We report the nationwide experience with solid organ transplant (SOT) and hematopoietic stem cell transplant (HSCT) recipients diagnosed with coronavirus disease 2019 (COVID-19) in Spain until 13 July 2020. We compiled information for 778 (423 kidney, 113 HSCT, 110 liver, 69 heart, 54 lung, 8 pancreas, 1 multivisceral) recipients. Median age at diagnosis was 61 years (interquartile range [IQR]: 52-70), and 66% were male. The incidence of COVID-19 in SOT recipients was two-fold higher compared to the Spanish general population. The median interval from transplantation was 59 months (IQR: 18-131). Infection was hospital-acquired in 13% of cases. No donor-derived COVID-19 was suspected. Most patients (89%) were admitted to the hospital. Therapies included hydroxychloroquine (84%), azithromycin (53%), protease inhibitors (37%), and interferon-β (5%), whereas immunomodulation was based on corticosteroids (41%) and tocilizumab (21%). Adjustment of immunosuppression was performed in 85% of patients. At the time of analysis, complete follow-up was available from 652 patients. Acute respiratory distress syndrome occurred in 35% of patients. Ultimately, 174 (27%) patients died. In univariate analysis, risk factors for death were lung transplantation (odds ratio [OR]: 2.5; 95% CI: 1.4-4.6), age >60 years (OR: 3.7; 95% CI: 2.5-5.5), and hospital-acquired COVID-19 (OR: 3.0; 95% CI: 1.9-4.9).

Background: Improving cytomegalovirus (CMV) immune-risk stratification in kidney transplantation is highly needed to establish guided preventive strategies. Methods: This prospective, interventional, multicenter clinical trial assessed the value of monitoring pretransplant CMV-specific cell-mediated immunity (CMI) using an interferon-γ release assay to predict CMV infection in kidney transplantation. One hundred sixty donor/recipient CMV-seropositive (D+/R+) patients, stratified by their baseline CMV (immediate-early protein 1)–specific CMI risk, were randomized to receive either preemptive or 3-month antiviral prophylaxis. Also, 15-day posttransplant CMI risk stratification and CMI specific to the 65 kDa phosphoprotein (pp65) CMV antigen were investigated. Immunosuppression consisted of basiliximab, tacrolimus, mycophenolate mofetil, and corticosteroids in 80% of patients, whereas 20% received thymoglobulin induction therapy. Results: Patients at high risk for CMV based on pretransplant CMI developed significantly higher CMV infection rates than those deemed to be at low risk with both preemptive (73.3% vs 44.4%; odds ratio [OR], 3.44 [95% confidence interval {CI}, 1.30–9.08]) and prophylaxis (33.3% vs 4.1%; OR, 11.75 [95% CI, 2.31–59.71]) approaches. The predictive capacity for CMV-specific CMI was only found in basiliximab-treated patients for both preemptive and prophylaxis therapy. Fifteen-day CMI risk stratification better predicted CMV infection (81.3% vs 9.1%; OR, 43.33 [95% CI, 7.89–237.96]). Conclusions: Pretransplant CMV-specific CMI identifies D+/R+ kidney recipients at high risk of developing CMV infection if not receiving T-cell–depleting antibodies. Monitoring CMV-specific CMI soon after transplantation further defines the CMV infection prediction risk. Monitoring CMV-specific CMI may guide decision making regarding the type of CMV preventive strategy in kidney transplantation. Clinical Trials Registration: NCT02550639.

