Outcome and effect of vaccination in SARS-CoV-2 Omicron infection in hemodialysis patients: a cohort study.

BACKGROUND: Hemodialysis patients are at high risk of Covid-19, though vaccination has significant efficacy in preventing and reducing the severity of infection. Little information is available on disease severity and vaccine efficacy since the dissemination of the Omicron variant. METHODS: In a multi-center study, during a period of the epidemic driven by the Omicron variant, all hemodialysis patients positive for SARS-CoV-2 were identified. Outcomes were analyzed according to predictor variables including vaccination status. Risk of infection was analyzed using a Cox proportional hazards model. RESULTS: SARS-CoV-2 infection was identified in 1126 patients including 200 (18%) unvaccinated, 56 (5%) post first dose, 433 (38%) post second dose, and 437 (39%) at least 7 days beyond their third dose. The majority of patients had a mild course but 160 (14%) were hospitalized and 28 (2%) died. In regression models adjusted for age and comorbidity, two-dose vaccination was associated with a 39% (95%CI: 2%-62%) reduction in admissions, but third doses provided additional protection, with a 51% (95%CI: 25%-69%) further reduction in admissions. Among 1265 patients at risk at the start of the observation period, SARS-CoV-2 infection was observed in 211 (17%). Two-dose vaccination was associated with a 41% (95%CI: 3%-64%) reduction in the incidence of infection, with no clear additional effect provided by third doses. CONCLUSIONS: These data demonstrate lower incidence of SARS-CoV-2 infection after vaccination in dialysis patients during an Omicron dominant period of the epidemic. Among those developing infection, severe illness was less common with prior vaccination, particularly after third vaccine doses.

Severity of COVID-19 after Vaccination among Hemodialysis Patients: An Observational Cohort Study.

BACKGROUND AND OBJECTIVES: Patients receiving hemodialysis are at high risk from coronavirus disease 2019 (COVID-19) and demonstrate impaired immune responses to vaccines. There have been several descriptions of their immunologic responses to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination, but few studies have described the clinical efficacy of vaccination in patients on hemodialysis. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: In a multicenter observational study of the London hemodialysis population undergoing surveillance PCR testing during the period of vaccine rollout with BNT162b2 and AZD1222, all of those positive for SARS-CoV-2 were identified. Clinical outcomes were analyzed according to predictor variables, including vaccination status, using a mixed effects logistic regression model. Risk of infection was analyzed in a subgroup of the base population using a Cox proportional hazards model with vaccination status as a time-varying covariate. RESULTS: SARS-CoV-2 infection was identified in 1323 patients of different ethnicities (Asian/other, 30%; Black, 38%; and White, 32%), including 1047 (79%) unvaccinated, 86 (7%) after first-dose vaccination, and 190 (14%) after second-dose vaccination. The majority of patients had a mild course; however, 515 (39%) were hospitalized, and 172 (13%) died. Older age, diabetes, and immune suppression were associated with greater illness severity. In regression models adjusted for age, comorbidity, and time period, prior two-dose vaccination was associated with a 75% (95% confidence interval, 56 to 86) lower risk of admission and 88% (95% confidence interval, 70 to 95) fewer deaths compared with unvaccinated patients. No loss of protection was seen in patients over 65 years or with increasing time since vaccination, and no difference was seen between vaccine types. CONCLUSIONS: These data demonstrate a substantially lower risk of severe COVID-19 after vaccination in patients on dialysis who become infected with SARS-CoV-2.

The Characteristics, Dynamics, and the Risk of Death in COVID-19 Positive Dialysis Patients in London, UK.

