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

Abstract

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. 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. 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). 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.