Infection or a third dose of mRNA vaccine elicits neutralizing antibody responses against SARS-CoV-2 in kidney transplant recipients.

Transplant recipients, who receive therapeutic immunosuppression to prevent graft rejection, are characterized by high coronavirus disease 2019 (COVID-19)-related mortality and defective response to vaccines. We observed that previous infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), but not the standard two-dose regimen of vaccination, provided protection against symptomatic COVID-19 in kidney transplant recipients. We therefore compared the cellular and humoral immune responses of these two groups of patients. Neutralizing anti-receptor-binding domain (RBD) immunoglobulin G (IgG) antibodies were identified as the primary correlate of protection for transplant recipients. Analysis of virus-specific B and T cell responses suggested that the generation of neutralizing anti-RBD IgG may have depended on cognate T-B cell interactions that took place in germinal center, potentially acting as a limiting checkpoint. High-dose mycophenolate mofetil, an immunosuppressive drug, was associated with fewer antigen-specific B and T follicular helper (TFH) cells after vaccination; this was not observed in patients recently infected with SARS-CoV-2. Last, we observed that, in two independent prospective cohorts, administration of a third dose of SARS-CoV-2 mRNA vaccine restored neutralizing titers of anti-RBD IgG in about 40% of individuals who had not previously responded to two doses of vaccine. Together, these findings suggest that a third dose of SARS-CoV-2 mRNA vaccine improves the RBD-specific responses of transplant patients treated with immunosuppressive drugs.

Cytomegalovirus disease in de novo kidney-transplant recipients: comparison of everolimus-based immunosuppression without prophylaxis with mycophenolic acid-based immunosuppression with prophylaxis.

PURPOSE: To compare everolimus (EVR) plus low-dose tacrolimus (TAC) with mycophenolic acid (MPA) plus standard-dose TAC with regards to rates of cytomegalovirus (CMV) disease in de novo kidney-transplant recipients (KTRs). METHODS: This single-center retrospective study included 187 de novo KTRs; 59 patients (31.6%) received EVR/low-dose TAC (group 1); 128 patients (68.4%) received MPA with standard-dose TAC (group 2). All received anti-thymocyte globulins as the induction therapy, and steroid-sparing strategy. Valganciclovir prophylaxis was mandatory for CMV D+/R- KTRs (seronegative recipients of a seropositive donor) in both groups and for R+ seropositive recipients (only in group 2). RESULTS: The 2-year incidence of CMV disease was low and comparable between groups: 6.8% and 7.0% in groups 1 and 2, respectively (p = 0.94). There was no statistical difference in CMV serostatus (p = 1). However, CMV disease tended to be less frequent, though not statistically different, in R+ KTRs receiving EVR without prophylaxis (3.7% vs. 8.5% in groups 1 and 2, respectively) and in patients without EVR discontinuation (2.6% vs. 6.9% in patients who did not discontinue MPA (p = 0.29). Two-year graft function was good and comparable between groups (median eGFR of 54.2 and 53.0 mL/min in groups 1 and 2, respectively; p = 0.47); incidence of immunological events was low. Significantly more patients in group 1 discontinued EVR because of adverse events than patients that discontinued MPA in group 2 (35.6% in group 1 vs. 10.2% in group 2; p < 0.001). CONCLUSIONS: Everolimus plus low-dose TAC given to de novo KTRs was associated with low rates of CMV disease, especially in R+ patients with no CMV prophylaxis.

An Atypical Case of Shiga Toxin Producing-Escherichia Coli Hemolytic and Uremic Syndrome (STEC-HUS) in a Lung Transplant Recipient.

We herein describe the first case of thrombotic microangiopathy (TMA) which was related to Shiga toxin producing-Escherichia Coli Hemolytic and Uremic Syndrome (STEC-HUS) after lung transplantation. His maintenance immunosuppression relied on tacrolimus plus mycophenolic acid. TMA was treated with plasma exchanges (PE) (fresh frozen plasma substitution). After five days of PE, platelets count and lactate dehydrogenase level normalized, whereas hemoglobin continued to gradually decrease and no improvement in kidney function was observed. After seven PE sessions, all TMA biological signs resolved. However, kidney function did not improve, and the patient still required chronic dialysis.

Investigating the temporal dynamics of suspended sediment during flood events with 7Be and 210Pbxs measurements in a drained lowland catchment.

Soil erosion is recognized as one of the main processes of land degradation in agricultural areas. High suspended sediment loads, often generated from eroding agricultural landscapes, are known to degrade downstream environments. Accordingly, there is a need to understand soil erosion dynamics during flood events. Suspended sediment was therefore sampled in the river network and at tile drain outlets during five flood events in a lowland drained catchment in France. Source and sediment fallout radionuclide concentrations (7Be, 210Pbxs) were measured to quantify both the fraction of recently eroded particles transported during flood events and their residence time. Results indicate that the mean fraction of recently eroded sediment, estimated for the entire Louroux catchment, increased from 45 ± 20% to 80 ± 20% between December 2013 and February 2014, and from 65 ± 20% to 80 ± 20% in January 2016. These results demonstrate an initial flush of sediment previously accumulated in the river channel before the increasing supply of sediment recently eroded from the hillslopes during subsequent events. This research highlights the utility of coupling continuous river monitoring and fallout radionuclide measurements to increase our understanding of sediment dynamics and improve the management of soil and water resources in agricultural catchments.