A Safety and Efficacy Study of Dazodalibep in Participants With Sjögren's Syndrome (SS) With Moderate-to-Severe Symptom State

Determining the role and responsibilities of the community epilepsy nurse in the management of epilepsy.

AIMS AND OBJECTIVES: The aim of this study is to enhance the understanding of the core elements and influencing factors on the community-based epilepsy nurse's role and responsibilities. BACKGROUND: Internationally, epilepsy nurse specialists play a key role in providing person-centred care and management of epilepsy but there is a gap in understanding of their role in the community. DESIGN: A national three-stage, mixed-method study was conducted. METHODS: One-on-one, in-depth semi-structured qualitative interviews were conducted online with 12 community-based epilepsy nurses (Stage 1); retrospective analysis of data collected from the National Epilepsy Line, a nurse-led community helpline (Stage 2); and focus group conducted with four epilepsy nurses, to delve further into emerging findings (Stage 3). A thematic analysis was conducted in Stages 1 and 3, and a descriptive statistical analysis of Stage 2 data. Consolidated Criteria for Reporting Qualitative studies checklist was followed for reporting. RESULTS: Three key themes emerged: (1) The epilepsy nurse career trajectory highlighted a lack of standardised qualifications, competencies, and career opportunities. (2) The key components of the epilepsy nurse role explored role diversity, responsibilities, and models of practice in the management of living with epilepsy, and experiences navigating complex fragmented systems and practices. (3) Shifting work practices detailed the adapting work practices, impacted by changing service demands, including COVID-19 pandemic experiences, role boundaries, funding, and resource availability. CONCLUSION: Community epilepsy nurses play a pivotal role in providing holistic, person-centred epilepsy management They contribute to identifying and addressing service gaps through innovating and implementing change in service design and delivery. RELEVANCE TO CLINICAL PRACTICE: Epilepsy nurses' person-centred approach to epilepsy management is influenced by the limited investment in epilepsy-specific integrated care initiatives, and their perceived value is impacted by the lack of national standardisation of their role and scope of practice. NO PATIENT OR PUBLIC CONTRIBUTION: Only epilepsy nurses' perspectives were sought.

A Quality Improvement Innovation for Reproductive Health Planning in the Time of COVID.

OBJECTIVES: To see if an outreach approach with telehealth is feasible and acceptable to patients to talk about their reproductive health; and as a secondary outcome, capture data on time spent on the visit and what kind of information was discussed. METHODS: A registry was created from three family physicians' panels of all adult patients with anticipated ability to become pregnant ages 18-45 who had not had a documented reproductive health discussion in the previous 6 months. Using that registry, outreach was performed to schedule a telehealth visit to discuss their reproductive health with their primary care provider. The visit was standardized using the One Key Question approach. For patients who agreed to participate in the research, the patient completed a survey about their experience. The provider also completed a survey on the time spent and the issues addressed. RESULTS: Two hundred and six patients were called. Ninety patients (44%) could not be reached. Of the remaining patients, 34 scheduled either a telehealth or in-person visit and 7 also agreed to participate in the survey. New information was uncovered in the visit in 86% of participants. The most common need uncovered during the visit was unrelated medical needs (71%), followed by preconception health education/advice (43%) and contraception needs/counseling (29%). Most participants found the telehealth visit valuable. CONCLUSIONS: An outreach methodology can uncover unmet health needs, both reproductive and otherwise. We found that people who had the visit often needed something, but a majority of patients declined the visit saying that they did not think they needed it. It is possible that patients are not aware of the value of reproductive health discussions, and therefore clinicians need to take every opportunity to have these discussions whenever possible, whether through outreach or inreach (during already scheduled visits).

Changes in Sars-Cov-2 Antibody Prevalence in Primary and Secondary Schools Students during the Emergence of the Omicron Variant: The Uk Schools Infection Surveys

Intro: Children and Young people were the last group in England be offered COVID-19 vaccination (from September 2021), thus were the largest susceptible group when SARS-CoV-2 Omicron variants emerged. We monitored vaccine and naturally-derived antibodies in schools between November 2021 and March 2022. Method(s): We conducted three large surveys (November 2021, January and March 2022) in a nationally representative random sample of primary and secondary schools, stratified by regions. Oral fluid samples were tested for IgG antibodies against SARS-CoV-2 nucleocapsid (anti-NP) and spike (anti-S1) proteins using novel validated ELISAs;vaccines used in England elicit anti-S1 antibodies only. We calculated weighted prevalences for each survey, and used multilevel logistic regression to investigate associations with socio-demographic factors. Finding(s): Overall 11311 students contributed 22478 biological samples (respectively 4840, 7549 and 10089 in rounds 1, 2 and 3, with similar socio- demographic characteristics). In 4-11 year olds, not eligible for vaccination, anti- S1 and anti-NP antibody prevalences were 31.3% and 26.6%, 46.2% and 43.8%, and 53.4% and 58.7% respectively over the three rounds. The corresponding estimates in 12 to 18 year olds) were 70.7% and 34.6%, 85.6% and 45.9%, 89.0 and 53.9%. In November 2021 (before Omicron dominance), higher anti-S1 antibody positivity was associated with older age and Black ethnicity, and non- eligibility for free school meals in 4-11 year olds. In 12-18 years it was associated with non-eligibility for free school meals. In March 2022 when Omicron dominated, these associations remained, together with urban location in 4-11 years old. Conclusion(s): The steep increase in 4-11 year olds in both sets of antibodies reflected the emergence and spread of highly infectious Omicron variants whilst high and increasing anti-S1 prevalence in secondary students was consistent with greater vaccine uptake. Socioeconomically deprived 12-18 year olds had lower odds of anti-S1, suggesting lower vaccine uptake or access.Copyright © 2023

Exposure Outcomes in Fully Vaccinated Healthcare Personnel with Known SARS-CoV-2 Exposure-Minnesota, January-August 2021.

