RESUMEN
Objectives The humoral immune response to SARS-CoV-2 vaccination in patients with chronic inflammatory disease (CID) declines more rapidly with TNFα inhibition. Furthermore, the efficacy of current vaccines against Omicron variants of concern (VOC) including BA.2 is limited. Alterations within immune cell populations, changes in IgG affinity and the ability to neutralise a pre-VOC strain and the BA.2 virus were investigated in these at-risk patients. Methods Serum levels of anti-SARS-CoV-2 IgG, IgG avidity and neutralising antibodies (NA) were determined in anti-TNFα patients (n=10) and controls (n=24 healthy individuals; n=12 patients under other disease-modifying anti-rheumatic drugs, oDMARD) before and after the second and third vaccination by ELISA, immunoblot and live virus neutralisation assay. SARS-CoV-2-specific B-and T cell subsets were analysed by multicolour flow cytometry. Results IgG avidity and anti-pre-VOC NA titres decreased faster in anti-TNFα recipients than in controls 6 months after the second vaccination (healthy individuals: avidity: p≤0.0001; NA: p=0.0347; oDMARDs: avidity: p=0.0012; NA: p=0.0293). Total plasma cell counts were increased in anti-TNFα patients (Healthy individuals: p=0.0344; oDMARDs: p=0.0254), whereas absolute numbers of SARS-CoV-2-specific cells were comparable 7 days after vaccination. These patients had lower BA.2 NA titres compared to both other groups, even after the third vaccination. Conclusions We show a reduced SARS-CoV-2 neutralising capacity in patients under TNFα blockade. In this cohort, the plasma cell response appears to be less specific and show stronger bystander activation. While these effects were observable after the first two vaccinations and with older VOC, the differences in responses to BA.2 were magnified. What is already known on this topic Patients with chronic inflammatory diseases treated with TNFα inhibitors show a greater decrease in SARS-CoV-2 IgG 6 months after the second vaccination than patients taking oDMARDs and healthy individuals. What this study adds Antibodies from patients taking TNFα blockers have a lower SARS-CoV-2 neutralising capacity and maturity. Plasma cells from these patients exhibit less specific immune reaction. SARS-CoV-2-specific T cells are less activated. Neutralisation against BA.2 is drastically reduced even after the third vaccination. How this study might affect research, practice or policy This study emphasizes the need to protect vulnerable groups such as patients using TNF inhibitors. They could benefit from Omicron-adapted vaccination, but most likely they need to be protected by additional means other than vaccination.