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Background
The impact of the infecting SARS-CoV-2 variant of concern (VOC) and the vaccination status was determined on the magnitude, breadth, and durability of the neutralizing antibody (nAb) profile in a longitudinal multicentre cohort study.
Methods
173 vaccinated and 56 non-vaccinated individuals were enrolled after SARS-CoV-2 Alpha, Delta, or Omicron infection and visited four times within 6 months and nAbs were measured for D614G, Alpha, Delta, BA.1, BA.2, BA.5, BQ.1.1, XBB.1.5 and JN.1.
Findings
Magnitude-breadth-analysis showed enhanced neutralization capacity in vaccinated individuals against multiple VOCs. Longitudinal analysis revealed sustained neutralization magnitude-breadth after antigenically distant Delta or Omicron breakthrough infection (BTI), with triple-vaccinated individuals showing significantly elevated titres and improved breadth. Antigenic mapping and antibody landscaping revealed initial boosting of vaccine-induced WT-specific responses after BTI, a shift in neutralization towards infecting VOCs at peak responses and an immune imprinted bias towards dominating WT immunity in the long-term. Despite that bias, machine-learning models confirmed a sustained shift of the immune-profiles following BTI.
Interpretation
In summary, our longitudinal analysis revealed delayed and short lived nAb shifts towards the infecting VOC, but an immune imprinted bias towards long-term vaccine induced immunity after BTI.
Funding
This work was funded by the Bavarian State Ministry of Science and the Arts for the CoVaKo study and the ForCovid project. The funders had no influence on the study design, data analysis or data interpretation.
Medical oncology
(2008)
Introduction
Whole Exome Sequencing (WES) has emerged as an efficient tool in clinical cancer diagnostics to broaden the scope from panel-based diagnostics to screening of all genes and enabling robust determination of complex biomarkers in a single analysis.
Methods
To assess concordance, six formalin-fixed paraffin-embedded (FFPE) tissue specimens and four commercial reference standards were analyzed by WES as matched tumor-normal DNA at 21 NGS centers in Germany, each employing local wet-lab and bioinformatics investigating somatic and germline variants, copy-number alteration (CNA), and different complex biomarkers. Somatic variant calling was performed in 494 diagnostically relevant cancer genes. In addition, all raw data were re-analyzed with a central bioinformatic pipeline to separate wet- and dry-lab variability.
Results
The mean positive percentage agreement (PPA) of somatic variant calling was 76% and positive predictive value (PPV) 89% compared a consensus list of variants found by at least five centers. Variant filtering was identified as the main cause for divergent variant calls. Adjusting filter criteria and re-analysis increased the PPA to 88% for all and 97% for clinically relevant variants. CNA calls were concordant for 82% of genomic regions. Calls of homologous recombination deficiency (HRD), tumor mutational burden (TMB), and microsatellite instability (MSI) status were concordant for 94%, 93%, and 93% respectively. Variability of CNAs and complex biomarkers did not increase considerably using the central pipeline and was hence attributed to wet-lab differences.
Conclusion
Continuous optimization of bioinformatic workflows and participating in round robin tests are recommend.
Background
In Germany, around 2.250 children and adolescents are diagnosed with cancer each year. Despite generally positive long-term survival rates, many patients must cope with late effects of the disease and its treatment. This highlights the need for a well-structured, long-term approach addressing both physical and mental health issues. Currently, the German healthcare system lacks such comprehensive structures. Our study aims to evaluate the effectiveness of a structured, multidisciplinary long-term approach compared to conventional “treatment as usual” (TAU).
Methods
A prospective, multicenter study with ten pediatric university clinics in Germany will be conducted. The cluster-randomization takes place at the clinic level. Children and adolescents who completed their cancer treatment at least five years ago and their parents will be eligible to participate. While the control group (CG) receives TAU, the intervention group (IG) participates in a structured program. This program includes risk-based medical treatment and psychosocial interventions tailored to each patient’s individual needs within a two-month timeframe. The primary outcome is the improvement of self-efficacy. Secondary outcomes are satisfaction with health care, improvement of health-related quality of life (HRQoL), reduction of mental health problems, and improvement of transition readiness.
Discussion
This approach has the potential to optimize the health care for individuals who survived cancer during childhood or adolescence. It addresses the challenges of overuse, underuse, and misuse of health care resources. By considering both medical and psychosocial factors and promoting increased self-efficacy, independent from parental involvement, it may facilitate a smoother transition to adult medicine and enhance adherence to lifelong aftercare. If proven successful, this approach will contribute to the integration of multidisciplinary strategies into standard healthcare practice.
Trial registration
German Clinical Trials Register DRKS00029269. Registered on December 23, 2022.
Catallaxy-based grid markets
(2005)
An acoustically-driven biochip – impact of flow on the cell-association of targeted drug carriers
(2009)
Histopathological patterns in atypical teratoid/rhabdoid tumors are related to molecular subgroup
(2021)
