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Autoimmune disorders reported following COVID-19 vaccination: A disproportionality analysis using the WHO database

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European Journal of Clinical Pharmacology Aims and scope Submit manuscript

Abstract

Purpose

Owing to adverse event following immunization (AEFI) related to autoimmune disorders and coronavirus disease 2019 (COVID-19) vaccines sharing common biological mechanisms, identifying the risk of AEFIs associated with COVID-19 vaccines remains a critical unmet need. We aimed to assess the potential safety signals for 16 AEFIs and explore co-reported adverse events (AEs) and drugs using the global database of the World Health Organization, VigiBase.

Methods

We assessed the occurrence of 16 AEFIs following COVID-19 vaccination through the Standardized MedDRA Queries group “Immune-mediated/Autoimmune Disorders” from MedDRA and performed a disproportionality analysis using reporting odds ratio (ROR) and information component (IC) with 95% confidence intervals (CIs).

Results

We identified 25,219 events associated with COVID-19 vaccines in VigiBase. Although rare, we detected four potential safety signals related to autoimmune disorders following COVID-19 vaccination, including ankylosing spondylitis or psoriatic arthritis (ROR 1.86; 95% CI 1.53–2.27), inflammatory bowel disease (ROR 1.77; 95% CI 1.60–1.96), polymyalgia rheumatica (ROR 1.42; 95% CI 1.30–1.55), and thyroiditis (ROR 1.40; 95% CI 1.30–1.50), with positive IC025 values. The top co-reported AEs were musculoskeletal disorders, and immunosuppressants were the most representative co-reported drugs.

Conclusion

In addressing the imperative to comprehend AEFI related to autoimmune disorders following COVID-19 vaccination, our study identified four potential safety signals. Thus, our research underscores the importance of proactive safety monitoring for the identification of the four AEFIs following COVID-19 vaccination, considering the associated advantages.

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Availability of data and materials

The data that support the findings of this study are available from Uppsala Monitoring Centre, but restrictions apply to the availability of these data, which were used under license for the current study, and so are not publicly available. Data are however available from the authors upon reasonable request and with permission of Uppsala Monitoring Centre.

References

  1. Michot JM et al (2019) Haematological immune-related adverse events with immune checkpoint inhibitors, how to manage? Eur J Cancer 122:72–90

    Article  CAS  PubMed  Google Scholar 

  2. Garrido I et al (2021) Autoimmune hepatitis after COVID-19 vaccine - more than a coincidence. J Autoimmun 125:102741

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Grana C et al (2022) Efficacy and safety of COVID-19 vaccines. Cochrane Database Syst Rev 12(12):CD015477

  4. Pavord S et al (2021) Clinical features of vaccine-induced immune thrombocytopenia and thrombosis. N Engl J Med 385(18):1680–1689

    Article  CAS  PubMed  Google Scholar 

  5. Pang E et al (2022) Cerebral arterial and venous thrombosis due to COVID-19 vaccine-induced immune thrombotic thrombocytopenia. BMJ Case Rep 15(1)

  6. Rizk JG et al (2021) Clinical characteristics and pharmacological management of COVID-19 vaccine-induced immune thrombotic thrombocytopenia with cerebral venous sinus thrombosis: a review. JAMA Cardiol 6(12):1451–1460

    Article  MathSciNet  PubMed  Google Scholar 

  7. Ishay Y et al (2021) Autoimmune phenomena following SARS-CoV-2 vaccination. Int Immunopharmacol 99

  8. Safary A et al (2022) Autoimmune inflammatory rheumatic diseases post-COVID-19 vaccination. Int Immunopharmacol 110

  9. Bril F et al (2021) Autoimmune hepatitis developing after coronavirus disease 2019 (COVID-19) vaccine: causality or casualty? J Hepatol 75(1):222–224

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Hippisley-Cox J et al (2021) Risk of thrombocytopenia and thromboembolism after COVID-19 vaccination and SARS-CoV-2 positive testing: self-controlled case series study. BMJ 374:n1931

    Article  PubMed  Google Scholar 

  11. Ostrowski SR et al (2021) Inflammation and platelet activation after COVID-19 vaccines - possible mechanisms behind vaccine-induced immune thrombocytopenia and thrombosis. Front Immunol 12:779453. https://doi.org/10.3389/fimmu.2021.779453

