Performance of antigen testing for diagnosis of COVID-19: a direct comparison of a lateral flow device to nucleic acid amplification based tests.

OBJECTIVES: The gold standard for diagnosing an infection with SARS-CoV-2 is detection of viral RNA by nucleic acid amplification techniques. Test capacities, however, are limited. Therefore, numerous easy-to-use rapid antigen tests based on lateral flow technology have been developed. Manufacturer-reported performance data seem convincing, but real-world data are missing. METHODS: We retrospectively analysed all prospectively collected antigen tests results performed between 23.06.2020 and 26.11.2020, generated by non-laboratory personnel at the point-of-care from oro- or nasopharyngeal swab samples at the University Hospital Augsburg and compared them to concomitantly (within 24 h.) generated results from molecular tests. RESULTS: For a total of 3630 antigen tests, 3110 NAAT results were available. Overall, sensitivity, specificity, NPV and PPV of antigen testing were 59.4%, 99.0%, 98.7% and 64.8%, respectively. Sensitivity and PPV were lower in asymptomatic patients (47.6% and 44.4%, respectively) and only slightly higher in patients with clinical symptoms (66.7% and 85.0%, respectively). Some samples with very low Ct-values (minimum Ct 13) were not detected by antigen testing. 31 false positive results occurred. ROC curve analysis showed that reducing the COI cut-off from 1, as suggested by the manufacturer, to 0.9 is optimal, albeit with an AUC of only 0.66. CONCLUSION: In real life, performance of lateral-flow-based antigen tests are well below the manufacturer's specifications, irrespective of patient's symptoms. Their use for detection of individual patients infected with SARS-CoV2 should be discouraged. This does not preclude their usefulness in large-scale screening programs to reduce transmission events on a population-wide scale.

Relative value of normalized sonographic in vitro analysis of arteriosclerotic plaques of internal carotid artery.

BACKGROUND AND PURPOSE: A close correlation between B-mode sonography and the histopathology and surface structure of plaque is rarely seen in vivo with high-grade stenoses of the extracranial carotid artery. The goal of this study was to determine whether normalized gray scale analysis and surface analysis of the plaque are capable of characterizing the attributes correctly. METHODS: Optimized B-mode images of 107 carotid endarterectomy specimens were captured, and the gray scale median (GSM) was calculated. The specimens were classified histologically into 3 groups: (1) calcium-rich hard plaques, (2) lipid-rich soft plaques, and (3) combined plaques. The surfaces of the plaques were classified as smooth or rough on the basis of standardized reference samples. The endoluminal surface was digitally documented in vitro by videoendoscopy and again classified into the same categories. All stages of the investigation were performed by 2 observers at 2 different times. RESULTS: Evaluation of the GSM showed close interobserver and intraobserver correlation (P<0.01, R>0.8). However, there was only 46% agreement between the GSM and the histopathological findings. In both in vitro angioscopy (kappa=0.936, P<0.001) and sonographic evaluation (kappa=0.842, P<0.001), there was a high correlation between the observers with regard to the evaluable specimens. In 73%, agreement was observed between the sonographic image and angioscopy. CONCLUSIONS: Normalized gray scale analysis and evaluation of the plaque surface in an in vitro study make possible observer-independent evaluation. The composition of the plaque cannot be visualized with sufficient accuracy by sonographic GSM analysis. This also applies to the correlation between sonography and actual surface composition of the plaque.

Ultrasonographic analysis of arteriosclerotic plaques in the internal carotid artery.

OBJECTIVES: The aim of this study was to investigate whether ultrasonography can characterise plaque morphology and surfaces independent of the observer. METHODS: Computer-assisted image analysis of the grey scales of B-mode scans from 15 patients with stenoses of the internal carotid artery was performed and compared with the histopathological reports. In vitro angioscopy, was used to visualise the plaque surfaces of the thromboendarterectomy specimens. RESULT: Assessment of the internal plaque structure by ultrasound showed close agreement between the two observers (P<0.01) without correlation with the histopathological results. Ultrasonography was able to characterise the plaque surfaces in 93% of cases. CONCLUSION: This investigation showed that standardised computer-assisted analysis of the internal plaque structure correlates less closely than histological investigation, but agrees closely with the surface structure of the plaque. The exclusive use of digital image processing and standardisation of the investigative technique are expected to provide even better results.

Association of a TNFbeta gene polymorphism with complications after major abdominal operations.

In injured patients, it has been shown that a polymorphism of the tumor necrosis factor-beta (TNFbeta) gene is related to the development of sepsis. We investigated the relation of TNFbeta gene polymorphism with the development of severe complications after elective major abdominal operations, and with production of TNFalpha perioperatively. In the present investigation, the Ncol polymorphism was studied in genomic DNA isolated from the blood of 172 patients. Preoperatively and postoperatively, lipopolysaccharide (LPS)-stimulated production of TNFalpha in the patients' whole blood was tested in vitro. Genotypes and TNFalpha production were related to the occurrence of severe complications. Postoperatively, 15% (n = 26) of the patients developed severe complications. The overall mortality was 2% (n = 3). The homozygous TNFB2 genotype was found in 54% of the patients, the homozygous TNFB1 genotype was found in 14% of the patients, and the heterozygous genotype was found in 32% of the patients. In patients with complications, the B2B2 genotype was much more frequent (21/26, 81%) than in those without complications (72/146, 49%; P < 0.003). The development of complications was associated with a lower capacity to produce TNFalpha 3 and 7 days after the operation. In patients without complications, the TNFbeta polymorphism was not related to different levels of TNFalpha production. These data indicate an association between TNFbeta polymorphism and postoperative complications and they suggest the B2/B2 genotype as a high risk factor for the development of sepsis after elective operative trauma.

Effect of abdominal infections on peritoneal and systemic production of interleukin 6 and monocyte chemoattractant protein-1.

The aim of the study was to compare peritoneal and systemic production of interleukin 6 (IL-6) and monocyte chemoattractant protein-1 (MCP-1) in uninfected patients and in patients with peritonitis. Peritoneum was excised at laparotomy for acute peritonitis (n = 22) or noninfectious reasons (n = 61), and was incubated with or without lipopolysaccharide (LPS). Mediator concentrations in the culture-supernatants, in the patients' serum, and in plasmasupernatants of LPS-stimulated whole blood were related to outcome. Spontaneous production of IL-6 by the peritoneum was increased in infected patients compared with uninfected patients. In contrast to IL-6, LPS-stimulated production of MCP-1 was significantly less in infected patients. Serum concentrations of both mediators were higher in infected patients and the highest concentrations of MCP-1 were in patients who died. LPS-stimulated production of IL-6 in whole blood was least, whereas that of MCP-1 was greatest in infected patients who died. These contrasting results for local and systemic production of mediators illustrate the compartmentalized immune response to intra-abdominal infection.