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| LETTER TO EDITOR |
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| Ahead of print publication |
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New-Onset rheumatoid arthritis following ChAdOx1 nCoV-19 vaccine administration
Bhupen Barman1, Debashis Priyadarshan Sahoo1, Alvin Khangembam1, Muhammad Jamil1, Pranav Ish2
1 Department of General Medicine, North Eastern Indira Gandhi Regional Institute of Health and Medical Sciences, Shillong, Meghalaya
2 Department of Pulmonary, Critical Care and Sleep Medicine, Vardhman Mahavir Medical College and Safdarjung Hospital, New Delhi, India
| Date of Submission | 14-Mar-2022 |
| Date of Acceptance | 11-May-2022 |
| Date of Web Publication | 13-Jul-2022 |
Correspondence Address:
Bhupen Barman,
Department of General Medicine, North Eastern Indira Gandhi Regional Institute of Health and Medical Sciences, Mawdiangdiang, Shillong - 793 018, Meghalaya
Meghalaya
 Source of Support: None, Conflict of Interest: None DOI: 10.4103/injr.injr_51_22
| Introduction | |  |
COVID-19 caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a global health challenge with varied presentations. A number of vaccines including inactivated vaccines, protein subunit vaccines, viral vector vaccines, and nucleic acid-based vaccines have been developed across the globe for preventing the disease spread and severity.[1] Almost all these vaccines have adverse effects ranging from local site pain to systemic side effects such as fever, rash, and joint pain.[2] Viral or vaccine-induced autoimmunity is explained by homology between viral and human proteins.[3] Hence, exposure to COVID-19 or its spike proteins can lead to pathogenic priming leading to autoimmunity. Many cases of autoimmune diseases such as Kawasaki disease, antiphospholipid antibody syndrome, immune thrombocytopenic purpura, Guillain–Barré syndrome, autoimmune hemolytic anemia, and subacute thyroiditis have been reported after COVID-19 vaccination.[4] Rheumatoid arthritis (RA) is the most common autoimmune inflammatory polyarthritis in adults, and relapse of RA has also been reported postvaccination.[5],[6] Here, we report a case of development of new-onset RA in a 38-year-old female after taking the first dose of viral vector vaccine (ChAdOx1 nCoV-19).
| Case Report | | |
A 38-year-old female who was otherwise healthy developed acute severe bilateral symmetrical polyarthritis after the first dose of ChAdOx1 nCoV-19 vaccination. The patient had no known exposure to SARS-CoV-2 infection and had tested negative by polymerase chain reaction during routine screening at work. She received the first dose of ChAdOx1 nCoV-19 vaccine following which she developed mild fever and giddiness for which she took tablet acetaminophen. After 5 days of receiving vaccination, she developed joint pain mostly involving small joints including bilateral wrist joints. Gradually, she experienced significant pain and swelling in the bilateral wrists and metacarpophalangeal and proximal interphalangeal joints. They were associated with morning stiffness lasting more than 30 min, easy fatigability, and generalized body ache. She never had any history of joint pain in the past and did not have any known family history of any autoimmune disease. On examination, she was afebrile and hemodynamically stable. Radiographic findings of the hand joints were normal. She had a poor response to naproxen, and her investigations revealed hemoglobin of 11.6 gm/dl (reference range, 13.3–16.2), severe lymphopenia, high erythrocyte sedimentation rate (ESR) of 60 mm (reference range, 0–20 mm/1 h), high C-reactive protein level of 56.8 mg/dl (reference range, <10 mg/dl), a high ferritin level of 456 ng/ml (reference range, 29–248), with normal renal and liver function test and positive rheumatoid factor at a concentration of 155 IU/ml and anti-cyclic citrullinated peptide antibody with a serum level of >340 U/ml. Her rheumatology assessment revealed a high Disease Activity Score in 28 joints (DAS-28) of 5.67 (the tender joint count [TJC] was 8, the swollen joint count [SJC] was 5, patient global health [PGH] was 60 mm, and ESR was 42 mm/h). She was started on prednisolone 10 mg once daily, methotrexate 10 once a week, folic acid 5 my once a week (not in the day of methotrexate), hydroxychloroquine 200 mg twice daily, and sulfasalazine 500 mg twice daily. During the follow-up after 2 months following starting of medication, she was in partial remission from RA with a low DAS-28 score of 3.93(TJC – 3, SJC – 2, PGH – 20 mm, and ESR – 26 mm/h).
| Discussion | | |
Dysregulation of immune system and breakdown of self-tolerance are the main immunological events in RA. Self-reactive T-cells might rise in RA from abnormal thymic selection or intrinsic defects, which lower the threshold of T-cell activation. Cluster of differentiation 4 receptors on T-cells bind to major histocompatibility complex II, activating T-cells. Activated T-cells stimulate macrophages and fibroblast-like synoviocytes to generate pro-inflammatory mediators and proteases causing synovial inflammatory responses, destroying the cartilages and bones. Th1 cells mainly produce interferon-gamma, tumor necrosis factor (TNF)-α, and lymphotoxin-β, whereas Th2 (T-helper) cells produce interleukin-4 (IL-4), IL-5, IL-6, IL-10, and IL-13.[7] In COVID-19 infection, there is activation of innate immunity and production of pro-inflammatory molecules such as IL-1, IL-6, and TNF-α.[8] This mechanism is similar to RA disease development and progression. Certain components of vaccines like pathogenic antigens may induce immune activation and autoimmunity.[9] ChAdOx1 nCoV-19 vaccine is a viral vector vaccine, in which SARS-CoV-2 spike protein is carried by replication-deficient chimpanzee adenovirus vector.[10] It is effective against alpha, beta, and delta variants, by boosting T-cell immunity.[10] Hence, this process may trigger the immune system toward development of RA or its exacerbation. However, further investigation is needed to establish the relation between RA, COVID-19, and COVID-19 vaccination. Researchers across the globe are currently doing analysis on long-term safety and efficacy of COVID-19 vaccination in patients with autoimmune rheumatic diseases.[11] It is also possible that the timing of flare of the disease incidentally coincided with the timing of vaccination.
Similar reports of vaccine association with RA symptom or immune flare have been reported as early as five decades with tetanus, typhoid, paratyphoid, mumps, diphtheria, polio, and smallpox vaccination.[12] However, these reports have concluded that it may be a chance association, a distinct form of arthritis, or a trigger for RA requiring large-scale studies.[13]
Autoimmune/inflammatory syndrome induced by adjuvants is also an increasingly investigated entity.[14] Besides, postvaccination autoimmune phenomenon can be precipitated by multiple factors including the viral agent or the adjuvant.
| Conclusion | | |
Here, we report probably the first case of new-onset RA after COVID-19 vaccination. Pathophysiology of new-onset RA in relation to COVID-19 vaccination needs further research and evaluation. The risk–benefit ratio of COVID-19 vaccination in the current pandemic clearly favors vaccination[15] as it decreases the risk of infection, the severity, and the transmission. However, a high index of suspicion for the same and detailed evaluation for any autoimmune symptom postvaccination must always be carried out.
Declaration of patient consent
The authors certify that they have obtained all appropriate patient consent forms. In the form the patient (s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.
Financial support and sponsorship
Nil.
Conflicts of interest
There are no conflicts of interest.
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