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

OBJECTIVES: 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 1st dose (baseline), four and eight weeks after the 2nd dose and after the 3rd dose. A sufficient antibody response was ≥54BAU/mL. SLEDAI-2K, SLAQ and SDI were assessed at baseline and eight weeks after the 2nd 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 1st dose of ChAdOx-1 followed by a 2nd and 3rd dose of mRNA-1273. After the 2nd 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 3rd dose. Eight weeks after the 2nd 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. CONCLUSIONS: 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.

Bacillus Calmette-Guérin immunotherapy for bladder cancer: a review of immunological aspects, clinical effects and BCG infections.

Bacillus Calmette-Guérin (BCG) immunotherapy for bladder cancer has been used since 1976 when the first evidence of its ability to lower recurrence and progression rates was published. Today, BCG immunotherapy is the choice of care for high-grade non-muscle invasive bladder cancer (NMIBC) after transurethral resection. This article presents indications and procedure of BCG instillations, and outlines the effects on recurrence and progression of NMIBC. The BCG-induced immunity in NMIBC is not yet fully understood. Animal studies point towards BCG inducing specific tumour immunity. We describe the current knowledge of how this immunity is induced, from internalization of BCG bacilli in urothelial cells, to cytokine- and chemokine-mediated recruitment of neutrophils, monocytes, macrophages, T cells, B cells and natural killer cells. In addition, we describe the process of trained immunity, the non-specific protective effects of BCG. Recent studies also indicate that dysbiosis of the urinary microbiome may cause lower urinary tract dysfunction. Side effects of BCG bladder instillations range from common, mild and transient symptoms, such as dysuria and flu-like symptoms, to more severe and rarely occurring life-threatening complications. We review the literature and give an overview of reported incidences and management of BCG infections after intravesical instillation.