MRNA COVID-19 vaccines weaker in patients with autoimmune systemic diseases

Patients with autoimmune systemic diseases (ASD) are less likely to produce an immune response following inoculation with mRNA vaccines against the coronavirus disease 2019 (COVID-19), according to a recent study.

“According to our data, a significantly higher percentage of patients failed to mount a response within 1–3 weeks after completion of the vaccination cycle when compared to controls, particularly for cryoglobulinaemic vasculitis (CV) or systemic vasculitis,” the researchers said, adding that COVID-19 vaccines nevertheless remained safe for these patients.

The current prospective, observational, multicentre study involved 478 unselected patients (mean age 59±15 years) with ASDs such as rheumatoid arthritis, systemic lupus erythematosus, CV, and other systemic vasculitis conditions. Serum levels of IgG-neutralizing antibodies (NAbs) were measured 3 weeks after the completion of vaccination to assess the immunogenicity of the mRNA shots. A parallel group of 502 vaccinated, general-population controls was also included.

After vaccination, ASD patients showed a median IgG-NAb titre of 286 BAU/mL, almost three times lower than that in controls (825 BAU/mL; p<0.0001). Disaggregating ASD patients according to specific diseases likewise showed significant suppression of titres relative to controls (p<0.05 for all). [J Autoimmun 2021;125:102744]

In turn, the percentage of vaccine nonresponders, defined as IgG-NAb levels below the threshold of detection, was significantly higher in ASD patients vs controls (13.2 percent vs 2.8 percent; p<0.001). The same remained true in every ASD subgroup.

Aside from ASDs, the researchers also found that ongoing medication affected vaccine response. For instance, glucocorticoids were significantly more common among patients who were negative vs positive for IgG-NAbs (60.3 percent vs 40.0 percent; p=0.002). Similarly, treatment with mycophenolate mofetil or rituximab was significantly more common among nonresponders (p<0.0001 for both).

Multivariate logistic regression analysis revealed that only treatment with rituximab was significantly and independently predictive of impaired vaccine immunogenicity (odds ratio [OR], 4.031, 95 percent confidence interval [CI], 1.454–11.105; p=0.007).

However, unadjusted analysis showed that existing ASD-related interstitial lung disease (OR, 2.106, 95 percent CI, 1.198–3.702; p=0.01), as well as treatment with glucocorticoids (OR, 2.27, 95 percent CI, 1.321–3.903; p=0.003) and mycophenolate mofetil (OR, 3.078, 95 percent CI, 1.701–5.567; p<0.0001), could also be important correlates of attenuated immune response.

While the mRNA COVID-19 vaccines elicited weaker responses in ASD patients, they nevertheless kept their favourable safety profiles. Side effects were commonly reported in participants, especially cases of headache and pain at injection site, though all were of mild severity and resolved with time.

“In our opinion, patients showing a suboptimal response should be prioritized for a booster-dose of vaccine, while the administration of a different type of vaccine could be attempted in nonresponder individuals,” the researchers said.