Serological Response to BNT162b2 Anti-SARS-CoV-2 Vaccination in Patients with Inflammatory Rheumatic Diseases: Results From the RHEUVAX Cohort

Abstract

Objective: In the light of the current COVID-19 epidemic and the availability of effective vaccines, this study aims to identify factors associated with non-response to anti-SARS-CoV-2 vaccines as immunological alteration associated with immune rheumatic diseases (IRD) and immunosuppressive medications may impair the response to vaccination.

Methods: Volunteers in the health profession community with IRD, age, and sex-matched controls (CTRL) who underwent vaccination with two doses of BNT162b2 were recruited for this study. Anti-Trimeric Spike protein antibodies were assayed eight ± one weeks after the second vaccine dose. Univariate and logistic regression analyses were performed to identify factors independently associated with non-response and low antibody titers.

Results: Samples were obtained from 237 IRD patients (m/f 73/164, mean age 57, CI 95% [56-59]): 4 autoinflammatory diseases (AI), 62 connective tissue diseases (CTD), 86 rheumatoid arthritis (RA), 71 spondylarthritis (SpA) and 14 vasculitis (Vsc). 232 CTRL were recruited (m/f 71/161, mean age 57, CI 95% [56-58]). Globally, IRD had a lower seroconversion rate (88.6% vs 99.6%, CI 95% OR [1.61-5.73], p<0.001) and lower antibody titer compared to controls (median (IQR) 403 (131.5-1012) versus 1160 (702.5-1675), p<0.001). After logistic regression, age, corticosteroid (CCS), Abatacept and Mycophenolate Mofetil (MMF) use were associated with non-response. Lower antibody titer was associated with the use of MMF, ABA, CCS, Rituximab, tumor necrosis factor inhibitor, JAK inhibitors, and higher age.

Conclusion: The response to anti-SARS-CoV-2 vaccines is often impaired in IRD patients under treatment and may pose them at higher risk of severe COVID-19. Specific vaccination protocols are desirable for these patients.

Keywords: COVID-19; arthritis; autoimmunity; connective tissue disease (CTD); rheumatic and muscoluskeletal disease; vaccines.

Figure 1

Seroconversion rates after BNT162B2 vaccine in IRD and controls: Mosaic plots represent the percentage of serological response and non-response in controls (CTRL) and patients (IRD); bar size is proportional with the sample size (n) of the group. (A) stratification according to sex and age (> vs < the median); (B) percentage of response across different IRD diagnoses; (C) response in patients treated with csDMARDs; (D) response in patients treated with bDMARDs or tsDMARDs; In (E–G) stratification performed according to RTX treatment in the last 12 months, CCS use and past Sars-Cov-2 infection, respectively. In (H) forest plot showing factors associated with of seroconversion identified by binary stepwise logistic regression displayed as 95% CI of Ln(Odds Radio) and p-value. Full analysis results and p-values are reported in Supplementary Table 1 . *: statistically significant vs control population; #: statistically significant vs not taking csDMARDs or bDMARDs/tsDMARDs; */# = p < 0.05.

Figure 2

Antibody titers after BNT162B2 vaccine in IRD and controls:Box and whiskers plot with individual data point anti-Sars-CoV-2 antibody tier expressed in BAU/mL, the box represents the IQR, line the median and hinges extend from the minimum to maximum value (A–G). In (A) comparison of titer between control (CTRL) and patients (IRD). In (B, C) titer after stratification for sex and age (> vs < the median), respectively. Levels of anti-Sars-Cov2 antibodies in the different patient’s groups are reported in (D). In (E) antibody levels after stratification for CCS use, past COVID19 and Rituximab treatment in the last 12 months. Antibody levels are compared across different csDMARDs (F) and bDMARDs/tsDMARDs (G) use. In (H) forest plot showing factors associated with seroconversion identified by linear stepwise regression displayed as 95% CI of B and p-value. *: statistically significant vs control population; #: statistically significant vs not taking csDMARDs or bDMARDs/tsDMARDs; **/## = p < 0.01; ***/### = p < 0.001. ns, not significant.