BACKGROUNDThe effect of a preexisting comorbidity on the occurrence of adverse events after immunization (AEFIs) has been studied poorly. In this longitudinal cohort study, we assess the association between co-morbidities and the occurrence of AEFIs after COVID-19 vaccination. Also, we described the occurrence of flare-ups and their manifestation after COVID-19 vaccination in people with rheumatic diseases.RESEARCH DESIGN AND METHODSWe performed multivariable logistic regression to investigate the association between the occurrence of AEFIs and 10 common comorbidities using patient-reported data from people vaccinated with the AstraZeneca, Johnson&Johnson, Moderna, or Pfizer vaccine.RESULTSOccurrence of any AEFI, injection site reactions, headache, fatigue, and/or malaise was significantly associated with presence of comorbidities, including psychological disorders, musculoskeletal disorders, and endocrine disorders after the first and second doses (OR ranges 1.23-1.77). One participant with rheumatoid arthritis experienced a flare-up after receiving the first dose of the AstraZeneca vaccine.DISCUSSION/CONCLUSIONThe results showed that the odds of reporting an AEFI after COVID-19 vaccination is significantly higher in the presence of some comorbidities whilst flare-ups are uncommon after receiving COVID-19 vaccination in people with rheumatic disease. In-depth research is needed to validate our results and unravel the observed associations from a mechanistic perspective.