ABSTRACT
Background: At the start of the COVID-19 pandemic, kidney transplant recipients (KTR) were warned for a high risk of complications in case of infection. After SARSCoV-2 vaccination, KTR appeared to still be at risk of fatal COVID-19 disease, especially when they had limited or no antibody formation. The aim of this study was to describe the self-reported change in behavior of KTR before and after SARS-CoV-2 vaccination in groups with different antibody responses. Method(s): Questionnaires were sent to 2793 KTR, asking for adherence to preventive measures before vaccination, after vaccination and after receiving their level of antibody response. Adherence was reported on a 5-point Likert scale. From April till June 2021 blood samples were collected measuring anti-spike IgG by ELISA 28 days after full SARS-CoV-2 vaccination. Participants were categorized based on antibody response to vaccination as non-responder (<=50 BAU/mL), low-responder (>50 <=300 BAU/mL) or responder (>300 BAU/mL), which was shared with the participant as a correlate of protection. Adherence to preventive measures before vaccination was compared with the two time points after vaccination by the Wilcoxon signed rank sum test. The impact of category on adherence was measured by ordinal logistic regression, taking non-responder as reference. Result(s): The median antibody titer was 7 BAU/mL in the non-(N=1109), 122 BAU/mL in the low-(N=564) and 1751 BAU/mL in the responder cohort (N=1120). Of all preventive measures, adherence to 'keep 1.5 m distance', 'avoid supermarket or shops' and 'rules for visitors or visits' was significantly higher (p<0.001) before than after vaccination within all cohorts. Adherence was decreased among participants, with a dose response effect, who were informed of being a (low-) responder compared to KTR with no antibody response. Conclusion(s): SARS-CoV-2 vaccination in KTR leads to decreased adherence to some, but not all preventive measures, even when the antibody response was absent or low. A greater decrease in adherence was seen in (low)-responders to vaccination.
ABSTRACT
BACKGROUND AND AIMS: during the COVID-19 pandemic, several guidelines have recommended the use of the Clinical Frailty Scale (CFS) for triage of critically ill patients with COVID-19 in case of shortage in ICU resources. However, no data on using CFS assessment for ICU triage for dialysis patients is yet available. This study evaluates whether CFS is associated with mortality rates in a cohort of hospitalized dialysis patients with COVID-19. METHOD: the analyses are based on data of the European Renal Association COVID-19 Database (ERACODA). Dialysis patients who presented with COVID-19 between 1 February 2020 and 30 April 2021 and with complete information on CFS and vital status at 3 months were included. Study outcomes were hospital and ICU admission rates and hospital and ICU mortality at 3 months after hospital admission. Cox regression analyses were performed to assess the association of CFS category (≤5 versus ≥ 6) and study outcomes in line with Dutch ICU triage guidelines for COVID-19. Furthermore, additional subgroup analyses were performed to assess the association between CFS and 3-month mortality by age category (<65, 65-75 and >75 years). RESULTS: among a total of 2206 dialysis patients (mean age = 67.2 (14.1) years, male sex = 61%), 1694 (77%) had CFS ≤ 5 and 514 (23%) had CFS ≥ 6. Hospitalization rate was comparable in patients with CFS ≤ 5 and in patients with CFS ≥ 6 (67 and 71%, respectively), whereas the rate of ICU admission was higher in patients with CFS ≤ 5 than in patients with CFS ≥ 6 (16 versus 9%, p = 0.001). Among 1501 hospitalized patients, 3-month mortality was 26% of patients with CFS ≤ 5 and 59% in patients with CFS ≥ 6 (P < 0.001). Multivariate analysis with adjustment for patient demographics, smoking status and BMI revealed that CFS ≥ 6 was associated with hospital mortality [aHR 2.27 (1.88-2.74) versus CFS ≤ 5;P < 0.001) with a significant interaction for age (P = 0.029). aHR was 4.00 (2.56-6.37;CFS ≥ 6 versus CFS ≤ 5;P < 0.001) in patients < 65 years, aHR was 1.87 (1.33-2.64;CFS ≥ 6 versus CFS ≤ 5;P < 0.001) in patients 65-75 years and aHR was 2.12 (1.64-2.75;CFS ≥ 6 versus CFS ≤ 5;P < 0.001) in patients >75 years. Among 219 ICU admitted patients, 3-month mortality was 60% of the patients with CFS ≤ 5 and 91% in the patients with CFS ≥ 6, respectively. Multivariate analysis with adjustment for patient demographics, smoking status and BMI revealed that CFS ≥ 6 was associated with ICU mortality [aHR 1.80 (1.17-2.77);CFS ≥ 6 versus CFS ≤ 5;P = 0.002]. CONCLUSION: more frail dialysis patients with CFS ≥ 6 who are hospitalized for COVID-19 were less often admitted to the ICU, but in case they were admitted to the ICU they have a very high mortality of 91% in this cohort study. In fit to mildly frail dialysis, patients who were admitted to the ICU, mortality rates are lower. The association between frailty and hospital mortality is interacted by age with the strongest association in patients younger than 65 years. These findings suggest that CFS may be a useful complementary triage tool for ICU admission of dialysis patients during the ongoing COVID-19 pandemic.
