Differentiating patients admitted primarily due to coronavirus disease 2019 (COVID-19) from those admitted with incidentally detected severe acute respiratory syndrome corona-virus type 2 (SARS-CoV-2) at hospital admission: A cohort analysis of German hospital records.

OBJECTIVE: The number of hospitalized patients with severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) does not differentiate between patients admitted due to coronavirus disease 2019 (COVID-19) (ie, primary cases) and incidental SARS-CoV-2 infection (ie, incidental cases). We developed an adaptable method to distinguish primary cases from incidental cases upon hospital admission. DESIGN: Retrospective cohort study. SETTING: Data were obtained from 3 German tertiary-care hospitals. PATIENTS: The study included patients of all ages who tested positive for SARS-CoV-2 by a standard quantitative reverse-transcription polymerase chain reaction (RT-PCR) assay upon admission between January and June 2022. METHODS: We present 2 distinct models: (1) a point-of-care model that can be used shortly after admission based on a limited range of parameters and (2) a more extended point-of-care model based on parameters that are available within the first 24-48 hours after admission. We used regression and tree-based classification models with internal and external validation. RESULTS: In total, 1,150 patients were included (mean age, 49.5±28.5 years; 46% female; 40% primary cases). Both point-of-care models showed good discrimination with area under the curve (AUC) values of 0.80 and 0.87, respectively. As main predictors, we used admission diagnosis codes (ICD-10-GM), ward of admission, and for the extended model, we included viral load, need for oxygen, leucocyte count, and C-reactive protein. CONCLUSIONS: We propose 2 predictive algorithms based on routine clinical data that differentiate primary COVID-19 from incidental SARS-CoV-2 infection. These algorithms can provide a precise surveillance tool that can contribute to pandemic preparedness. They can easily be modified to be used in future pandemic, epidemic, and endemic situations all over the world.

Virus variant-specific clinical performance of SARS coronavirus two rapid antigen tests in point-of-care use, from November 2020 to January 2022.

OBJECTIVES: Antigen rapid diagnostic tests (RDTs) for SARS coronavirus 2 (SARS-CoV-2) are quick, widely available, and inexpensive. Consequently, RDTs have been established as an alternative and additional diagnostic strategy to quantitative reverse transcription polymerase chain reaction (RT-qPCR). However, reliable clinical and large-scale performance data specific to a SARS-CoV-2 virus variant of concern (VOC) are limited, especially for the Omicron VOC. The aim of this study was to compare RDT performance among different VOCs. METHODS: This single-centre prospective performance assessment compared RDTs from three manufacturers (NADAL, Panbio, MEDsan) with RT-qPCR including deduced standardized viral load from oropharyngeal swabs for detection of SARS-CoV-2 in a clinical point-of-care setting from November 2020 to January 2022. RESULTS: Among 35 479 RDT/RT-qPCR tandems taken from 26 940 individuals, 164 of the 426 SARS-CoV-2 positive samples tested true positive with an RDT corresponding to an RDT sensitivity of 38.50% (95% CI, 34.00-43.20%), with an overall specificity of 99.67% (95% CI, 99.60-99.72%). RDT sensitivity depended on viral load, with decreasing sensitivity accompanied by descending viral load. VOC-dependent sensitivity assessment showed a sensitivity of 42.86% (95% CI, 32.82-53.52%) for the wild-type SARS-CoV-2, 43.42% (95% CI, 32.86-54.61%) for the Alpha VOC, 37.67% (95% CI, 30.22-45.75%) for the Delta VOC, and 33.67% (95% CI, 25.09-43.49%) for the Omicron VOC. Sensitivity in samples with high viral loads of ≥106 SARS-CoV-2 RNA copies per mL was significantly lower in the Omicron VOC (50.00%; 95% CI, 36.12-63.88%) than in the wild-type SARS-CoV-2 (79.31%; 95% CI, 61.61-90.15%; p 0.015). DISCUSSION: RDT sensitivity for detection of the Omicron VOC is reduced in individuals infected with a high viral load, which curtails the effectiveness of RDTs. This aspect furthert: limits the use of RDTs, although RDTs are still an irreplaceable diagnostic tool for rapid, economic point-of-care and extensive SARS-CoV-2 screening.

Erratum: Influence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccinations on cluster events among patients and staff in a tertiary-care hospital in Germany - CORRIGENDUM.

[This corrects the article DOI: 10.1017/ash.2021.234.].

Influence of severe acute respiratory coronavirus virus 2 (SARS-CoV-2) vaccinations on cluster events among patients and staff in a tertiary-care hospital in Germany.

In total, 20 severe acute respiratory coronavirus virus 2 (SARS-CoV-2) clusters were analyzed in a tertiary-care hospital from the beginning of the pandemic until July 2021. After the second pandemic wave, the number of clusters decreased with increasing vaccination rates and community infections increased again. These findings should motivate healthcare workers to participate in SARS-CoV-2 vaccination campaigns.

Clinical performance evaluation of SARS-CoV-2 rapid antigen testing in point of care usage in comparison to RT-qPCR.

