Background. Patients on kidney replacement therapy comprise a vulnerable population and may be at increased risk of death from coronavirus disease 2019 (COVID-19). Currently, only limited data are available on outcomes in this patient population. Methods. We set up the ERACODA (European Renal Association COVID-19 Database) database, which is specifically designed to prospectively collect detailed data on kidney transplant and dialysis patients with COVID-19. For this analysis, patients were included who presented between 1 February and 1 May 2020 and had complete information available on the primary outcome parameter, 28-day mortality. Results. Of the 1073 patients enrolled, 305 (28%) were kidney transplant and 768 (72%) dialysis patients with a mean age of 60 ± 13 and 67 ± 14 years, respectively. The 28-day probability of death was 21.3% [95% confidence interval (95% CI) 14.3–30.2%] in kidney transplant and 25.0% (95% CI 20.2–30.0%) in dialysis patients. Mortality was primarily associated with advanced age in kidney transplant patients, and with age and frailty in dialysis patients. After adjusting for sex, age and frailty, in-hospital mortality did not significantly differ between transplant and dialysis patients [hazard ratio (HR) 0.81, 95% CI 0.59–1.10, P = 0.18]. In the subset of dialysis patients who were a candidate for transplantation (n = 148), 8 patients died within 28 days, as compared with 7 deaths in 23 patients who underwent a kidney transplantation <1 year before presentation (HR adjusted for sex, age and frailty 0.20, 95% CI 0.07–0.56, P < 0.01). Conclusions. The 28-day case-fatality rate is high in patients on kidney replacement therapy with COVID-19 and is primarily driven by the risk factors age and frailty. Furthermore, in the first year after kidney transplantation, patients may be at increased risk of COVID-19-related mortality as compared with dialysis patients on the waiting list for transplantation. This information is important in guiding clinical decision-making, and for informing the public and healthcare authorities on the COVID-19-related mortality risk in kidney transplant and dialysis patients.

Ceftaroline fosamil demonstrated high clinical cure and microbiological response rates in hospitalized patients with CAP of PORT risk class III or IV. Ceftaroline fosamil was well tolerated, with a safety profile similar to that of ceftriaxone and consistent with the cephalosporin class. In this study, ceftaroline fosamil was an effective and well-tolerated treatment option for CAP.

SummaryThe relationships between tissue plasminogen activator (tPA), its fast acting inhibitor (PAI-1) and euglobulin clot lysis time (ELT) were investigated with healthy volunteers’ plasma. Turbidimetric clot lysis assay by the microtiter plate reader was utilized for ELT with a slight modification. Both tPA and PAI-1 showed the significant correlation with ELT. tPA had a significantly positive, not negative, correlation with ELT (R = 0.387, p <0.001). Higher correlation coefficients (R = 0.580, p <0.001 and R = 0.599, p <0.001) were obtained between ELT and total PAI-1 or free PAI-1 than tPA or tPA-PAI-1 complex (R = 0.427, p <0.001). The positive correlation was also obtained between tPA and PAI-1. These data suggest that PAI-1 is a highly important factor for ELT, especially, the amounts of free PAI-1 being the key factor to determine the ELT, which can represent the potential activity of the fibrinolytic system.

Background COVID-19 has exposed hemodialysis patients and kidney transplant recipients to an unprecedented life-threatening infectious disease raising concerns about kidney replacement therapy (KRT) strategy during the pandemic. The present study investigated the association of type of KRT with COVID-19 severity adjusting for differences in individual characteristics. Methods Data on kidney transplant recipients and hemodialysis patients diagnosed with COVID-19 between February 1st and December 1st 2020 were retrieved from ERACODA. Cox regression models adjusted for age, sex, frailty and comorbidities were used to estimate hazard ratios (HR) for 28-day mortality risk in all patients and in the subsets who were tested because of symptoms Results In total, 1,670 patients (496 functional kidney transplant and 1,174 hemodialysis) were included. 16.9% of kidney transplant and 23.9% of hemodialysis patients died within 28 days of presentation. The unadjusted 28-day mortality risk was 33% lower in kidney transplant recipients compared with hemodialysis patients (HR: 0.67, 95%CI: 0.52-0.85). In a fully adjusted model, the risk was 78% higher in kidney transplant recipients (HR: 1.78, 95%CI: 1.22-2.61) compared with hemodialysis patients. This association was similar in patients tested because of symptoms (fully adjusted model HR: 2.00, 95%CI: 1.31-3.06). This risk was dramatically increased during the first post-transplant year. Results were similar for other endpoints (e.g. hospitalization, ICU admission, mortality beyond 28 days) and across subgroups. Conclusions Kidney transplant recipients had a greater risk of a more severe course of COVID-19 compared with hemodialysis patients; they therefore require specific infection mitigation strategies.