ABSTRACT
BACKGROUND AND AIMS: Patients on kidney replacement therapy (KRT) are at a particularly high risk of mortality from COVID-19. In this study, we investigated COVID-19 mortality in KRT patients in the first and second waves of the pandemic and potential reasons for any difference in mortality between the two waves. METHOD: Data from the European Renal Association COVID-19 Database (ERACODA) of KRT patients who presented between 1 March 2020 and 28 February 2021 with COVID-19 were analyzed. The cut-off for dividing the first and second waves was set for 1 August 2020. The primary study outcome was 28-day mortality. Multivariable Cox proportional-hazards regression analysis was used to examine the relationship between the pandemic waves and mortality with follow-up time starting at the date of presentation. Dialysis patients and kidney transplant recipients were analyzed separately. RESULTS: Among 3004 dialysis patients (1253 in the first and 1751 in the second wave), the 28-day mortality was 24.3% in the first wave and 19.6% in the second wave (P = .002). Compared with the first wave, in the second wave, identification of patients with limited to no symptoms was higher (14.3% versus 24.8%;P < .001), hospitalization was lower (71.3% versus 44.3%;P < .001), but in-hospital mortality was similar (30.4% versus 30.7%;P = .92) (Fig. 1). Crude hazard ratio (HR) for 28-day mortality in the second wave was 0.77 (95% CI: 0.66, 0.89). However, in a fully adjusted model, when correcting for differences in patient and disease characteristics, including the reason for COVID-19 screening and disease severity, the HR for mortality in the second wave was 0.93 [95% confidence interval (95% CI): 0.79-1.10]. When follow-up was chosen to start at the date of first symptoms to account for possible lead-time bias, crude HR for 28-day mortality in the second wave was 0.90 (95% CI: 0.75-1.07) and the fully adjusted HR was 0.98 (95% CI: 0.81-1.18). Among 1035 kidney transplant recipients (475 in the first and 560 in the second wave), results were essentially similar except that patients in the second wave were younger (55.6 years versus 58.2 years;P = .002), and crude HR for 28-day mortality from the date of first symptoms was 0.66 (95% CI: 0.47-0.93), whereas the fully adjusted HR was 1.02 (95% CI: 0.70-1.49). CONCLUSION: Among patients on KRT with COVID-19, 28-day mortality rates were lower in the second wave compared with the first wave. However, a greater proportion of patients with minimal symptoms, lead-time bias in dialysis patients, and younger age in kidney transplant recipients possibly explain the lower mortality during the second wave. Any improvement in patient management during the second wave may not be the main reason for lower mortality. (Table Presented).