BACKGROUND: Antigen rapid diagnostic tests (RDT) for SARS-CoV-2 are fast, broadly available, and inexpensive. Despite this, reliable clinical performance data from large field studies is sparse. METHODS: In a prospective performance evaluation study, RDT from three manufacturers (NADAL®, Panbio™, MEDsan®, conducted on different samples) were compared to quantitative reverse transcription polymerase chain reaction (RT-qPCR) in 5 068 oropharyngeal swabs for detection of SARS-CoV-2 in a hospital setting. Viral load was derived from standardised RT-qPCR Cycle threshold (Ct) values. The data collection period ranged from November 12, 2020 to February 28, 2021. FINDINGS: The sensitivity of RDT compared to RT-qPCR was 42·57% (95% CI 33·38%-52·31%). The specificity was 99·68% (95% CI 99·48%-99·80%). Sensitivity declined with decreasing viral load from 100% in samples with a deduced viral load of ≥108 SARS-CoV-2 RNA copies per ml to 8·82% in samples with a viral load lower than 104 SARS-CoV-2 RNA copies per ml. No significant differences in sensitivity or specificity could be observed between samples with and without spike protein variant B.1.1.7. The NPV in the study cohort was 98·84%; the PPV in persons with typical COVID-19 symptoms was 97·37%, and 28·57% in persons without or with atypical symptoms. INTERPRETATION: RDT are a reliable method to diagnose SARS-CoV-2 infection in persons with high viral load. RDT are a valuable addition to RT-qPCR testing, as they reliably detect infectious persons with high viral loads before RT-qPCR results are available. FUNDING: German Federal Ministry for Education and Science (BMBF), Free State of Bavaria.

Preliminary evaluation of pre-speech and neurodevelopmental measures in 7-11-week-old infants with isolated oral clefts.

BACKGROUND: The purpose of this research study was to evaluate the earliest markers of vocal functioning and neurological development in infants with isolated oral cleft of the lip and/or palate (iCL/P). METHODS: Participants were recruited through advertisements and clinic visits at a local mid-western university. A total of eight participants (four unaffected and four with iCL/P), ranging in age from 7.29 to 11.57 weeks, were enrolled and completed demographic and pre-speech measures. A subset of six males (four unaffected and two with iCL/P) successfully completed a structural magnetic resonance imaging scan. RESULTS: Patterns of disrupted vocal control and reduced myelinated white matter were found in participants with iCL/P. CONCLUSIONS: The findings of this study provide a foundation from which to build further research on the neuronal development of infants with oral clefts: the need to evaluate measures of cortical development, inclusion of information on anesthesia exposure and airway obstruction, and suggestions for avoiding identified pitfalls/blocks to obtaining data are discussed. IMPACT: Research in children with isolated oral clefts has demonstrated higher rates of learning disorders connected to subtle differences in brain structure. There is no work evaluating the potential impact of exposure to anesthesia on development. This is the first known attempt to evaluate brain structure and function in infants with isolated oral clefts before exposure to anesthesia. Potential trends of early vocal issues and structural brain differences (less myelinated white matter) were identified in infants with isolated oral clefts compared to unaffected controls. Differences in brain structure and function in infants with isolated oral clefts may be present before surgery.

Anisotropic Superfluid Behavior of a Dipolar Bose-Einstein Condensate.

We present transport measurements on a dipolar superfluid using a Bose-Einstein condensate of ^{162}Dy with strong magnetic dipole-dipole interactions. By moving an attractive laser beam through the condensate we observe an anisotropy in superfluid flow. This observation is compatible with an anisotropic critical velocity for the breakdown of dissipationless flow, which, in the spirit of the Landau criterion, can directly be connected to the anisotropy of the underlying dipolar excitation spectrum. In addition, the heating rate above this critical velocity reflects the same anisotropy. Our observations are in excellent agreement with simulations based on the Gross-Pitaevskii equation and highlight the effect of dipolar interactions on macroscopic transport properties, rendering dissipation anisotropic.

Structure-based optimization of aldose reductase inhibitors originating from virtual screening.

Diabetes mellitus is a universal health problem. The World Health Organization (WHO) estimates that 150 million people suffer from diabetes mellitus worldwide in 2005. Long-term complications are a serious problem in the treatment of diabetes, manifesting in macrovascular and microvascular complications. Sorbitol accumulation has been proposed to be an important factor in the development of microvascular complications such as nephropathy, neuropathy, retinopathy or cataract. Catalyzing the NADPH-dependent reduction of glucose to sorbitol, aldose reductase (ALR2) is an important target in the prevention of these complications. The development of novel aldose reductase inhibitors is expected to benefit strongly from a structure-based design approach. A virtual screening based on the ultrahigh-resolution crystal structure of the inhibitor IDD 594 in complex with human ALR2 identified two compounds with IC(50) values in the low micro- to submicromolar range. Based on the known interactions between the ligands and their binding pocket, we simplified the lead structures to give the minimal structural requirements and developed synthetic pathways from commercially available compounds. The newly synthesized compounds were assayed for their inhibition of ALR2, showing inhibitory activities down to the nanomolar range. Crystal structure analysis of the most potent derivative of our series revealed insights into the binding mode of the inhibitors.