  12. Abara WE et al (2023) Reports of Guillain-Barré syndrome after COVID-19 vaccination in the United States. JAMA Netw Open 6(2):e2253845. https://doi.org/10.1001/jamanetworkopen.2022.53845

  13. Hanson KE et al (2022) Incidence of Guillain-Barré syndrome after COVID-19 vaccination in the vaccine safety datalink. JAMA Netw Open 5(4):e228879. https://doi.org/10.1001/jamanetworkopen.2022.8879

  14. Oliver SE et al (2022) Use of the Janssen (Johnson & Johnson) COVID-19 vaccine: updated interim recommendations from the Advisory Committee on Immunization Practices - United States, December 2021. MMWR Morb Mortal Wkly Rep 71(3):90–95

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Noseda R et al (2021) Adverse event reporting with immune checkpoint inhibitors in older patients: age subgroup disproportionality analysis in VigiBase. Cancers (Basel) 13(5)

  16. Sen, Parikshit et al (2022) COVID-19 vaccination-related adverse events among autoimmune disease patients: results from the COVAD study. Rheumatology (Oxford, England)62(1):65–76. https://doi.org/10.1093/rheumatology/keac305

  17. Yoon, Dongwon et al (2021) Association between human papillomavirus vaccination and serious adverse events in South Korean adolescent girls: nationwide cohort study. BMJ (Clinical research ed.) 372:m4931. https://doi.org/10.1136/bmj.m4931

  18. Standardised MedDRA Queries | MedDRA. https://www.meddra.org/standardised-meddra-queries

  19. van Puijenbroek EP et al (2002) A comparison of measures of disproportionality for signal detection in spontaneous reporting systems for adverse drug reactions. Pharmacoepidemiol Drug Saf 11(1):3–10

    Article  PubMed  Google Scholar 

  20. Lumini A, Nanni L (2018) Convolutional neural networks for ATC classification. Curr Pharm Des 24(34):4007–4012

    Article  CAS  PubMed  Google Scholar 

  21. Patone M et al (2021) Neurological complications after first dose of COVID-19 vaccines and SARS-CoV-2 infection. Nat Med 27(12):2144-+

  22. Xing E et al (2022) Sex bias and autoimmune diseases. J Invest Dermatol 142(3):857–866. https://doi.org/10.1016/j.jid.2021.06.008

  23. Sellner J et al (2011) The increasing incidence and prevalence of female multiple sclerosis--a critical analysis of potential environmental factors. Autoimmun Rev 10(8):495–502. https://doi.org/10.1016/j.autrev.2011.02.006

  24. Li X et al (2022) Lack of inflammatory bowel disease flare-up following two-dose BNT162b2 vaccine: a population-based cohort study. Gut 71(12):2608–2611

    Article  CAS  PubMed  Google Scholar 

  25. Weaver KN et al (2022) Impact of SARS-CoV-2 vaccination on inflammatory bowel disease activity and development of vaccine-related adverse events: results from PREVENT-COVID. Inflamm Bowel Dis 28(10):14971505. https://doi.org/10.1093/ibd/izab302

  26. Masuta Y et al (2022) A case of ulcerative colitis relapse characterized by systemic type i interferon responses after COVID-19 vaccination. Inflamm Bowel Dis 28(8):e110-e111. https://doi.org/10.1093/ibd/izac031

  27. Mettler C et al (2022) Risk of giant cell arteritis and polymyalgia rheumatica following COVID-19 vaccination: a global pharmacovigilance study. Rheumatology (Oxford) 61(2):865–867

    Article  CAS  PubMed  Google Scholar 

  28. Rider LG et al (2022) Baseline factors associated with self-reported disease flares following COVID-19 vaccination among adults with systemic rheumatic disease: results from the COVID-19 global rheumatology alliance vaccine survey. Rheumatology (Oxford) 61(SI2):SI143-SI150

  29. McGonagle D, De Marco G, Bridgewood C (2021) Mechanisms of immunothrombosis in vaccine-induced thrombotic thrombocytopenia (VITT) compared to natural SARS-CoV-2 infection. J Autoimmun 121

  30. Teijaro JR, Farber DL (2021) COVID-19 vaccines: modes of immune activation and future challenges. Nat Rev Immunol 21(4):195–197

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Reikine S, Nguyen JB, Modis Y (2014) Pattern recognition and signaling mechanisms of RIG-I and MDA5. Front Immunol 5