ABSTRACT
BACKGROUND AND AIMS: Lower antibody responses after SARS-Cov-2 vaccination have been reported in patients with severely impaired kidney function or patients with kidney replacement treatment. We compared humoral responses and reported adverse events of three vaccines (mRNA-1273, BNT162b2 and AZD1222) in kidney transplant recipients (KTRs), dialysis patients, patients with CKD stages G4-G5 and control subjects without kidney disease. METHOD: KTRs, dialysis patients and patients with CKD stages G4-G5 were vaccinated with either mRNA-1273, BNT162b2 or AZD1222 during the Dutch SARSCoV- 2 vaccination program. Control subjects were all vaccinated with mRNA-1273. Blood samples were obtained at 1 month after two vaccinations by home-based finger prick tests and were analysed for the presence of IgG antibodies against the receptorbinding domain of the spike protein of SARS-CoV-2 using the Sanquin anti-SARSCoV- 2 RBD IgG ELISA assay. Primary endpoints were the antibody titer and reported systemic adverse events (AEs) at 1 month after the second vaccination. Multivariate regression analysis was performed on the difference between vaccines with respect to antibody titer and AEs after correction for sex, ethnicity, BMI, eGFR, dialysis vintage, transplantation characteristics and use of immunosuppressive drugs. RESULTS: A total of 2468 KTRs, 480 dialysis patients, 400 patients with CKD stages G4-G5 and 186 control subjects were enrolled. KTRs had lower antibody titers (66 [8-573] BAU/mL) in comparison to dialysis patients [1375 (431-2896) BAU/mL], patients with CKD stages G4-G5 [2097 (828-4077) BAU/mL] and control subjects [3713 (2291-6451) BAU/mL]. mRNA-1273 demonstrated a higher antibody titer compared with BNT162b2 in KTR [72 (9-638) versus 21 (6-128) BAU/mL;P < .001), dialysis patients [1675 (573-3031) versus 636 (216-1416) BAU/mL;P < .001] and patients with CKD stages G4-G5 [2879 (1425-5311) versus 1063 (389-1939) BAU/mL;P < .001). In a similar pattern, mRNA-1273 demonstrated a higher antibody titer compared with AZD1222 (P < .001 in all groups). Multivariate analysis revealed that BNT162b2 and AZD1222 were significantly associated with lower antibody levels compared with mRNA-1273 in all 3 patient groups. BNT162b2 demonstrated less frequently systemic AEs compared with mRNA-1273 in KTRs (12% versus 27%;P < .001), dialysis patients (12% versus 29%;P = .007) and in patients with CKD G4- G5 (18% versus 67%, P < .001). AZD1222 demonstrated less systemic AEs compared with mRNA-1273 only in patients with CKD stages G4-G5 (39% versus 67%;P = .03). Multivariate analysis revealed that BNT162b2 was associated with fewer systemic AEs in only dialysis patients (P = .04) and patients with CKD stages G4-G5 (P = .02). CONCLUSION: mRNA-1273 demonstrated significantly higher antibody levels at 1 month after 2 vaccinations as compared with BNT162b2 and AZD1222 in high-risk patients with kidney disease. BNT162b2 was associated with a fewer systemic AEs in dialysis patients and patients with CKD stages G4-G5, although these AEs were mild and self-limiting. mRNA-1273 may therefore be considered as the preferred SARS-CoV-2 vaccine in high-risk patients with kidney disease. Whether the higher antibody response following vaccination with mRNA-1273 sustains and results in a better protection against COVID-19 is yet to be analysed.
