initial response in pain was significant. The patient is on follow-up and her eosinophil counts have normalized after 1 month of methotrexate therapy (absolute eosinophil count 430/µl). She was advised not to receive the second dose of the vaccine in view of the adverse event.

Postapproval, rare but serious adverse events including vaccineinduced thrombosis and thrombocytopenia, and myocarditis have been reported with adenoviral vectored and messenger RNA-based vaccines. [2] [3] [4] The inactivated vaccines in general have displayed a favorable safety profile in controlled settings. 1 In rare circumstances, however, cardiac, and new-onset musculoskeletal phenomena have been reported. 5 The patient in the current case had not been diagnosed as having RA in the past, although on leading questioning, a history of intermittent mild pain in bilateral knee joints was obtained.

The characteristic severe pain and tenderness in both small and large joints in a symmetric distribution and development of rheumatoid nodules were observed post the BBV152 vaccine. The associated hypereosinophilia was refractory to steroid therapy. Though the patient had elevated brain natriuretic peptide levels, there were no symptoms or signs of cardiac involvement. However, subclinical myocarditis cannot be ruled out. Since there was a delay in the patient being referred to our center, the possibility of a myocarditis event resolving by that time also 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 have a two times higher odds of development of adverse events following immunization. 6 

The top row mentions the timeline of vaccination, the onset of symptoms, the first referral to our center, and the onset of rheumatoid arthritis symptoms. Some investigations were performed over a range of days and have been mentioned as such. Investigation results of interest are marked in bold.

Measuring units and standard reference values from the concerned lab are mentioned in brackets beside each investigation.

Other parameters (platelet count, mean cell volume, random blood glucose, routine microscopy and culture of urine, and serum levels of urea, creatinine, sodium, potassium, uric acid, alanine aminotransferase, aspartate aminotransferase, total protein, albumin, total and direct bilirubin, alkaline phosphatase, calcium, phosphate) were within normal limits when measured at different time points 

The authors declare no conflicts of interest

No human experimentation was performed. All procedures were performed following the Declaration of Helsinki and its modifications.

Written informed consent was taken from the patient's legal guardian for publication of the case. 

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