B-cell reconstitution is associated with COVID-19 booster vaccine responsiveness in previously seronegative rituximab treated patients

To assess factors associated with serologic response to the COVID-19 booster vaccine in rituximab-treated autoimmune rheumatic disease patients previously serologically unresponsive to the initial vaccine series.A retrospective chart review of rituximab-treated patients who failed to demonstrate a serologic response to the first SARS-CoV-2 vaccination series and subsequently received an mRNA vaccine booster was performed. Serologic response four weeks or more after the booster was the primary outcome. T-tests, Fisher's exact tests, and Wilcoxon rank sum tests were used for comparisons.In 31 previously seronegative patients, 68% seroconverted following a booster of the COVID-19 vaccine. B-cell reconstitution was significantly different between those with positive (median, IQR 1.785 (0.65, 3)) and negative (median, IQR 0 (0,0)) serologic responses to the booster. Days from last rituximab dosage was also statistically different among seroconverters (median, IQR 301 (251, 368)) versus non-seroconverters (median, IQR 188 (169, 245)). Demographic characteristics were not associated with serologic positivity. Positive predictive value of B-cell presence was 90.9% (95% CI: 70.8%, 98.9%) and negative predictive value was 100% (95% CI: 59%, 100%) for serologic response to the mRNA booster. Positive predictive value of time >6 months from last rituximab to the booster was 78.3% (95% CI 56.3%, 92.5%) and the negative predictive value was 62.5% (95% CI 24.5%, 91.5%).Detectable B-cells and longer time from last rituximab exposure were associated with the development of anti-SARS-CoV-2 spike protein antibodies following the booster vaccine. These findings should be considered in timing boosters in rituximab-treated patients.