ABSTRACT
BackgroundModification of vaccination strategies is needed to improve the immune response to SARS-CoV-2 vaccination in kidney transplant recipients (KTRs). MethodsThis multicenter observational study aimed to determine antibody kinetics among 60 seropositive KTRs and analyzed the effects of the third vaccination against SARS-CoV-2 in 174 previously seronegative KTRs. We investigated whether mycophenolate mofetil (MMF) dose reduction by 25-50% prior the third vaccination influences vaccination success. Results18 of 60 (30%) seropositive KTRs became seronegative in the serological assay within six months. Loss of antibodies was predicted by low initial antibody levels ([≤]206.8 BAU/ml), older age, and impaired graft function. A third vaccination in previously seronegative KTRs induced seroconversion in 56 of 174 (32.1%) KTRs with median antibody levels 119 (76-353) BAU/ml and median neutralizing capacity titer of 1:10 (0- 1:40). Multivariate logistic regression revealed that initial antibody levels (OR 1.39, 95% CI 1.09-1.76), graft function (OR 0.05, 95% CI 0.01-0.39), time after transplantation (OR 1.04, 95% CI 1.02-1.07) and MMF trough levels (OR 0.43, 95% CI 0.21-0.88) correlated with seroconversion, p<0.05. After controlling for these confounders, the effect of MMF dose reduction was calculated using propensity score matching. KTRs in the MMF reduction group had significantly lower MMF serum concentrations prior to the third vaccination and were more likely to develop antibody levels [≥]35.2 BAU/ml than their matched KTRs (p=0.02). ConclusionsTemporary reduction in MMF dose might be a promising approach to improve the immune response in KTRs.
ABSTRACT
BackgroundThe SARS-CoV-2 pandemic remains a worldwide challenge. The CRIT-Cov-U pilot study generated a urinary proteomic biomarker consisting of 50 peptides (COV50), which predicted death and disease progression. Following the interim analysis demanded by the German government, the full dataset was analysed to consolidate findings and propose clinical applications. MethodsIn eight European countries, 1012 adults with PCR-confirmed COVID-19 were followed up for death and progression along the 8-point WHO scale. Capillary electrophoresis coupled with mass spectrometry was used for urinary proteomic profiling. Statistical methods included logistic regression, receiver operating curve analysis with comparison of the area under curve (AUC) between nested models. Hospitalisation costs were derived from the care facility corresponding with the Markov chain probability of reaching WHO scores ranging from 3 to 8 and flat-rate hospitalistion costs standardised across countries. FindingsThe entry WHO scores were 1-3, 4-5 and 6 in 445 (44{middle dot}0%), 529 (52{middle dot}3%), and 38 (3{middle dot}8%) patients, of whom 119 died and 271 progressed. The standardised odds ratios associated with COV50 for death were 2{middle dot}44 (95% CI, 2{middle dot}05-2{middle dot}92) unadjusted and 1{middle dot}67 (1{middle dot}34-2{middle dot}07) if adjusted for sex, age, body mass index, comorbidities and baseline WHO score, and 1{middle dot}79 (1{middle dot}60-2{middle dot}01) and 1{middle dot}63 (1{middle dot}40-1{middle dot}90), respectively, for disease progression (p<0{middle dot}0001 for all). The predictive accuracy of optimised COV50 thresholds were 74{middle dot}4% (95% CI, 71{middle dot}6-77{middle dot}1) for mortality (threshold 0{middle dot}47) and 67{middle dot}4% (64{middle dot}1-70{middle dot}3) for disease progression (threshold 0{middle dot}04). On top of covariables and the baseline WHO score, these thresholds improved AUCs from 0{middle dot}835 to 0{middle dot}853 (p=0{middle dot}0331) and from 0{middle dot}697 to 0{middle dot}730 (p=0{middle dot}0008) for death and progression, respectively. Of 196 ambulatory patients, 194 (99{middle dot}0%) did not reach the 0{middle dot}04 threshold. Earlier intervention guided by high-risk COV50 levels should reduce hospital days with cost reductions expressed per 1000 patient-days ranging from M{euro} 1{middle dot}208 (95% percentile interval, 1{middle dot}035-1{middle dot}406) at low risk (COV50 <0{middle dot}04) to M{euro} 4{middle dot}503 (4{middle dot}107-4{middle dot}864) at high risk (COV50 [≥]0{middle dot}04 and age [≥]65 years). InterpretationThe urinary proteomic COV50 marker is accurate in predicting adverse COVID-19 outcomes. Even in mild-to-moderate PCR-confirmed infections (WHO scores 1-5), the 0{middle dot}04 threshold justifies earlier drug treatment, thereby reducing hospitalisation days and costs. FundingGerman Federal Ministry of Health acting upon a decree from the German Federal Parliament.
ABSTRACT
Given the highly variable clinical phenotype of Coronavirus disease 2019 (COVID-19), a deeper analysis of the host genetic contribution to severe COVID-19 is important to improve our understanding of underlying disease mechanisms. Here, we describe an extended GWAS meta-analysis of a well-characterized cohort of 3,260 COVID-19 patients with respiratory failure and 12,483 population controls from Italy, Spain, Norway and Germany/Austria, including stratified analyses based on age, sex and disease severity, as well as targeted analyses of chromosome Y haplotypes, the human leukocyte antigen (HLA) region and the SARS-CoV-2 peptidome. By inversion imputation, we traced a reported association at 17q21.31 to a highly pleiotropic [~]0.9-Mb inversion polymorphism and characterized the potential effects of the inversion in detail. Our data, together with the 5th release of summary statistics from the COVID-19 Host Genetics Initiative, also identified a new locus at 19q13.33, including NAPSA, a gene which is expressed primarily in alveolar cells responsible for gas exchange in the lung.
ABSTRACT
We whole-genome sequenced 55 SARS-CoV-2 isolates from Western Germany and investigated the genetic structure of SARS-CoV-2 outbreaks in the Heinsberg district and Dusseldorf. While the genetic structure of the Heinsberg outbreak indicates a clonal origin, reflective of superspreading dynamics during the carnival season, distinct viral strains are circulating in Dusseldorf, reflecting the citys international links. Limited detection of Heinsberg strains in the Dusseldorf area despite geographical proximity may reflect efficient containment and contact tracing efforts.