Background. Cytomegalovirus (CMV) infection remains a major complication after kidney transplantation. Baseline CMV risk is typically determined by the serological presence of preformed CMV-specific immunoglobulin (Ig) G antibodies, even though T-cell responses to major viral antigens are crucial when controlling viral replication. Some IgG-seronegative patients who receive an IgG-seropositive allograft do not develop CMV infection despite not receiving prophylaxis. We hypothesized that a more precise evaluation of pretransplant CMV-specific immune-sensitization using the B and T-cell enzyme-linked immunospot assays may identify CMV-sensitized individuals more accurately, regardless of serological evidence of CMV-specific IgG titers. Methods. We compared the presence of preformed CMV-specific memory B and T cells in kidney transplant recipients between 43 CMV IgG–seronegative (sR⁻) and 86 CMV IgG–seropositive (sR⁺) patients. Clinical outcome was evaluated in both groups. Results. All sR⁺ patients showed a wide range of CMV-specific memory T- and B-cell responses. High memory T- and B-cell frequencies were also clearly detected in 30% of sR⁻ patients, and those with high CMV-specific T-cell frequencies had a significantly lower incidence of late CMV infection after prophylactic therapy. Receiver operating characteristic curve analysis for predicting CMV viremia and disease showed a high area under the receiver operating characteristic curve (>0.8), which translated into a high sensitivity and negative predictive value of the test. Conclusions. Assessment of CMV-specific memory T- and B-cell responses before kidney transplantation among sR⁻ recipients may help identify immunized individuals more precisely, being ultimately at lower risk for CMV infection.

Background. It has been suggested that hepcidin may be useful as a tool for managing iron therapy in haemodialysis (HD) patients on erythropoiesis-stimulating agents (ESA). Methods. We used SELDI-TOF mass spectrometry assay to measure serum hepcidin-25 (Hep-25) and hepcidin-20 (Hep-20) in 56 adult HD patients on maintenance ESA to assess their ability to predict haemoglobin (Hb) response after 1 g intravenous iron (62.5 mg ferric gluconate at 16 consecutive dialysis sessions) and their relationship with markers of iron status, inflammation and erythropoietic activity. Results. At multivariate analysis (in a model that also included Hb, reticulocyte, ESA dose, HFE genotype, soluble transferrin receptor [sTfR] and C-reactive protein), Hep-25 independently correlated with ferritin (β = 0.03, P = 0.01) and the percentage of hypochromic red blood cells [%Hypo] (β = 1.84, P = 0.01), suggesting that Hep-25 may be a useful biomarker for iron stores and bone marrow iron availability. Hep-20 correlated independently with Hep-25 (β = 0.159, P < 0.001) and ferritin (β = 0.006, P = 0.05), suggesting that it may be a useful additional biomarker for iron stores. On receiver operating characteristics curve analysis, neither Hep-25 nor Hep-20 significantly predicted who will increase their Hb after iron loading (AUC = 0.52 ± 0.09 and 0.54 ± 0.08, P = 0.612), and the same applied to ferritin and transferrin saturation (AUC = 0.55 ± 0.08 and 0.59 ± 0.08, P = 0.250), whereas %Hypo and reticulocyte Hb content were significant predictors (AUC = 0.84 ± 0.05 and 0.70 ± 0.08, P < 0.01). At multivariate logistic regression analysis, %Hypo was the only biomarker independently associated with iron responsiveness. Conclusions. Although our study suggests an important role for hepcidin in regulating iron homeostasis in HD patients on ESA, our findings do not support its utility as a predictor of iron needs, offering no advantage over established markers of iron status.

Presence of subclinical rejection (SCR) with IF/TA in protocol biopsies of renal allografts has been shown to be an independent predictor factor of graft loss. Also, intragraft Foxp3+ T_reg cells in patients with SCR has been suggested to differentiate harmful from potentially protective infiltrates. Nonetheless, whether presence of Foxp3 T_reg cells in patients with SCR and IF/TA may potentially protect from a deleterious graft outcome has not yet been evaluated. This is a case-control study in which 37 patients with the diagnosis of SCR and 68 control patients with no cellular infiltrates at 6-month protocol biopsies matched for age and time of transplantation were evaluated. We first confirmed that numbers of intragraft Foxp3-expressing T cells in patients with SCR positively correlates with Foxp3 demethylation at the T_reg-specific demethylation region. Patients with SCR without Foxp3+ T_reg cells within graft infiltrates showed significantly worse 5-year graft function evolution than patients with SCR and Foxp3+ T_reg cells and those without SCR. When presence of SCR and IF/TA were assessed together, presence of Foxp3+ T_reg could discriminate a subgroup of patients showing the same graft outcome as patients with a normal biopsy. Thus, presence of Foxp3+ T_reg cells in patients with SCR even with IF/TA is associated with a favorable long-term allograft outcome.