Immunogenicity and risk of disease flare after a three-dose regimen of SARS-CoV-2 vaccination in patients with systemic lupus erythematosus: results from the prospective cohort study COVAC-SLE

Objective To investigate the humoral immune response and risk of disease flare in systemic lupus erythematosus (SLE) patients following three-doses of SARS-CoV-2 vaccines. Methods In adult patients with SLE, we measured SARS-CoV-2 spike IgG in blood samples drawn three weeks after the 1(st) dose (baseline), four and eight weeks after the 2(nd) dose and after the 3(rd) dose. A sufficient antibody response was >= 54BAU/mL. SLEDAI- 2K, SLAQ and SDI were assessed at baseline and eight weeks after the 2(nd) dose along with adverse events. Demographic and treatment data were collected from hospital records. Results Of 123 patients, 115 (93.5%) received the BNT162b2 vaccine, the remaining received the 1(st) dose of ChAdOx-1 followed by a 2(nd) and 3(rd) dose of mRNA- 1273. After the 2(nd) dose 102 (83%) patients had a sufficient antibody response (median 559.2, IQR 288.8-1180.5 BAU/mL), increasing to 115 (93.5%) (median 2416.9, IQR 1289-4603.8 BAU/mL) patients after the 3(rd) dose. Eight weeks after the 2(nd) dose patients treated with high dose prednisolone (p=0.034) and DMARDs (p<0.001) had significantly lower antibodies; however, this difference was not significant following the 3rd dose. Disease activity and damage were stable during the study period. Adverse events were more frequent in patients with a sufficient response. Breakthrough infections were reported in 39 (31.7%) patients; all with mild symptoms. Conclusion A 3rd dose improved the humoral response to SARS-CoV-2 vaccines in patients with SLE to the level of healthy individuals. Vaccination did not affect SLE disease activity. Subsequent breakthrough infections were mild and did not require hospitalisation.