ABSTRACT
B.1.1.7 lineage SARS-CoV-2 is more transmissible, leads to greater clinical severity, and results in modest reductions in antibody neutralization. Subgenomic RNA (sgRNA) is produced by discontinuous transcription of the SARS-CoV-2 genome. Applying our tool (periscope) to ARTIC Network Oxford Nanopore Technologies genomic sequencing data from 4400 SARS-CoV-2 positive clinical samples, we show that normalised sgRNA is significantly increased in B.1.1.7 (alpha) infections (n = 879). This increase is seen over the previous dominant lineage in the UK, B.1.177 (n = 943), which is independent of genomic reads, E cycle threshold and days since symptom onset at sampling. A noncanonical sgRNA which could represent ORF9b is found in 98.4% of B.1.1.7 SARS-CoV-2 infections compared with only 13.8% of other lineages, with a 16-fold increase in median sgRNA abundance. We demonstrate that ORF9b protein levels are increased 6-fold in B.1.1.7 compared to a B lineage virus in vitro. We hypothesise that increased ORF9b in B.1.1.7 is a direct consequence of a triple nucleotide mutation in nucleocapsid (28280:GAT > CAT, D3L) creating a transcription regulatory-like sequence complementary to a region 3' of the genomic leader. These findings provide a unique insight into the biology of B.1.1.7 and support monitoring of sgRNA profiles to evaluate emerging potential variants of concern.
Subject(s)
COVID-19 , RNA , COVID-19/diagnosis , COVID-19/genetics , Humans , SARS-CoV-2/geneticsABSTRACT
Background: It is essential to ensure that youth with specific learning disabilities (SLD) receive an appropriate type and amount of vocational rehabilitation (VR) services to facilitate their entrance to employment and career development. Methods: In this study, the chi-squared automatic interaction detector (CHAID) analysis and multivariate logistic regression analysis were used to investigate the relationship among demographic variables, VR services, and employment outcomes for transition-age youth with SLD. Results: Results indicated that age, gender, race, educational level, and cash benefits from the Social Security Administration were significant predictors of employment outcomes for transition-age youth with SLD. After controlling for the effects of demographic variables, job and training related services had significant relationships with employment outcomes. Most notably, job placement, occupational/vocational training, and on-the-job support services had the strongest relationships with competitive employment outcomes. Conclusion: These findings support the effectiveness of job-related services and supported employment for transitionage youth with SLD. Implications for future research and practice in the wake of the COVID-19 pandemic are discussed. (PsycInfo Database Record (c) 2022 APA, all rights reserved)
ABSTRACT
Hospital outbreaks of COVID19 result in considerable mortality and disruption to healthcare services and yet little is known about transmission within this setting. We characterise within hospital transmission by combining viral genomic and epidemiological data using Bayesian modelling amongst 2181 patients and healthcare workers from a large UK NHS Trust. Transmission events were compared between Wave 1 (1st March to 25th J'uly 2020) and Wave 2 (30th November 2020 to 24th January 2021). We show that staff-to-staff transmissions reduced from 31.6% to 12.9% of all infections. Patient-to-patient transmissions increased from 27.1% to 52.1%. 40%-50% of hospital-onset patient cases resulted in onward transmission compared to 4% of community-acquired cases. Control measures introduced during the pandemic likely reduced transmissions between healthcare workers but were insufficient to prevent increasing numbers of patient-to-patient transmissions. As hospital-acquired cases drive most onward transmission, earlier identification of nosocomial cases will be required to break hospital transmission chains.