The T-cell response to SARS-CoV- 2 vaccination persists beyond six months in rheumatoid arthritis patients treated with rituximab

Abstract

Background: The spike protein-specific humoral response observed after SARS-CoV- 2 vaccination is decreased in rheumatoid arthritis (RA) patients treated with rituximab (RTX). However, when analyzed immediately after vaccination, the spike-specific T-cell immune response appears to be preserved. The possible persistence of specific T cells over the long term is underexplored and could be a useful decision-making tool for deciding when to perform revaccination. This study aimed to assess the persistence of T-cell-mediated immunity after the last SARS-CoV- 2 vaccination or infection (named “SARS-CoV- 2 boost” in this study) in RA patients treated with RTX. Clinical and biological parameters that can influence this immune system were also explored. Methods: Our observational study cohort included 51 RA patients treated with RTX and 24 RA patients treated with other disease-modifying antirheumatic drugs (DMARDs) who had received at least one dose of the SARS-CoV- 2 mRNA vaccine. The T-cell immune response was assessed by flow cytometry, which focused on antigen-specific T-cell characterization between 3 and 18 months after the last SARS-CoV- 2 boost. T-cell activation was assessed by measuring CD69, CD154, CD137 and CD107a surface expression. Results: As expected, even if a lower mean antibody titer was measured in RA patients receiving RTX (RA RTX) than in RA patients treated with therapies other than RTX (p = 0.034), all patients exhibited CD4 + and CD8 + T-cell spike protein-specific responses, with an even greater spike-specific CD8 + T-cell response in RA RTX patients (p < 0.001). The main finding of our study was that the T-cell response remarkably persisted up to 18 months after the last SARS-CoV- 2 boost and no difference was found in COVID- 19 severity between RTX- and non-RTX-treated patients (p = 0.770). Conclusions: Even if RTX treatment prevented the SARS-CoV- 2 vaccine-dependent antibody response in RA patients, a strong spike protein-specific T-cell-mediated response that persisted for up to 18 months after the last SARS-CoV- 2 boost was found in RA RTX patients. With respect to personalized medicine, analyzing the spike protein-specific T-cell response might be a valuable strategy for deciding when revaccination is necessary.