Self-Reported Delayed Adverse Events and Flare Following COVID-19 Vaccination Among Patients With Autoimmune Rheumatic Disease (AIRD) in Malaysia: Results From the COVAD-2 Study

Int J Rheum Dis. 2025 Jan;28(1):e70043. doi: 10.1111/1756-185X.70043.

Abstract

Objectives: To determine the prevalence of self-reported delayed adverse events (DAEs), major AEs, and flares following COVID-19 vaccinations among patients with autoimmune rheumatic diseases (AIRDs) in Malaysia.

Methodology: An electronically validated survey from the COVID-19 vaccination in autoimmune diseases (COVAD) study group was distributed in July 2021 to patients with autoimmune diseases and healthy controls (HCs). The survey collected data on DAEs (any AE that persisted or occurred after 7 days of vaccination), any early or delayed major adverse events (MAEs), and flares following COVID-19 vaccination. Generalized estimating equation (GEE) models were performed to determine the factors associated with repeated events of DAEs, MAEs, and flares.

Results: A total of 556 vaccines were administered to 204 subjects (150 AIRDs and 54 HCs), with 72.1% completing 3 doses. In multivariate GEE analysis, there was a greater frequency of minor DAEs among AIRDs versus HCs (OR 5.65, p = 0.052). The occurrence of MAEs was higher in AIRDs versus HCs (4.9% vs. 1.3%, p = 0.052), but it was no longer significant in the GEE model. In the AIRDs group, the BNT162b2 vaccine increased the risk for minor DAEs (OR4.68, p = 0.02) while patients with autoimmune multimorbidity showed a greater risk for MAEs (OR 8.25, p = 0.007). The rate of flare was 10.6% and multivariate GEE analysis revealed that The rate of flare was 10.6% and multivariate GEE analysis revealed that systemic lupus erythematosus (SLE) (OR0.31, p = 0.03) and hydroxychloroquine (HCQ) (OR 0.16, p < 0.001) were protective against flare.

Conclusion: The rates of minor DAEs, major AEs, and flares were comparable with other reported studies. Different types of vaccines, underlying AIRDs, and treatments may influence the symptoms of AEs and flares postvaccination against COVID-19.

Keywords: COVID‐19 vaccine; autoimmunity; flares; quality of life.

MeSH terms

  • Adult
  • Aged
  • Autoimmune Diseases* / chemically induced
  • Autoimmune Diseases* / epidemiology
  • BNT162 Vaccine / adverse effects
  • COVID-19 Vaccines* / adverse effects
  • COVID-19* / epidemiology
  • COVID-19* / prevention & control
  • Case-Control Studies
  • Female
  • Humans
  • Malaysia / epidemiology
  • Male
  • Middle Aged
  • Rheumatic Diseases* / drug therapy
  • Rheumatic Diseases* / epidemiology
  • Rheumatic Diseases* / immunology
  • Risk Factors
  • SARS-CoV-2 / immunology
  • Self Report*
  • Symptom Flare Up
  • Time Factors
  • Vaccination / adverse effects

Substances

  • COVID-19 Vaccines
  • BNT162 Vaccine