Humoral and cellular response to COVID-19 vaccination in patients with autoimmune inflammatory rheumatic diseases under real-life conditions

Abstract

Objectives: Successful vaccination is key to overcoming the COVID-19 pandemic. Immunosuppressive medication is known to potentially compromise vaccination responses, and expansion of our knowledge on vaccination efficacy in patients with autoimmune inflammatory rheumatic diseases (AIIRD) is therefore of utmost importance.

Methods: We conducted a single-centre observational study and evaluated the efficacy of approved COVID-19 vaccines in 303 adult AIIRD patients. Serum levels of IgG antibodies against the S1 subunit of SARS-CoV-2 spike proteins (anti-S IgG) were measured at least two weeks after vaccination. In a subgroup of patients without humoral response, T-cell responses were determined using an interferon-γ gamma release assay.

Results: Overall seropositivity rate was 78.5% and was significantly lower in patients under immunosuppressive therapy (75.7 vs 93.2%, P = 0.009). No difference regarding the vaccination type was observed. Glucocorticoids, mycophenolate-mofetil, TNF inhibitors, tocilizumab, abatacept and rituximab were all associated with non-response after proper vaccination. The risk was highest under RTX therapy (OR 0.004, 95% CI 0.001, 0.023, P < 0.0001). A strong negative correlation was observed between time since vaccination with an mRNA vaccine and anti-S antibody levels (r=-0.6149, P < 0.0001). In patients without humoral response, a T-cell response was found in 50%.

Conclusions: COVID-19 vaccination in patients with AIIRD is effective using any approved vaccine. Humoral response might be impaired depending on the individual immunosuppressive medication. The risk of non-response is highest under rituximab therapy. Anti-S IgG antibody levels wane over time after mRNA vaccination. Importantly, 50% of humoral non-responders showed a T-cellular response, suggesting T-cell-mediated protection to a certain extent.

Keywords: COVID-19; cellular T-cell response; humoral response; immunosuppression; rheumatic diseases; vaccination.

Fig. 1

Comparison of IgG antibodies against the spike protein of SARS-CoV-2 (anti-S IgG) (A) Patients >60 vs <60 years, (B) Patients with and without DMARD therapy. Shown are individual values, median and interquartile range. The dotted line represents the seropositivity cut-off (7.1 BAU/ml).

Fig. 2

Odds ratios (OR) for seroconversion after COVID-19 vaccination as determined by multiple logistic regression ABA: abatacept; BEL: belimumab; GC: glucocorticoids; JAKi: JAK inhibitor; RTX: rituximab; TNFi: TNF inhibitor; TOZ: tocilizumab.

Fig. 3

Difference of anti-S IgG titre and antibody time course depending on the used vaccine (A) Anti-S IgG titre comparison after vaccination with either mRNA or vector vaccine. Shown are individual values, median and interquartile range. The dotted line represents the seropositivity cut-off (7.1 BAU/ml). (B) Relationship between anti-S IgG titre and time after vaccination with an mRNA-based vaccine. The shaded area represents the 95% CI. mRNA: messenger ribonucleic acid^{. ***}P<0.001.

Fig. 4

Comparison of ELIspot count between patients with detectable and depleted B cells Shown are individual values, mean and standard error of the mean.