Background: Patients on dialysis with frequent comorbidities, advanced age, and frailty, who visit treatment facilities frequently, are perhaps more prone to SARS-CoV-2 infection and related death-the risk factors and dynamics of which are unknown. The aim of this study was to investigate the hospital outcomes in patients on dialysis infected with SARS-CoV-2. Methods: Data on 224 patients on hemodialysis between February 29, 2020 and May 15, 2020 with confirmed SARS-CoV-2 were analyzed for outcomes and potential risk factors for death, using a competing risk-regression model assessed by subdistribution hazards ratio (SHR). Results: Crude data analyses suggest an overall case-fatality ratio of 23% (95% CI, 17% to 28%) overall, but that varies across age groups from 11% (95% CI, 0.9% to 9.2%) in patients ≤50 years old and 32% (95% CI, 17% to 48%) in patients >80 years; with 60% of deaths occurring in the first 15 days and 80% within 21 days, indicating a rapid deterioration toward death after admission. Almost 90% of surviving patients were discharged within 28 days. Death was more likely than hospital discharge in patients who were more frail (WHO performance status, 3-4; SHR, 2.16 [95% CI, 1.25 to 3.74]; P=0.006), had ischemic heart disease (SHR, 2.28 [95% CI, 1.32 to 3.94]; P=0.003), cerebrovascular disease (SHR, 2.11 [95% CI, 1.20 to 3.72]; P=0.01), smoking history (SHR, 2.69 [95% CI, 1.33 to 5.45]; P=0.006), patients who were hospitalized (SHR, 10.26 [95% CI, 3.10 to 33.94]; P<0.001), and patients with high CRP (SHR, 1.35 [95% CI, 1.10 to 1.67]) and a high neutrophil:lymphocyte ratio (SHR, 1.03 [95% CI, 1.01 to 1.04], P<0.001). Our data did not support differences in the risk of death associated with sex, ethnicity, dialysis vintage, or other comorbidities. However, comparison with the entire dialysis population attending these hospitals, in which 13% were affected, revealed that patients who were non-White (62% versus 52% in all patients, P=0.001) and those with diabetes (54% versus 22%, P<0.001) were disproportionately affected. Conclusions: This report discusses the outcomes of a large cohort of patients on dialysis. We found SARS-CoV-2 infection affected more patients with diabetes and those who were non-White, with a high case-fatality ratio, which increased significantly with age, frailty, smoking, increasing CRP, and neutrophil:lymphocyte ratio at presentation.

The LIFT trial: study protocol for a double-blind, randomised, placebo-controlled trial of K+-binder Lokelma for maximisation of RAAS inhibition in CKD patients with heart failure.

BACKGROUND: CKD is common in heart failure (HF) and associated with morbidity and mortality, yet life-prolonging medications such as renin-angiotensin-aldosterone inhibitors (RAASi) are underused due to risk of hyperkalaemia. Sodium zirconium cyclosilicate (SZC) is a potassium-binding medication that has been shown to reduce incidence of hyperkalaemia in CKD, non-CKD, and HF populations, which we propose will support maximisation of RAASi therapy. METHODS: We propose a 1:1 randomised, double-blind, placebo-controlled trial in which participants will receive either SZC or placebo. We will up-titrate participants' RAASi therapy while monitoring their serum potassium levels and adjusting their SZC dose if necessary. Participants with CKD and HF will be recruited from CKD and HF clinics at St George's Hospital. The total study period will be 18 months; 130 participants will be enrolled for approximately two months each following screening. Our primary outcome will be the proportion of participants who achieve maximum RAASi dose while maintaining normokalaemia. Secondary outcomes include participants reaching maximum RAASi dose without severe hyperkalaemia; time from randomisation to hyperkalaemia; time from randomisation to severe hyperkalaemia; number of RAASi dose escalations per participant; final doses of RAASi therapy; changes in quality of life score, eGFR, ACR, serum sodium, troponin T; number and duration of hospital admissions; and within-participant change in serum potassium compared to baseline. DISCUSSION: This trial will be the first to examine the use of SZC for the maximisation of RAASi dosing in patients with advanced CKD and HF. We will assess the impact of achieving target RAASi dosing on hospital admission rates and duration of stay, with the hope that optimum RAASi treatment will translate into reduced morbidity and improved QoL. If clinical benefit is demonstrated, we hope that the joint multidisciplinary CKD-HF approach will be expanded. TRIAL REGISTRATION: EudraCT number 2020-002946-18. Registered on 08 June 2020. Online record pending.

Risk of COVID-19 Disease, Dialysis Unit Attributes, and Infection Control Strategy among London In-Center Hemodialysis Patients.

