Immune features revealed by single‐cell RNA and single‐cell TCR/BCR sequencing in patients with rheumatoid arthritis receiving COVID‐19 booster vaccination

Abstract Coronavirus disease 2019 (COVID‐19), caused by SARS‐CoV‐2, have profoundly affected human health. Booster COVID‐19 vaccines have demonstrated significant efficacy in reducing infection and severe cases. However, the effects of booster COVID‐19 vaccines on key immune cell subsets and their responses in rheumatoid arthritis (RA) are not well understood. By using single‐cell RNA sequencing (scRNA‐seq) combined with scTCR/BCR‐seq analysis, a total of 8 major and 27 minor cell clusters were identified from paired peripheral blood mononuclear cells (PBMCs) which were collected 1 week before and 4 weeks after booster vaccination in stable RA patients. Booster vaccination only had limited impact on the composition and proportions of PBMCs cell clusters. CD8+ cytotoxic T cells (CD8+T_CTL) showed a trend toward an increase after vaccination, while naive B cells and conventional dendritic cells (cDCs) showed a trend toward a decrease. Transcriptomic changes were observed after booster vaccination, primarily involving T/B cell receptor signaling pathways, phagosome, antigen processing and presenting, and viral myocarditis pathways. Interferon (IFN) and pro‐inflammatory response gene sets were slightly upregulated across most major cell subpopulations in COVID‐19 booster‐vaccinated RA individuals. Plasma neutralizing antibody titers significantly increased after booster COVID‐19 vaccination ( p = 0.037). Single‐cell TCR/BCR analysis revealed increased B cell clone expansion and repertoire diversity postvaccination, with no consistent alterations in T cells. Several clonotypes of BCRs and TCRs were identified to be significantly over‐represented after vaccination, such as IGHV3‐15 and TRBV28. Our study provided a comprehensive single‐cell atlas of the peripheral immune response and TCR/BCR immune repertoire profiles to inactivated SARS‐CoV‐2 booster vaccination in RA patients, which helps us to understand vaccine‐induced immune responses better.