The registry data focused new light on the epidemiology of kidney diseases in Poland. These data should be used in future follow-up and prospective studies.

Objective The aim of the study was to investigate efficacy and safety of convalescent plasma (CP) transfusion in a group of high-risk COVID-19 patients. Methods This prospective study included 204 patients from a single tertiary-care hospital, hospitalized with COVID-19, of whom 102 were treated with CP administration and standard care (PG) and 102 others who received standard care only (CG). The CG was selected from 336 hospitalized patients using the propensity score matching (PSM) technique using age, MEWS score, and comorbidities. The primary outcome was mortality rate; secondary outcomes were the requirement of ventilator, length of ventilator need, length of intensive care unit (ICU) stay, and length of overall hospital confinement. Additionally, parameters predicting death in COVID-19 patients were identified. Results Findings confirmed a significantly lower mortality rate in the PG versus the CG (13.7% vs. 34.3 %, p = 0.001) and a significant difference in cumulative incidence of death between the two groups ( p < 0.001). CP treatment was associated to lower risk of death ( OR = 0.25 CI 95 [0.06; 0.91], p = 0.041). There were no significant differences in ICU stay, ventilator time, and hospitalization time between the two groups. Conclusions A significantly lower mortality rate was observed in the group of patients treated with CP. Age, presence of cardiac insufficiency, active cancer, requirement of ventilator, and length of hospitalization were significantly increasing the risk of death in both groups. Our study shows, that CP brings better outcomes when administrated in the earlier stage of high-risk COVID-19 disease.

No abstract

SummaryHuman protein S (HPS) has three potential N-linked glycosylation sites at Asn458’468’489. To study the role of glycosylation at these sites, PCR mutagenesis was used to abolish the consensus sequence of each N-linked glycosylation site (Asn458→Gln, Ser460→Gly; Asn468→Gln, Thr470→Gly; Asn489→Gln, Thr491→Gly) in full-length HPS cDNA. Each resulting construct was expressed in human kidney 293 cells by stable transfection of cDNA/SV40/adeno/pBR322-derived expression vectors, and conditioned medium was collected for recombinant protein purification. SDS-PAGE gels revealed that glycosylation mutants migrate identically and faster than the wild-type rHPS, showing that each of the three potential N-glycosylation sites contain a similar amount of carbohydrate. Mass spectral analysis yielded similar results and a molecular mass of ~78,000 for wild-type HPS. To demonstrate that the difference in mobility between wild-type and mutant protein S is due to their carbohydrate content, plasma-derived HPS and recombinant HPS were subjected to N-glycanase digestion and subsequently shown to migrate identically on SDS-PAGE gels. All forms of HPS have similar time courses for cleavage by α-thrombin. Functional studies indicate that wild-type rHPS possesses the same cofactor specific activity as plasma-derived HPS, as tested by a standard clotting assay. Asn458 and Ser460 mutant rHPS have only a slightly higher cofactor activity, whereas the other four mutants have similar clotting activities, compared to wild-type rHPS. In a purified component system, glycosylation mutants of protein S showed a slightly enhanced ability to stimulate APC-mediated factor Va inactivation after an initial lag phase. The interaction of rHPS glycosylation mutants with human C4b-binding protein (C4bp) was also studied by solution phase equilibrium binding assay. Two mutants (Asn458, Ser460) have marginally lower dissociated constants (Kd) with C4bp, whereas the others have the same apparent Kd as wild-type rHPS.