The swab site of the upper airways influences the diagnostic sensitivity for the omicron variant of SARS-CoV-2.

The cycle-threshold-value (CT -value) is a quantitative value of the polymerase chain reaction (PCR), which represents the gold standard for the detection of severe acute respiratory syndrome coronavirus 2 (SARS CoV 2). The CT -value can be used to indicate the viral load in swabs of the airways. The collection of a specimen is the only part of the testing process, which is performed manually and carries, therefore, a high potential for increasing measurement variability. The comparison of different PCR results is often difficult since the exact swabbing technique of each test and how do swabs relate in a direct comparison is unknown. For these reasons, the infection course in a patient can be hard infer even after multiple swabs. As the Omicron variant spread from 06/2022 to 08/2022, all common modalities of the upper airway swabs (nasopharyngeal, oropharyngeal, combined naso-oropharyngeal, nasal orifice swabs as well as swabs of the buccal mucosa), which were performed on patients with a suspected infection with SARS CoV 2. RT-PCR was used for SARS CoV 2 RNA detection and the sample comparison was based on the CT -values obtained. Viral loads can vary significantly depending on the swab sites of the upper airways. For the maximum clinical sensitivity, a combined naso-oropharyngeal swab should be considered. In case a single point and single sample measurement is the norm, a nasopharyngeal swab can deliver the highest viral load at the presumed beginning of the infection. Furthermore, the findings of this study can be valuable to correctly interpret results of different PCR with different sampling techniques.

Multicenter Evaluation of a Fully Automated High-Throughput SARS-CoV-2 Antigen Immunoassay.

INTRODUCTION: Molecular testing for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) continues to suffer from delays and shortages. Antigen tests have recently emerged as a viable alternative to detect patients with high viral loads, associated with elevated risk of transmission. While rapid lateral flow tests greatly improved accessibility of SARS-CoV-2 detection in critical areas, their manual nature limits scalability and suitability for large-scale testing schemes. The Elecsys® SARS-CoV-2 Antigen assay allows antigen immunoassays to be carried out on fully automated high-throughput serology platforms. METHODS: A total of 3139 nasopharyngeal and oropharyngeal swabs were collected at 3 different testing sites in Germany. Swab samples were pre-characterized by reverse transcription real-time polymerase chain reaction (RT-qPCR) and consecutively subjected to the antigen immunoassay on either the cobas e 411 or cobas e 801 analyzer. RESULTS: Of the tested respiratory samples, 392 were PCR positive for SARS-CoV-2 RNA. Median concentration was 2.95 × 104 (interquartile range [IQR] 5.1 × 102-3.5 × 106) copies/ml. Overall sensitivity and specificity of the antigen immunoassay were 60.2% (95% confidence interval [CI] 55.2-65.1) and 99.9% (95% CI 99.6-100.0), respectively. A 93.7% (95% CI 89.7-96.5) sensitivity was achieved at a viral RNA concentration ≥ 104 copies/ml (~ cycle threshold [Ct] value < 29.9). CONCLUSION: The Elecsys SARS-CoV-2 Antigen assay reliably detected patient samples with viral loads ≥ 10,000 copies/ml. It thus represents a viable high-throughput alternative for screening of patients or in situations where PCR testing is not readily available.

The Impact of Hyperosmolality on Activation and Differentiation of B Lymphoid Cells.

B lymphocytes, as a central part of adaptive immune responses, have the ability to fight against an almost unlimited numbers of pathogens. Impairment of B cell development, activation and differentiation to antibody secreting plasma cells can lead to malignancy, allergy, autoimmunity and immunodeficiency. However, the impact of environmental factors, such as hyperosmolality or osmotic stress caused by varying salt concentrations in different lymphoid organs, on these processes is not well-understood. Here, we report that B cells respond to osmotic stress in a biphasic manner. Initially, increased osmolality boosted B cell activation and differentiation as shown by an untimely downregulation of Pax5 as well as upregulation of CD138. However, in the second phase, we observed an increase in cell death and impaired plasmablast differentiation. Osmotic stress resulted in impaired class switch to IgG1, inhibition of phosphorylation of p38 mitogen-activated kinase and a delayed NFAT5 response. Overall, these findings demonstrate the importance of microenvironmental hyperosmolality and osmotic stress caused by NaCl for B cell activation and differentiation.

Tissue sodium storage: evidence for kidney-like extrarenal countercurrent systems?

Recent evidence from chemical analysis of tissue electrolyte and water composition has shown that body Na(+) content in experimental animals is not constant, does not always readily equilibrate with water, and cannot be exclusively controlled by the renal blood purification process. Instead, large amounts of Na(+) are stored in the skin and in skeletal muscle. Quantitative non-invasive detection of Na(+) reservoirs with sodium magnetic resonance imaging ((23)NaMRI) suggests that this mysterious Na(+) storage is not only an animal research curiosity but also exists in humans. In clinical studies, tissue Na(+) storage is closely associated with essential hypertension. In animal experiments, modulation of reservoir tissue Na(+) content leads to predictable blood pressure changes. The available evidence thus suggests that the patho(?)-physiological process of Na(+) storage might be of relevance for human health and disease.