T cells with grafted specificities for surface antigens provide an avenue for rapidly producing immune effector cells with tumor specificity. However, the function of chimeric receptor (chRec) gene-modified T cells is limited by lack of T-cell expansion and persistence. We propose to use varicella zoster virus (VZV)-reactive T cells as host for the chRec because these cells can be expanded both in vitro and in vivo by stimulation of their native receptor during endogenous reexposure to the virus or by administration of VZV vaccine. We obtained human T cells reactive with VZV from the peripheral blood of seropositive donors by stimulation with VZV lysate and evaluated their characteristics after genetic modification with two tumor-specific model chRecs. Cultures dominated by cytolytic CD4 + T cells (VZV-CTL) could be expanded and maintained in vitro. Gene-modified VZV-CTL recognized and lysed tumor targets in a MHC-independent manner while maintaining functional, MHC-restricted interaction with VZV antigen through their native receptor. Thus, chRec-transduced VZV-CTL may provide a source of potent tumor-reactive cells for adoptive immunotherapy of cancer. The availability of a safe and effective VZV vaccine provides the option of repeated in vivo stimulation to maintain high T-cell numbers until the tumor is eliminated. [Cancer Res 2007;67(17):8335-43]
Purpose
To evaluate the accuracy and cost benefit of a rapid molecular point-of-care testing (POCT) device detecting COVID-19 within a traumatological emergency department.
Background
Despite continuous withdrawal of COVID-19 restrictions, hospitals will remain particularly vulnerable to local outbreaks which is reflected by a higher institution-specific basic reproduction rate. Patients admitted to the emergency department with unknown COVID-19 infection status due to a- or oligosymptomatic COVID-19 infection put other patients and health care workers at risk, while fast diagnosis and treatment is necessary. Delayed testing results in additional costs to the health care system.
Methods
From the 8th of April 2021 until 31st of December 2021, all patients admitted to the emergency department were tested with routine RT-PCR and rapid molecular POCT device (Abbott ID NOW™ COVID-19). COVID-19-related additional costs for patients admitted via shock room or emergency department were calculated based on internal cost allocations.
Results
1133 rapid molecular tests resulted in a sensitivity of 83.3% (95% CI 35.9–99.6%), specificity of 99.8% (95% CI 99.4–100%), a positive predictive value of 71.4% (95% CI 29–96.3%) and a negative predictive value of 99.9% (95% CI 99.5–100%) as compared to RT-PCR. Without rapid COVID-19 testing, each emergency department and shock room admission with subsequent surgery showed additional direct costs of 2631.25€, without surgery of 729.01€.
Conclusion
Although rapid molecular COVID-19 testing can initially be more expensive than RT-PCR, subsequent cost savings, improved workflows and workforce protection outweigh this effect by far. The data of this study support the use of a rapid molecular POCT device in a traumatological emergency department.
Determining SARS-CoV-2 immunity is critical to assess COVID-19 risk and the need for prevention and mitigation strategies. We measured SARS-CoV-2 Spike/Nucleocapsid seroprevalence and serum neutralizing activity against Wu01, BA.4/5 and BQ.1.1 in 1,411 individuals who received medical treatment in five emergency departments in North Rhine-Westphalia, Germany. We detected Spike-IgG in 95.6%, Nucleocapsid-IgG in 24.0% and neutralization against Wu01, BA.4/5 and BQ.1.1 in 94.4%, 85.0%, and 73.8% of participants, respectively. Neutralization against BA.4/5 and BQ.1.1 was reduced 5.6- and 23.4-fold compared to Wu01. Accuracy of S-IgG detection for determination of neutralizing activity against BQ.1.1 was reduced substantially. Furthermore, we explored previous vaccinations and infections as most important correlates of improved BQ.1.1 neutralization using multivariable and Bayesian network analyses. Given an adherence to COVID-19 vaccination recommendations of only 67.7% of all participants, we highlight the need for improvement of vaccine-uptake to reduce the COVID-19 risk in upcoming infection-waves with immune evasive variants.
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