Evaluation of two rapid antigen tests to detect SARS-CoV-2 in a hospital setting

Successful containment strategies for the SARS-CoV-2 pandemic will depend on reliable diagnostic assays. Point-of-care antigen tests (POCT) may provide an alternative to time-consuming PCR tests to rapidly screen for acute infections on site. Here, we evaluated two SARS-CoV-2 antigen tests: the STANDARD™ F COVID-19 Ag FIA (FIA) and the SARS-CoV-2 Rapid Antigen Test (RAT). For diagnostic assessment, we used a large set of PCR-positive and PCR-negative respiratory swabs from asymptomatic and symptomatic patients and health care workers in the setting of two University Hospitals in Munich, Germany, i.e. emergency rooms, patient care units or employee test centers. For FIA, overall clinical sensitivity and specificity were 45.4% (n = 381) and 97.8% (n = 360), respectively, and for RAT, 50.3% (n = 445) and 97.7% (n = 386), respectively. For primary diagnosis of asymptomatic and symptomatic individuals, diagnostic sensitivities were 60.9% (FIA) (n = 189) and 64.5% (RAT) (n = 256). This questions these tests' utility for the reliable detection of acute SARS-CoV-2-infected individuals, in particular in high-risk settings. We support the proposal that convincing high-quality outcome data on the impact of false-negative and false-positive antigen test results need to be obtained in a POCT setting. Moreover, the efficacy of alternative testing strategies to complement PCR assays must be evaluated by independent laboratories, prior to widespread implementation in national and international test strategies

Altered ubiquitin signaling induces Alzheimer’s disease-like hallmarks in a three-dimensional human neural cell culture model

Abstract Alzheimer’s disease (AD) is characterized by toxic protein accumulation in the brain. Ubiquitination is essential for protein clearance in cells, making altered ubiquitin signaling crucial in AD development. A defective variant, ubiquitin B + 1 (UBB+1), created by a non-hereditary RNA frameshift mutation, is found in all AD patient brains post-mortem. We now detect UBB+1 in human brains during early AD stages. Our study employs a 3D neural culture platform derived from human neural progenitors, demonstrating that UBB+1 alone induces extracellular amyloid-β (Aβ) deposits and insoluble hyperphosphorylated tau aggregates. UBB+1 competes with ubiquitin for binding to the deubiquitinating enzyme UCHL1, leading to elevated levels of amyloid precursor protein (APP), secreted Aβ peptides, and Aβ build-up. Crucially, silencing UBB+1 expression impedes the emergence of AD hallmarks in this model system. Our findings highlight the significance of ubiquitin signalling as a variable contributing to AD pathology and present a nonclinical platform for testing potential therapeutics