B Cell Reconstitution is Associated With COVID-19 Booster Vaccine Responsiveness in Patients Previously Seronegative Treated With Rituximab

Abstract

Objective: To assess factors associated with serologic response to the coronavirus 2019 (COVID-19) booster vaccine in patients with autoimmune rheumatic diseases treated with rituximab (RTX) who were previously serologically unresponsive to the initial vaccine series.

Methods: A retrospective chart review of patients treated with RTX 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 ≥ 4 weeks after the booster was the primary outcome. Fisher exact tests, t tests, and Wilcoxon rank-sum tests were used for comparisons.

Results: In 31 patients who were previously seronegative, 68% seroconverted following a booster of the COVID-19 vaccine. B cell reconstitution was significantly different between those with positive (median 1.79, IQR 0.65-3.00) and negative (median 0, IQR 0-0) serologic responses to the booster. The days from last RTX dose were also statistically different among seroconverters (median 301, IQR 251-368) vs nonseroconverters (median 188, IQR 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 vaccine. Positive predictive value of time ≥ 6 months from last RTX dose to booster was 78.3% (95% CI 56.3-92.5) and the negative predictive value was 62.5% (95% CI 24.5-91.5).

Conclusion: Detectable B cells and longer time from last RTX 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 patients treated with RTX.

Keywords: B lymphocytes; rheumatic diseases; vaccination.

Figure 1.

COVID-19 booster response by time from last RTX infusion and B cell status to antibody measurement. (A) Among patients with a negative serologic response, the median days from last infusion to COVID-19 booster vaccination was 188 (IQR 169–245) days. Patients with a positive serologic response had a median of 301 (IQR 251–368) days. Wilcoxon rank-sum test was used to calculate the P value. (B) The percentage of B cells among the negative serologic response median was 0 (IQR 0–0). Among the positive serologic vaccine response group, the median was 1.79 (IQR 0.65–3.00). The P value is from the Wilcoxon rank-sum test. The y-axis is the percentage of B cells in the total lymphocyte population. COVID-19: coronavirus disease 2019; RTX: rituximab.