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Assessment of T-cell immunity to the COVID-19 coronavirus requires reliable assays and is of great interest, given the uncertain longevity of the antibody response. Some recent reports have used immunodominant spike (S) antigenic peptides and anti-CD28 co-stimulation in varying combinations to assess T-cell immunity to SARS-CoV-2. These assays may cause T-cell hyperstimulation and could overestimate antiviral immunity in chronically immunosuppressed transplant recipients, who are predisposed to infections and vaccination failures. Here, we evaluate CD154-expressing T-cells induced by unselected S antigenic peptides in 204 subjects-103 COVID-19 patients and 101 healthy unexposed subjects. Subjects included 72 transplanted and 130 non-transplanted subjects. S-reactive CD154+T-cells co-express and can thus substitute for IFN{gamma} (n=3). Assay reproducibility in a variety of conditions was acceptable with coefficient of variation of 2-10.6%. S-reactive CD154+T-cell frequencies were a) higher in 42 healthy unexposed transplant recipients who were sampled pre-pandemic, compared with 59 healthy non-transplanted subjects (p=0.02), b) lower in Tr COVID-19 patients compared with healthy transplant patients (p<0.0001), c) lower in Tr patients with severe COVID-19 (p<0.0001), or COVID-19 requiring hospitalization (p<0.05), compared with healthy Tr recipients. S-reactive T-cells were not significantly different between the various COVID-19 disease categories in NT recipients. Among transplant recipients with COVID-19, cytomegalovirus co-infection occurred in 34%; further, CMV-specific T-cells (p<0.001) and incidence of anti-receptor-binding-domain IgG (p=0.011) were lower compared with non-transplanted COVID-19 patients. Healthy unexposed transplant recipients exhibit pre-existing T-cell immunity to SARS-CoV-2. COVID-19 infection leads to impaired T-cell and antibody responses to SARS-CoV-2 and increased risk of CMV co-infection in transplant recipients.
RESUMO
INTRODUCTION: To improve kidney transplant allocation equitability, a new Kidney Allocation System (KAS) was implemented December 4, 2014. The purpose of this study was to determine if the impact of KAS on peri-operative outcomes differed by recipient race/ethnicity. METHODS: This was a time series analysis using data aggregated in monthly intervals from October 2012 through September 2015 using the University HealthSystem Consortium (UHC). This includes national data aggregated at the center level of all US kidney transplant centers that participate in the UHC (416 centers). Segmented regression with interaction terms was used to determine the impact of KAS on outcomes and differences by race/ethnicity. RESULTS: A total of 28,809 deceased donor kidney transplants were included with 25 months of pre-KAS data and 10 months of post-KAS data. After KAS implementation, the estimated transplant rate per month decreased significantly for Caucasians by 17.6 cases per month (p = 0.0001), and increased significantly for AAs by 37.8 (p = 0.0001), Hispanics by 16.3 (p = 0.0001), and other races by 8.2 cases per month (p = 0.0001). Delayed graft function, 7- and 14-day readmissions significantly increased after KAS, which did not differ by race. Hispanics saw a 7.7% decrease in ICU admissions after KAS, which differed as compared to other racial/ethnic cohorts (p = 0.0026). Costs of kidney transplantation increased significantly after KAS in all groups except Hispanics. Mortality, length of stay, in-hospital complications, and 30-day readmissions were not significantly impacted by KAS, also not differing by race/ethnicity. CONCLUSION: KAS had substantial impact on transplant rates by race/ethnicity. KAS also led to increased costs, readmissions, and delayed graft function (DGF) across all racial/ethnic groups. The impact of KAS on ICU cases solely within Hispanics requires further investigation into potential etiologies.
