Background: COVID-19 vaccines are associated with various mild to moderate side effects. Post COVID-19 vaccine induced autoimmune rheumatic diseases (ARDs) are one of the serious side effects attributed to COVID-19 vaccines.

Objectives: Despite the significant benefits of the COVID-19 vaccine in improving global health and contributing to herd immunity, they are associated with various mild to moderate side effects including myalgia, injection site pain, arthralgia, lymphadenopathy, fatigue, headache, fever, swelling, nausea, vomiting, tingling, itching and chills. Given that there were many reports of autoimmune disorders following vaccination against tetanus, rubella, hepatitis B, and influenza, concerns were quickly raised that COVID-19 vaccines might cause autoimmune rheumatic diseases (ARDs). But considering that the majority of the world’s population has been vaccinated against COVID-19, the occurrence of rheumatism in a few cases may be a random phenomenon and there may not be a causal relationship between vaccination against COVID-19 and the occurrence of ARD. Therefore, we conducted a systematic review to summarize data on reports of ARD after COVID-19 vaccination.

Methods: The literature was searched from 2020 to September 2024. Inclusion criteria were meeting the classification criteria of one of the ARDs, the onset of ARDs symptoms at 1-30 after receiving the first, second, or third dose of COVID-19 vaccines, age ≥ 16 and no previous history of ARDs. Patients with identified ARD before vaccination, patients who experienced ARD symptoms after COVID-19 infection and patients who developed ARD after 30 days of receiving the vaccine were excluded.

Results: We identified 715 articles. After removing duplicates and screening studies through title and abstract, 226 reports were evaluated for eligibility and finally 181 reports were included in the study. After reviewing these reports, 372 cases were identified who developed ARD within 30 days after receiving the COVID-19 vaccine (Figure 1). Among reported patients, 234 (62.9%) were female. The mean age was 55.1±18.1 years. ARD was developed in median (interquartile range) of 7 (4, 14) days after vaccination. In 316 patients whose vaccine dose was reported, ARD occurred after the first dose in 160 cases (50.6%), after the second dose in 148 cases (46.8%) and after the third dose in 8 cases (2.5%). The most common group of ARDs reported were vasculitis, which occurred in 189 cases (50.8%). CTD and inflammatory arthritis were reported in 89 (23.9%) and 69 (18.5%) cases, respectively (Figure 2). The 5 most common post vaccine ARDs were AAV, UIPA, PMR/GCA, IIM and CSVV, which were reported in 54 (14.5%), 51 (13.7%), 47 (13.5%), 41 (11%), and 31 (8.3%) cases, respectively. Outcome was reported in 308 cases. Complete remission was obtained in 269 (87.3%) cases. Two patients died due to complications of ARD. In 366 patients, the type of vaccine was specified in the report, which is as follows: Pfizer in 203 (55.7%), AstraZeneca in 92 (25.1%), Moderna in 38 (10.4%), Sinopharm in 8 (2.2%), CoronaVac (Sinovac) in 6 (1.6%), Covishield in 4 (1.1%), Covaxin in 4 (1.1%), Janssen & Janssen in 4 (1.1%), COVIran Barekat in 4 (1.1%) and Sputnik in 3 (0.8%) cases. Based on the reported cases, 3 main vaccine groups, nucleic acid-based (mRNA), viral vector and whole virus, caused ARD in 245 (66.9%), 99 (27%) and 22 (6%) cases, respectively (Table 1, Figure 3). It should be noted that the vaccines used for public vaccination in the world by Dec 2024 are Pfizer in 4.6 billion (26.9%), AstraZeneca in 3 billion (17.5%), CoronaVac in 2.8 billion (16.4%), Covishield in 2.4 billion (14%), Sinopharm in 1.6 billion (9.3%), Moderna in 1.3 billion (7.4%), Jhonson & Johnson in 0.7 billion (4.1%), Covaxin in 0.4 billion (2.3%), Sputnik in 0.3 billion (1.6%) and COVIran Barekat in 0.1 billion (0.35%). Crosstabulation analysis showed that ARD was significantly more common in subjects who received Pfizer vaccine than in subjects who received other vaccines (odds ratio=3.25, confidence interval=1.82-5.82, P-value=0.001). There was no significant association between the type of vaccine and type of ARDs.

Figure 1.

The PRISMA flow chart of literature search for patients with ARDs post COVID-19 vaccination.

PRISMA: preferred reporting items for systematic reviews and meta-analyses.

ARDs: autoimmune rheumatic diseases

Figure 2.

A column chart showing the number of cases of post COVID-19 vaccination ARDs by vaccine category.

ARDs: autoimmune rheumatic diseases

Conclusion: This systematic review provides important insights into ARDs after COVID-19 vaccination and has significant clinical implications. Clinicians should be cautious and consider ARDs in the differential diagnosis of patients presenting with musculoskeletal or multisystem complaints after vaccination, especially nucleic acid-based vaccines.

REFERENCES: NIL.

Acknowledgements: We would like to express our thanks the Connective Tissue Diseases Research Center of Tabriz University of Medical Sciences for supporting this study.

Disclosure of Interests: None declared.

© The Authors 2025. This abstract is an open access article published in Annals of Rheumatic Diseases under the CC BY-NC-ND license ( http://creativecommons.org/licenses/by-nc-nd/4.0/ ). Neither EULAR nor the publisher make any representation as to the accuracy of the content. The authors are solely responsible for the content in their abstract including accuracy of the facts, statements, results, conclusion, citing resources etc.