  32. Frontera JA et al (2022) Neurological events reported after COVID-19 vaccines: an analysis of VAERS. Ann Neurol 91(6):756–771

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Weschawalit S et al (2023) Cutaneous adverse events after COVID-19 vaccination. Clin Cosmet Investig Dermatol 16:1473–1484. https://doi.org/10.2147/CCID.S410690

  34. Ursini F et al (2022) Spectrum of short-term inflammatory musculoskeletal manifestations after COVID-19 vaccine administration: a report of 66 cases. Ann Rheum Dis 81(3):440–441

    Article  CAS  PubMed  Google Scholar 

  35. Ritchlin CT, Colbert RA, Gladman DD (2017) Psoriatic arthritis. N Engl J Med 376(10):957–970

    Article  PubMed  Google Scholar 

  36. Polack FP et al (2020) Safety and efficacy of the BNT162b2 mRNA COVID-19 vaccine. N Engl J Med 383(27):2603–2615

    Article  CAS  PubMed  Google Scholar 

  37. Ozonoff Al et al (2021) Bell’s palsy and SARS-CoV-2 vaccines. The Lancet. Infect Dis 21(4):450–452. https://doi.org/10.1016/S1473-3099(21)00076-1

  38. Arnold J, Winthrop K, Emery P (2021) COVID-19 vaccination and antirheumatic therapy. Rheumatology (Oxford) 60(8):3496–3502

    Article  CAS  PubMed  Google Scholar 

  39. Mohseni Afshar Z et al (2022) Coronavirus disease 2019 (COVID-19) vaccination recommendations in special populations and patients with existing comorbidities. Rev Med Virol 32(3):e2309

    Article  CAS  PubMed  Google Scholar 

  40. Rosenthal S, Chen R (1995) The reporting sensitivities of two passive surveillance systems for vaccine adverse events. Am J Public Health 85:1706–1709

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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Funding

This research was supported by the Ministry of Food and Drug Safety of South Korea (grant numbers 21153MFDS607 and 22183MFDS433). The funders of the study had no role in study design, data collection, data analysis, data interpretation, or writing of the manuscript. The corresponding author had full access to all the data in the study and had final responsibility for the decision to submit for publication.

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Authors and Affiliations

  1. Department of Biohealth Regulatory Science, Sungkyunkwan University, Suwon, South Korea

    Seohyun Kim & Ju-Young Shin

  2. School of Pharmacy, Sungkyunkwan University, 2066 Seobu-ro, Jangan-gu, Suwon-si, Gyeonggi-do 16419, South Korea

    Sungho Bea & Ju-Young Shin

  3. Department of Preventive Medicine, Korea University College of Medicine, Seoul, South Korea

    Seung-Ah Choe

  4. Department of Health Convergence, College of Science & Industry Convergence, Ewha Womans University, Seoul, Korea

    Nam-Kyong Choi

  5. Department of Clinical Research Design & Evaluation, Samsung Advanced Institute for Health Sciences & Technology, Sungkyunkwan University, Seoul, South Korea

    Ju-Young Shin

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  1. Seohyun Kim
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Contributions

S.K. designed the study, collected the data, performed the statistical analyses, interpreted the data, and wrote the manuscript. S.B. designed the study, interpreted the data, and contributed to the writing of the manuscript. S.A. and N.K. critically interpreted data and manuscript. J.Y.S. designed the study, supervised the statistical analyses and interpretation of the data, and critically revised the manuscript. J.Y.S., the guarantor of the study, accepts full responsibility for the results of this study, has access to the data, and controls the decision to publish. The corresponding author attests that all listed authors meet the authorship criteria and that no others meeting the criteria have been submitted.

Corresponding author

Correspondence to Ju-Young Shin.

Ethics declarations

Ethics approval and consent to participate

The institutional review board of Sungkyunkwan University approved the study (IRB No. SKKU 2023-02-038); the board waived the requirement for obtaining informed consent as this study used anonymized administrative data.

Conflict of interest

The authors declare no competing interests.

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Seohyun Kim and Sungho Bea contributed equally to this work.

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Kim, S., Bea, S., Choe, SA. et al. Autoimmune disorders reported following COVID-19 vaccination: A disproportionality analysis using the WHO database. Eur J Clin Pharmacol 80, 445–453 (2024). https://doi.org/10.1007/s00228-023-03618-w

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  • DOI: https://doi.org/10.1007/s00228-023-03618-w

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