BACKGROUND AND OBJECTIVES: Patients receiving in-center hemodialysis treatment face unique challenges during the coronavirus disease 2019 (COVID-19) pandemic, specifically the need to attend for treatment that prevents self-isolation. Dialysis unit attributes and isolation strategies that might reduce dialysis center COVID-19 infection rates have not been previously examined. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: We explored the role of variables, including community disease burden, dialysis unit attributes (size and layout), and infection control strategies, on rates of COVID-19 among patients receiving in-center hemodialysis in London, United Kingdom, between March 2, 2020 and May 31, 2020. The two outcomes were defined as (1) a positive test for infection or admission with suspected COVID-19 and (2) admission to the hospital with suspected infection. Associations were examined using a discrete time multilevel time-to-event analysis. RESULTS: Data on 5755 patients dialyzing in 51 units were analyzed; 990 (17%) tested positive and 465 (8%) were admitted with suspected COVID-19 between March 2 and May 31, 2020. Outcomes were associated with age, diabetes, local community COVID-19 rates, and dialysis unit size. A greater number of available side rooms and the introduction of mask policies for asymptomatic patients were inversely associated with outcomes. No association was seen with sex, ethnicity, or deprivation indices, nor with any of the different isolation strategies. CONCLUSIONS: Rates of COVID-19 in the in-center hemodialysis population relate to individual factors, underlying community transmission, unit size, and layout.

Systematic Review and Meta-analysis of COVID-19 and Kidney Transplant Recipients, the South West London Kidney Transplant Network Experience.

INTRODUCTION: There is paucity of literature comparing outcomes of kidney transplant patients with COVID-19 to that of dialysis and waitlisted patients. This report describes our data, provides comparative analysis, together with a meta-analysis of published studies, and describes our protocols to restart the transplant program. METHODS: Data were analyzed on kidney transplant, dialysis, and waitlisted patients tested positive for SARS-CoV-2 (nasopharyngeal swab polymerase chain reaction [PCR] test) between March 1, 2020, and June 30, 2020, together with a meta-analysis of 16 studies. RESULTS: Twenty-three of 1494 kidney transplant patients tested positive for SARS-CoV-2 compared with 123 of 1278 hemodialysis patients (1.5% vs. 9.6%, P < 0.001) and 12 of 253 waitlisted patients (1.5% vs. 4.7%, P = 0.002). Nineteen patients required hospital admission, of whom 6 died and 13 developed AKI. The overall case fatality ratio was 26.1% compared with patients on hemodialysis (27.6%, P = 0.99) and waitlisted patients (8.3%, P = 0.38). Within our entire cohort, 0.4% of transplant patients died compared with 0.4% of waitlisted patients and 2.7% of hemodialysis patients. Patients who died were older (alive [median age 71 years] vs. dead [median age 59 years], P = 0.01).In a meta-analysis of 16 studies, including ours, the pooled case fatality ratio was 24% (95% confidence interval [CI] 19%, 28%); AKI proportion in 10 studies was 50% (95% CI 45%, 56%), with some evidence against no heterogeneity between studies (P = 0.02). CONCLUSIONS: From our cohort of transplant patients, a significantly lower proportion of patients contracted COVID-19 compared with waitlisted and dialysis patients. The case fatality ratio was comparable to that of the dialysis cohort and to a pooled case fatality ratio from a meta-analysis of 16 studies. The pooled AKI ratio in the meta-analysis was similar to our results.

COVID-19 infection in kidney transplant recipients.

By 21 March 2020 infections related to the novel coronavirus SARS-CoV-2 had affected people from 177 countries and caused 11,252 reported deaths worldwide. Little is known about risk, presentation and outcomes of SARS-CoV-2 (COVID-19) infection in kidney transplantation recipients, who may be at high-risk due to long-term immunosuppression, comorbidity and residual chronic kidney disease. Whilst COVID-19 is predominantly a respiratory disease, in severe cases it can cause kidney and multi-organ failure. It is unknown if immunocompromised hosts are at higher risk of more severe systemic disease. Therefore, we report on seven cases of COVID-19 in kidney transplant recipients (median age 54 (range 45-69), three females, from a cohort of 2082 managed transplant follow-up patients) over a six-week period in three south London hospitals. Two of seven patients presented within three months of transplantation. Overall, two were managed on an out-patient basis, but the remaining five required hospital admission, four in intensive care units. All patients displayed respiratory symptoms and fever. Other common clinical features included hypoxia, chest crepitation, lymphopenia and high C-reactive protein. Very high D dimer, ferritin and troponin levels occurred in severe cases and likely prognostic. Immunosuppression was modified in six of seven patients. Three patients with severe disease were diabetic. During a three week follow up one patient recovered, and one patient died. Thus, our findings suggest COVID-19 infection in kidney transplant patients may be severe, requiring intensive care admission. The symptoms are predominantly respiratory and associated with fever. Most patients had their immunosuppression reduced and were treated with supportive therapy.