Project description: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.
Project description:ObjectiveTo identify barriers and enablers to COVID-19 vaccination in renal transplant recipients who are undecided about vaccination.MethodsAn online survey was distributed to 876 adult kidney transplant recipients at a tertiary referral service, who had not been vaccinated against COVID-19. The survey assessed willingness to be vaccinated, attitudes toward COVID-19 vaccines, and barriers and enablers to proceeding with vaccination.ResultsThe survey response rate was 54% (473/876). Three hundred and forty-six (73.1%) participants planned to receive vaccination (yes group), 105 (22.2%) were undecided, and 22 (4.7%) refused vaccination. The undecided group were younger but were not different in other demographic characteristics to the yes group. The undecided group were less positive toward (34.29% vs. 91.3%, p < .001) and more concerned about (93.3% vs. 25.1%, p < .001) vaccination than the yes group. Their concerns related to vaccine safety (including harm to their transplant), poor efficacy, and a lack of rigorous testing in transplant recipients. Undecided recipients had received less vaccine-specific information from medical specialists than the yes group. Most undecided participants (95.1%) were willing to proceed with vaccination with appropriate supports. The most desired supports were information and a recommendation to proceed with vaccination from their treating transplant specialist and team.Conclusion(s)Concerns about vaccine safety (including harm to transplant), poor vaccine efficacy, and lack of rigorous testing were barriers to vaccine uptake. Most undecided recipients would proceed with vaccination with specific recommendations and vaccine information provided by their transplant specialist/team. These simple interventions can be readily implemented to optimize vaccine uptake.
Project description:Kidney transplant recipients might be at higher risk for severe coronavirus disease 2019 (COVID-19). However, risk factors for relevant outcomes remain uncertain in this population. This is a multicentric kidney transplant cohort including 104 hospitalized patients between March 4 and April 17, 2020. Risk factors for death and acute respiratory distress syndrome (ARDS) were investigated, and clinical and laboratory data were analyzed. The mean age was 60 years. Forty-seven patients (54.8%) developed ARDS. Obesity was associated to ARDS development (OR 2.63; P = .04). Significant age differences were not found among patients developing and not developing ARDS (61.3 vs 57.8 years, P = .16). Seventy-six (73%) patients were discharged, and 28 (27%) died. Death was more common among the elderly (55 and 70.8 years, P < .001) and those with preexisting pulmonary disease (OR 2.89, P = .009). At admission, higher baseline lactate dehydrogenase (257 vs 358 IU/mL, P = .001) or ARDS conferred higher risk of death (HR 2.09, P = .044). In our cohort, ARDS was equally present among young and old kidney recipients. However, the elderly might be at higher risk of death, along with those showing higher baseline LDH at admission.
Project description:BackgroundElderly kidney transplant recipients (KTRs) represent almost one third of the total kidney transplant population. These patients have a very high coronavirus disease 2019 (COVID-19)-related mortality, whereas their response to COVID-19 vaccination is impaired. Finding ways to improve the COVID-19 vaccination response in this vulnerable population is of uttermost importance.MethodsIn the OPTIMIZE trial, we randomly assign elderly KTRs to an immunosuppressive regimen with standard-exposure calcineurin inhibitor (CNI), mycophenolate mofetil, and prednisolone or an adapted regimen with low dose CNI, everolimus, and prednisolone. In this substudy, we measured the humoral response after 2 (N = 32) and 3 (N = 22) COVID-19 mRNA vaccinations and the cellular response (N = 15) after 2 vaccinations.Results. The seroconversion rates of elderly KTRs on a standard immunosuppressive regimen were only 13% and 38% after 2 and 3 vaccinations, respectively, whereas the response rates of KTRs on the everolimus regimen were significantly higher at 56% ( P = 0.009) and 100% ( P = 0.006). Levels of severe acute respiratory syndrome coronaVirus 2 IgG antibodies were significantly higher at both time points in the everolimus group ( P = 0.004 and P < 0.001). There were no differences in cellular response after vaccination.ConclusionsAn immunosuppressive regimen without mycophenolate mofetil, a lower CNI dose, and usage of everolimus is associated with a higher humoral response rate after COVID-19 vaccination in elderly KTRs after transplantation. This encouraging finding should be investigated in larger cohorts, including transplant recipients of all ages.
Project description:BackgroundVaccination of patients with chronic kidney disease (CKD) and kidney transplants (KTs) may achieve a less robust immune response. Understanding such immune responses is crucial for guiding current and future vaccine dosing strategies.MethodsThis prospective, observational study estimated the immunogenicity of humoral and cellular responses of two SARS-CoV-2 vaccines in different patient groups with CKD compared with controls. Secondary outcomes included adverse events after vaccination and the incidence of COVID-19 breakthrough infection, including illness severity.ResultsIn total, 212 patients received ChAdOx1 nCoV-19 (89.62 %) or inactivated vaccines (10.38 %).The antibody response against the S protein was analyzed at T0 (before the first injection), T1 (before the second injection), and T2 (12 weeks after the second injection). Seroconversion occurred in 92.31 % of controls at T2 and in 100 % of patients with CKD, 42.86 % undergoing KT, 80.18 % of hemodialysis (HD), and 0 % of patients undergoing continuous ambulatory peritoneal dialysis (CAPD) at T2 of the ChAdOx1 nCoV-19 vaccine. Neutralizing antibody levels by surrogate virus neutralization test were above the protective level at T2 in each group. The KT group exhibited the lowest neutralizing antibody and T cell response. Blood groups O and vaccine type were associated with good immunological responses. After the first dose, 14 individuals (6.6 out of the total population experienced COVID-19 breakthrough infection.ConclusionImmunity among patients with CKD and HD after vaccination was strong and comparable with that of healthy controls. Our study suggested that a single dose of the vaccine is not efficacious and delays may result in breakthrough infection. Some blood groups and types of vaccine can affect the immune response.