ABSTRACT
BACKGROUND AND AIMS: Kidney transplant recipients (KTRs) are still at risk of fatal COVID-19 disease after SARS-CoV-2 vaccination, even after a third booster vaccination. With the spread of new SARS-CoV-2 variants, great urgency exists for a better understanding of the factors that impact the immune response in these patients. Our aim was to predict nonseroconversion after SARS-CoV-2 vaccination to understand the factors that may disrupt the humoral response in KTRs. METHOD: A multivariable logistic regression model was developed and validated that uses routinely available clinical and laboratory information to predict nonseroconversion after two doses of SARS-CoV-2 mRNA vaccination in KTRs. KTRs were prospectively enrolled to the Dutch REnal patients COVID-19 VACcination (RECOVAC) consortium, specifically to the Immune Response (IR) study with four participating university medical centres in the Netherlands. The discovery cohort consisted of three participating centres (Amsterdam UMC, Radboud UMC Nijmegen and Erasmus MC Rotterdam), and the validation cohort of patients treated in UMC Groningen. A large second validation set from the RECOVAC consortium (LESS-CoV- 2) was used to test a more simplified version of the model without lymphocyte counts. All participants received two doses of the mRNA-1273 COVID-19 vaccine (Moderna) and had no history of SARS-CoV-2 infection. Participants were classified as responder or non-responder based on seroconversion at day 28 following the second vaccination with a threshold for seropositivity based on receiver operator curve analysis set at S1-specific IgG antibody concentration ≥10 BAU/mL. RESULTS: The discovery cohort included 215 KTRs of which 126 responders and 89 non-responders. After backward selection, 6 out of 19 factors remained predictive for nonseroconversion: increased age, lower lymphocyte count, lower estimated glomerular filtration rate (eGFR), shorter time after transplantation, not using steroids and the use of mycophenolate mofetil/mycophenolic acid (MMF/MPA) (Figure 1). The area under the curve (AUC) of the receiver operating characteristics was 0.83 (95% confidence interval 0.78-0.89) in the discovery cohort after adjustment for optimism and 0.84 (0.74-0.94) in external validation of the UMC Groningen cohort (n = 73), and 0.75 (0.72-0.77) in external validation of the LESS-CoV-2 dataset (n = 2484). In addition, MMF/MPA appeared to have a dose-dependent unfavourable association with the S1 IgG antibody titer (Figure 2). CONCLUSION: Six predictors allow for a better understanding of the process of the development of the humoral response in KTRs. These predictors could be applied to individualized patient counseling and treatment strategy during the COVID-19 pandemic and future innovative vaccine trial design for this complex patient group. (Figure Presented).
ABSTRACT
BACKGROUND: COVID-19 is associated with increased morbidity and mortality in patients with chronic kidney disease (CKD) stages G4-G5, on dialysis or after kidney transplantation (kidney replacement therapy, KRT). SARS-CoV-2 vaccine trials do not elucidate if SARS-CoV-2 vaccination is effective in these patients. Vaccination against other viruses is known to be less effective in kidney patients. Our objective is to assess the efficacy and safety of various types of SARS-CoV-2 vaccinations in patients with CKD stages G4-G5 or on KRT. METHODS: In this national prospective observational cohort study we will follow patients with CKD stages G4-G5 or on KRT (n = 12,000) after SARS-CoV-2 vaccination according to the Dutch vaccination program. Blood will be drawn for antibody response measurements at day 28 and month 6 after completion of vaccination. Patient characteristics and outcomes will be extracted from registration data and questionnaires during 2 years of follow-up. Results will be compared with a control group of non-vaccinated patients. The level of antibody response to vaccination will be assessed in subgroups to predict protection against COVID-19 breakthrough infection. RESULTS: The primary endpoint is efficacy of SARS-CoV-2 vaccination determined as the incidence of COVID-19 after vaccination. Secondary endpoints are the antibody based immune response at 28 days after vaccination, the durability of this response at 6 months after vaccination, mortality and (serious) adverse events. CONCLUSION: This study will fulfil the lack of knowledge on efficacy and safety of SARS-CoV-2 vaccination in patients with CKD stages G4-G5 or on KRT. TRIAL REGISTRATION: The study protocol has been registered in clinicaltrials.gov ( NCT04841785 ). Current knowledge about this subject COVID-19 has devastating impact on patients with CKD stages G4-G5, on dialysis or after kidney transplantation. Effective SARS-CoV-2 vaccination is very important in these vulnerable patient groups. Recent studies on vaccination in these patient groups are small short-term studies with surrogate endpoints. Contribution of this study Assessment of incidence and course of COVID-19 after various types of SARS-CoV-2 vaccination during a two-year follow-up period in not only patients on dialysis or kidney transplant recipients, but also in patients with CKD stages G4-G5. Quantitative analysis of antibody response after SARS-CoV-2 vaccination and its relationship with incidence and course of COVID-19 in patients with CKD stages G4-G5, on dialysis or after kidney transplantation compared with a control group. Monitoring of (serious) adverse events and development of anti-HLA antibodies. Impact on practice or policy Publication of the study design contributes to harmonization of SARS-CoV-2 vaccine study methodology in kidney patients at high-risk for severe COVID-19. Data on efficacy of SARS-CoV-2 vaccination in patients with CKD will provide guidance for future vaccination policy.
