Biological and glucocorticoids treatment impair the medium-term immunogenicity to SARS-CoV-2 mRNA vaccines in autoimmune inflammatory rheumatic diseases

Abstract

Background: This study aims to assess the sustained immunological response to the SARS-CoV-2 vaccine in patients with autoimmune inflammatory rheumatic diseases (AIRD) undergoing different treatment regimens.

Methods: We conducted a prospective observational study involving 157 AIRD patients without prior COVID-19 infection. Treatment regimens included non-treatment or glucocorticoid-only (not-treated/GCs), non-biological drugs, biological therapy, and JAK inhibitors. All participants completed the two-dose vaccine schedule, and 110 of them received an additional booster dose. Serum samples were collected approximately 3-6 months after the second and third vaccine doses to measure antibodies against the Spike protein (antiS-AB) and neutralizing antibodies (nAB) targeting six SARS-CoV-2 variants.

Results: Following the third dose, all patients exhibited a significant increase in antiS-AB (FC = 15, p < 0.0001). Patients under biological therapy had lower titres compared to the non-biological (66% decrease, p = 0.038) and the not-treated/GCs group (62% decrease, p = 0.0132), with the latter persisting after the booster dose (86% decrease, p = 0.0027). GC use was associated with lower antiS-AB levels in the biological group (87% decrease, p = 0.0124), although not statistically significant after confounders adjustment. nABs showed the highest positivity rates for the wild-type strain before (50%) and after the booster dose (93%), while the Omicron variant exhibited the lowest rates (11% and 55%, respectively). All variants demonstrated similar positivity patterns and good concordance with antiS-AB (AUCs from 0.896 to 0.997).

Conclusions: The SARS-CoV-2 vaccine booster strategy effectively elicited a sustained antibody immune response in AIRD patients. However, patients under biological therapies exhibited a reduced response to the booster dose, particularly when combined with GCs.

Keywords: Autoimmune disease; COVID19; Immune response; Neutralizing antibodies.

Fig. 1

Anti-S protein antibodies titers by treatment groups before and after a third dose of mRNA-based SARS-CoV-2 vaccine. The circle-shaped dots show the levels of anti-S protein antibodies of the patients' baseline and follow-up samples. The diamond-shaped points and the adjacent segments display the adjusted group means of the titer values and their corresponding 95% confidence intervals, respectively. Dot colors indicate the patients’ disease condition. Adjusted means were derived from a mixed-effects linear model where sex, age, rheumatic condition, treatment type, use of glucocorticoids, type of vaccine, sample type (pre- or post-third dose) and time from previous dose where included as fixed effects, as well as the interaction between: sex and sample type; treatment and sample type; rheumatic condition and sample type; use of glucocorticoids and sample type; time from second and third vaccine dose and sample type; glucocorticoids use and treatment regimen; and glucorticoids use and rheumatic condition. Individual effects were included as random effects in this model. The y-axis is in log2-scale, while the value labels are displayed in the original scale of the titer values (BAU/ml). The horizontal dotted line indicates a value of 260 BAU/ml, which is typically used as a threshold to define a positive response to the vaccine. SLE Systemic Lupus Erythematosus, RA Rheumatoid Arthritis, B27-AS HLA-B27 positive Ankylosing Spondylitis, PSA Psoriatic Arthritis, GCA Giant Cell Arteritis, GCs Glucocorticoids; JAKi JAK inhibitors

Fig. 2

Quantification of neutralizing antibodies by treatment regimen before and after a third dose of mRNA-based SARS-CoV-2 vaccine for variants Wild type (A) and B.1.1.529 (Omicron) (B). The dots show the quantitative estimations of neutralizing antibodies abundance of the patients' baseline and follow-up samples. Dot colors indicate the patients' rheumatic condition. Horizontal dotted lines display the threshold for no detection of antibody (ND) and positivity. SLE Systemic Lupus Erythematosus, RA Rheumatoid Arthritis, B27-AS HLA-B27 positive Ankylosing Spondylitis, PSA Psoriatic Arthritis, GCA Giant Cell Arteritis, GCs Glucocorticoids; JAKi JAK inhibitors, nABs neutralizing antibodies