Does the status of micronutrients affect immune response to COVID-19 mRNA vaccination in rheumatoid arthritis patients?

Abstract

Introduction: Rheumatoid arthritis (RA) is a chronic autoimmune disease that primarily affects the joints. It is recommended to start disease-modifying anti-rheumatic drugs (DMARDs) as soon as RA diagnosis is confirmed. The role of zinc, copper, magnesium, and ceruloplasmin on vaccine-induced immunoglobulin G (IgG) responses remains uncertain, particularly in the context of RA patients receiving ongoing immunosuppressive treatments. This study aimed to explore the association between baseline levels of these trace elements and IgG responses in RA patients following the second dose of the coronavirus disease 2019 (COVID-19) mRNA vaccine, within a 12–16-week interval. It also examined how DMARD treatments and trace element status relate to vaccine-induced immune responses, by comparing to a healthy control group.

Methodology: An observational cross-sectional study was conducted including 79 RA patients and 47 healthy controls. Serum levels of zinc, copper, magnesium, ceruloplasmin, and IgG were measured.

Results: Significant differences in zinc, copper, and magnesium levels were observed between vaccinated and unvaccinated individuals within both patient and control groups (p < 0.05). However, there were no significant associations between IgG positivity and trace element levels within any group (p > 0.05). Similarly, IgG positivity was not significantly associated with biological or non-biological treatment intake (p = 0.439).

Conclusions: COVID-19 mRNA vaccines produced a broadly consistent humoral immune response across participants, regardless of zinc, copper, magnesium, and ceruloplasmin levels. There were no significant associations between trace element status, RA treatment, and long-term antibody durability; suggesting that humoral immunity may be maintained across different nutritional and therapeutic profiles.