Subject(s)
COVID-19 Vaccines , Kidney Transplantation , Renal Dialysis , Renal Insufficiency, Chronic/therapy , COVID-19 Vaccines/administration & dosage , Cohort Studies , Humans , Netherlands , Observational Studies as Topic , Prospective Studies , Time FactorsABSTRACT
Background: Kidney transplant patients are at high risk for COVID-19 related mortality. However, limited data are available on longer term clinical, functional and mental outcomes in patients that survive COVID-19. Methods: Data from adult kidney transplant patients that presented with COVID-19 between February 1st, 2020 and January 31st, 2021 were retrieved from the ERACODA database. Data from patients with complete data for vital status, hospitalization and/or ICU admission was used for this analysis. Results: 912 patients were included with a mean age of 56.7 (±13.7) years. 26.4% were not hospitalized, 57.5% hospitalized, and 16.1% hospitalized and ICU admitted. Three-months survival was 82.3% overall and 98.8%, 84.2% and 49.0% resp. in each group. Three-months acute rejection, need for dialysis / CVVH at any time point, and graft failure occurred in the overall group in 1.0%, 2.6% and 1.8% resp., and in 2.1%, 10.6% and 10.6% of ICU admitted patients resp. Of the surviving patients 83.3% had reached their prior functional status within 3 months. Of patients that had not yet reached their prior functional status, it was expected that 79.6% still would do so within the coming year. 94.4% had reached their prior mental status. Of patients that had not yet reached their prior mental status, it was expected that 80% of patients would do so within the coming year. Conclusions: In patients alive at three-months follow-up, graft loss was rare, and most patients had reached their pre-COVID-19 functional and mental status. Clinical, functional, and mental outcomes in kidney transplant recipients three months after being diagnosed with COVID-19. Data of 487 patients were available for analysis of graft function related outcomes. Data of 450 patients were available for functional and mental status outcomes.
ABSTRACT
BACKGROUND AND AIMS: Patients on kidney replacement therapy (KRT) are at high risk of developing severe COVID-19 illness and often require high intensity care and utilisation of hospital resources. During the ongoing pandemic, the optimal care pathway and triage for KRT patients presenting with varying severity of COVID-19 illness is unknown. We studied clinical factors and outcomes associated with admission, readmission and short-term outcomes. METHOD: Data from the European Renal Association COVID-19 Database (ERACODA) was analysed. This database includes granular data on dialysis patients and kidney transplant recipients with COVID-19 from all over Europe. The clinical and laboratory features at first presentation of hospitalized and non-hospitalized patients and those who returned for second presentation were studied. In addition, possible predictors of outcome in those who were not hospitalized at first presentation were identified. RESULTS: Among 1,423 KRT patients (haemodialysis;1017/kidney transplant;406) with COVID-19, 25% (n=355) were not hospitalized at first presentation. Of them, only 10% (n=36), presented for a second time in the hospital. The median interval between the first and second presentation was 5 days (Interquartile interval: 2-7 days). Patients who re-presented had worsening of pulmonary symptoms, a fall in oxygen saturation (97% to 90%), and an increase in C-reactive protein (26 mg/L to 73 mg/L) between their attendances. Patients who re-presented after initial assessment were older (72 vs. 63 years) and initially more often had pulmonary symptoms and abnormalities on lung imaging compared with those who did not present for a second time. The 28-day mortality rate of patients admitted at the second presentation was similar to that of patients admitted at first presentation (26.5% vs. 29.7%, p=0. 61). Among patients who were not hospitalized at first presentation (mortality 6%), age, prior smoking, clinical frailty scale, and shortness of breath at first presentation were identified as predictors of mortality. CONCLUSION: KRT patients with COVID-19 and mild pulmonary abnormalities and no signs of pulmonary insufficiency can be safely returned without hospitalization. These patients should be advised to seek immediate contact when they develop respiratory distress. Our findings provide support for a risk-stratified clinical approach to admissions of KRT patients presenting with COVID-19. The study findings may be valuable for clinical triage and optimising hospital capacity utilisation during the ongoing pandemic.