Memory B cells (MBCs) are responsible for maintaining long-lasting functional B-cell immune responses. Little is known about the kinetics of peripheral blood (PB) SARS-CoV-2 vaccine-induced MBCs in end-stage chronic kidney disease (CKD) patients undergoing replacement therapies. We investigated this issue in this prospective, observational cohort study including 27 patients (9 females and 18 males; median age, 68.4 years, range 48-82) comprising 20 hemodialysis patients and 7 Kidney transplant recipients. SARS-CoV-2-Receptor-Binding Domain (RBD)-targeted PB-MBCs were enumerated by flow cytometry using a tetramer-binding assay after the second COVID-19 mRNA vaccine dose (Post-2D), before (Pre-3D), and after the first mRNA vaccine booster dose (Post-3D). Commercially available electrochemiluminescent immunoassays were used to measure total anti-RBD antibodies targeting an IgG against the S trimeric protein. Overall, 18/27 patients (66.6%) exhibited detectable RBD-MBC responses at Post-2D, 12/27 (44.4%) at Pre-3D, and 16/27 (59.2%) at Post-3D. RBD-MBC levels dropped non-significantly between post-2D and Pre-3D ( P=0.38). A non-significant increase in RBD-MBCs was noticed post-3D ( P=0.65). Overall, both antibody specificities displayed the same dynamics but the drop in anti-trimeric spike antibody levels between Post-2D and Pre-3D and increases post-3D were statistically significant ( P<0.001). No correlation (rho = 0.05; P=0.64) was observed between total antibodies against RBD and RBD-MBC counts. The correlation between IgG antibodies against the trimeric S protein and SARS-CoV-2 RBD-MBC counts was very weak (rho, 0.18; P=0.11). In summary, waning RBD-MBC counts Pre-3D and increases post-3D are less marked than that of anti-RBD and anti-S trimeric antibodies.

Background: It is unknown whether Torque Teno virus (TTV) DNA load monitoring could anticipate the development of infectious events in hematological patients undergoing treatment with small molecular targeting agents. We characterized the kinetics of plasma TTV DNA in patients treated with ibrutinib or ruxolitinib and assessed whether TTV DNA load monitoring could predict the occurrence of Cytomegalovirus (CMV) DNAemia or the magnitude of CMV-specific T-cell responses. Methods: Multicenter, retrospective, observational study, recruiting 20 patients treated with ibrutinib and 21 with ruxolitinib. Plasma TTV and CMV DNA loads were quantified by real-time PCR at baseline and days +15, +30, +45, +60, +75, +90, +120, +150, and +180 after treatment inception. Enumeration of CMV-specific IFN-γ-producing CD8 + and CD4 + T cells in whole blood was performed by flow cytometry. Results: Median TTV DNA load in ibrutinib-treated patients increased significantly ( P=0.025) from baseline (median, 5.76 log 10 copies/ml) to day +120 (median, 7.83 log 10 copies/ml). A moderate inverse correlation (Rho=-0.46; P<0.001) was found between TTV DNA load and absolute lymphocyte count (ALC). In ruxolitinib-treated patients, TTV DNA load quantified at baseline was not significantly different from that measured after treatment inception ( P ≥0.12). TTV DNA loads were not predictive of the subsequent occurrence of CMV DNAemia in either patient group. No correlation was observed between TTV DNA loads and CMV-specific IFN-γ-producing CD8 + and CD4 + T cell counts in either patient group. Conclusion: The data did not support the hypothesis that TTV DNA load monitoring in hematological patients treated with ibrutinib or ruxolitinib could be useful to predict either the occurrence of CMV DNAemia or the level of CMV-specific reconstitution.