Dynamics of SARS-CoV-2 immunity after vaccination and breakthrough infection in rituximab-treated rheumatoid arthritis patients: a prospective cohort study.

Background: SARS-CoV-2 vaccination in rheumatoid arthritis (RA) patients treated with B cell-depleting drugs induced limited seroconversion but robust cellular response. We aimed to document specific T and B cell immunity in response to vaccine booster doses and breakthrough infection (BTI).
Methods: We included 76 RA patients treated with rituximab who received up to four SARS-CoV-2 vaccine doses or three doses plus BTI, in addition to vaccinated healthy donors (HD) and control patients treated with tumor necrosis factor inhibitor (TNFi). We quantified anti-SARS-CoV-2 receptor-binding domain (RBD) Spike IgG, anti-nucleocapsid (NC) IgG, 92 circulating inflammatory proteins, Spike-binding B cells, and Spike-specific T cells along with comprehensive high-dimensional phenotyping and functional assays.
Findings: The time since the last rituximab infusion, persistent inflammation, and age were associated with the anti-SARS-CoV-2 RBD IgG seroconversion. The vaccine-elicited serological response was accompanied by an incomplete induction of peripheral Spike-specific memory B cells but occurred independently of T cell responses. Vaccine- and BTI-elicited cellular immunity was similar between RA and HD ex vivo in terms of frequency or phenotype of Spike-specific cytotoxic T cells and in vitro in terms of the functionality and differentiation profile of Spike-specific T cells.
Interpretation: SARS-CoV-2 vaccination in RA can induce persistent effector T-cell responses that are reactivated by BTI. Paused rituximab medication allowed serological responses after a booster dose (D4), especially in RA with lower inflammation, enabling efficient humoral and cellular immunity after BTI, and contributed overall to the development of potential durable immunity.
Competing Interests: JV reports grants from the Coalition of Epidemic Preparedness Innovations. GG reports funding from the South-Eastern Norway Regional Health Authority, Dr. Trygve Gythfeldt og frues forskningsfond, Karin Fossum Foundation, the Research Foundation at Diakonhjemmet Hospital, speakers’ bureaus from AbbVie, Galapagos, Pfizer, and Union Chimique Belge; and participation on advisory board of AbbVie, Galapagos, Pfizer, and Union Chimique Belge. LM reports funding from the KG Jebsen Foundation, support for infrastructure and biobanking from the University of Oslo and Oslo University Hospital, grants from the Coalition of Epidemic Preparedness Innovations, RCN Covid 312693, a KG Jebsen Foundation grant 19, and speakers bureaus from Novartis, and Cellgene. EH reports grants from The Research Council of Norway during the conduct of the study; and for the last 36 months outside of the submitted work: speaker/consultant fees from Pfizer, AbbVie, Gilead, UCB Pharma, Galapagos, Eli Lilly, Novartis, Boehringer Ingelheim. KJ reports speaker fees from BMS and Janssen. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
(Copyright © 2024 Kared, Jyssum, Alirezaylavasani, Egner, The Tran, Tietze, Lund, Tveter, Provan, Ørbo, Haavardsholm, Vaage, Jørgensen, Syversen, Lund-Johansen, Goll and Munthe.)