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.

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.

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It is critical to protect immunocompromised patients against COVID-19 with effective SARS-CoV-2 vaccination as they have an increased risk of developing severe disease. This is challenging, however, since effective mRNA vaccination requires the successful cooperation of several components of the innate and adaptive immune systems, both of which can be severely affected/deficient in immunocompromised people. In this article, we first review current knowledge on the immunobiology of SARS-COV-2 mRNA vaccination in animal models and in healthy humans. Next, we summarize data from early trials of SARS-COV-2 mRNA vaccination in patients with secondary or primary immunodeficiency. These early clinical trials identified common predictors of lower response to the vaccine such as anti-CD19, anti-CD20 or anti-CD38 therapies, low (naive) CD4+ T-cell counts, genetic or therapeutic Bruton tyrosine kinase deficiency, treatment with antimetabolites, CTLA4 agonists or JAK inhibitors, and vaccination with BNT162b2 versus mRNA1273 vaccine. Finally, we review the first data on third dose mRNA vaccine administration in immunocompromised patients and discuss recent strategies of temporarily holding/pausing immunosuppressive medication during vaccination.

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Rationale & Objective Patients on kidney replacement therapy (KRT) are at a very high risk of COVID-19. Triage pathway for KRT patients presenting with varying severity of COVID-19 illness remains ill-defined. We studied clinical characteristics of patients at initial and subsequent hospital presentations and its impact on patient outcomes. Study Design, Setting, Participants European Renal Association COVID-19 Database (ERACODA) was analysed for clinical and laboratory features of 1423 KRT patients with COVID-19 either hospitalized or non-hospitalized during first presentation and those representing after non-admission at initial triage. Predictors of outcomes (Hospitalisation, 28-day mortality) were determined for those not hospitalized at first presentation. Results Amongst 1423 KRT patients with COVID-19 (Hemodialysis = 1017/Transplant = 406), 25% (n = 355) were not hospitalized at first presentation (30% Hemodialysis/13% Transplant). Of these non-hospitalized patients, 10% (n = 36) re-presented second time, with a 5-day median interval between two presentations (Interquartile interval 2-7 days). Patients who re-presented had worsening respiratory symptoms, a fall in oxygen saturation (97% vs. 90%) and rise in C-reactive protein between attendances (26 vs. 73 mg/L). Patients on second presentation were older (72 vs. 63 years), had early respiratory symptoms and lung imaging abnormalities compared with those who did not return second time. The 28-day mortality for those admitted at first or second presentations was not significantly different (25% vs. 29%, p = 0.6). Higher age, prior smoking history, higher clinical frailty score and self-reported shortness of breath at first presentation, were identified as predictors of mortality in those discharged at initial triage. Conclusions The study provides evidence that KRT patients with COVID-19 and mild pulmonary abnormalities with lack of pulmonary insufficiency can be safely discharged, with vigilance of respiratory symptoms, especially in those with risk factors for poor outcomes. Our findings support a risk-stratified clinical approach to admissions and discharges of KRT patients presenting with COVID-19, to aid clinical triage and optimise resource utilisation during the ongoing pandemic.

Background Several guidelines recommend using the Clinical Frailty Scale (CFS) for triage of critically ill COVID-19 patients. This study evaluates the impact of CFS on intensive care unit (ICU) admission rate, and hospital- and ICU mortality rates in hospitalized dialysis patients with COVID-19. Methods We analysed data of dialysis patients diagnosed with COVID-19 from the European Renal Association COVID-19 Database. The primary outcome was ICU admission rate and secondary outcomes were hospital- and ICU mortality until 3 months after COVID-19 diagnosis. Cox regression analyses were performed to assess associations between CFS and outcomes. Results 1501 dialysis patients were hospitalized due to COVID-19, of whom 219 (15%) were admitted to an ICU. ICU admission rate was lowest (5%) in patients >75 years with CFS 7-9 and highest (27%) in patients 65-75 years with CFS 5. CFS 7-9 was associated with a lower ICU admission rate than CFS 1-3 (RR 0.49; 95%CI 0.27-0.87). Overall, mortality at three months was 34% in hospitalized patients, 65% in ICU admitted patients and highest in patients >75 years with CFS 7-9 (69%). Only 9% of patients with CFS ≥6 survived after ICU admission. After adjustment for age and sex, each CFS category ≥4 was associated with higher hospital and ICU mortality compared with CFS 1-3. Conclusions Frail dialysis patients with COVID-19 were less frequently admitted to the ICU. Large differences in mortality rates between fit and frail patients suggest that CFS may be a useful complementary triage tool for ICU admission in dialysis patients with COVID-19.

As solid organ recipients are at high risk of severe COVID-19 and respond poorly to primary SARS-CoV-2 mRNA vaccination, they have been prioritized for booster vaccination. However, an immunological correlate of protection has not been identified in this vulnerable population. We conducted a prospective monocentric cohort study of 65 kidney transplant recipients who received three doses of SARS-CoV-2 BNT162b2 mRNA vaccination. Associations between symptomatic breakthrough infection (BTI) and vaccine responses, patient demographic and clinical characteristics were explored. Symptomatic COVID-19 was diagnosed in 32% of kidney transplant recipients during a period of six months after the administration of the third vaccine dose. During this period, SARS-CoV-2 delta and omicron were the dominant variants in the general population. Univariate analyzes identified avidity of SARS-CoV-2 receptor binding domain (RBD) binding IgG, neutralizing antibodies and SARS-CoV-2 S2 domain-specific IFN-gamma responses as correlates of protection against BTI. Some demographic and clinical parameters correlated with vaccine responses, but none correlated with the risk of BTI. In multivariate analysis, the risk of BTI was best predicted by neutralizing antibody and S2-specific IFN-gamma responses, adjusting for age, graft function and mycophenolate mofetil use. In conclusion, both antibody and T cell responses predict the risk of BTI in kidney transplant recipients who received three doses of SARS-CoV-2 mRNA vaccine. T cell responses may help compensate for the suboptimal antibody response to vaccination in this vulnerable population.