Healthcare personnel (HCP) are at potential risk for SARS-CoV-2 infection in occupational and non-occupational settings, even when fully vaccinated. This risk has increased during Delta variant circulation. SARS-CoV-2 testing of fully vaccinated HCP working in the 14 days after exposure is important to prevent virus introduction into healthcare settings.

Typing myalgic encephalomyelitis by infection at onset: A DecodeME study

Background: People with myalgic encephalomyelitis / chronic fatigue syndrome (ME/CFS) daily experience core symptoms of post-exertional malaise, unrefreshing sleep, and cognitive impairment or brain fog. Despite numbering 0.2-0.4% of the population, no laboratory test is available for their diagnosis, no effective therapy exists for their treatment, and no scientific breakthrough regarding their pathogenesis has been made. It remains unknown, despite decades of small-scale studies, whether individuals experience different types of ME/CFS separated by onset-type, sex or age. Methods: : DecodeME is a large population-based study of ME/CFS that recruited 17,074 participants in the first 3 months following full launch. Their detailed questionnaire responses provided an unparalleled opportunity to investigate illness severity, onset, course and duration. Results: : The well-established sex-bias among ME/CFS patients is evident in the initial DecodeME cohort: 83.5% of participants were females. What was not known previously was that females' comorbidities and symptoms tend to be more numerous than males'. Moreover, being female, being older and being over 10 years from ME/CFS onset are significantly associated with greater severity. Five different ME/CFS onset types were examined in the self-reported data: those with ME/CFS onset (i) after glandular fever (infectious mononucleosis);(ii) after COVID-19 infection;(iii) after other infections;(iv) without an identified infectious onset;and, (v) where the occurrence of an infection at or preceding onset is not known. Conclusions: : This revealed that people with a ME/CFS diagnosis are not a homogeneous group, as clear differences exist in symptomatology and comorbidity.

Precision medicines in practice: the connection between CFTR modulators and deranged liver enzymes

Background and AimFor most of the 83 years since acknowledging cystic fibrosis (CF) as a separate disease entity, treatment has primarily focused on symptomatic relief.1 Following the discovery of the CFTR gene, efforts have been made to produce therapies to target the underlying dysfunctions caused by CFTR mutations.2 Moderate transaminase elevations are commonly observed in CF patients. Severe transaminase elevations have been observed in patients taking CFTR modulators in clinical trials with the initial STRIVE trial revealing that treatment discontinuation was commonly due to an increase in hepatic enzymes.3 Consequently, liver function test (LFTs) monitoring is recommended for all patients before commencing therapy, every three months for the first year and annually thereafter. This audit aims to assess the compliance of LFT monitoring in clinical practice for paediatric patients initiated on CFTR modulators, evaluate the incidence of liver-related adverse effects, and examine trends between the CFTR modulator used and the clinical significance of LFT derangements, and determine if there are any sex-related correlations.MethodsPatient data, including date and age on treatment initiation, gender, LFT results at baseline (AST, ALT, ALP, GGT and total bilirubin), first derangement since initiation and monitoring frequency were extracted from the clinical system Meditech®, pseudonymised and analysed. There were 91 records of patients being treated with a CFTR modulator. Some patients were on more than one CFTR modulator as treatment can be switched if eligible. For the purpose of the audit after consultation with the local CF clinical team, a two-month deviation outside of the recommended monitoring frequency was considered non-compliant. LFT derangements were classified as clinically significant if the result was higher than 3 times the upper limit of normal (ULN).ResultsOur study found that most patients (50/91 – 54.9%) on CFTR modulators in the tertiary centre did not have their LFTs monitored following the recommended guidelines. A statistically significant increase in LFT abnormalities from pre- to post- intervention with a CFTR modulator was observed (p=0.015). Kaftrio®/Kalydeco® (3/20 – 15%) and Orkambi® (1/29 – 3.4%) were the only CFTR modulators that led to patients developing clinically significant derangements (>3x ULN). Additionally, a greater proportion of females (24/51 – 47.1%) than males (15/40 – 37.5%) had abnormal LFTs within the tertiary centre contrary to previous epidemiological studies where males have been documented to have a greater risk of abnormal LFTs. However, the strength of this association was negligible (φ =0.096, p=0.360).ConclusionIn conclusion, the tertiary centre's compliance with LFT monitoring guidelines for patients initiated on CFTR modulators was substandard. Most records of treatment initiation occurred during COVID-19, which impacted monitoring as many hospitals suspended routine clinical work to limit the spread of the infection in high-risk groups. Time constraints limited the audit during the data extraction period;therefore, results should be interpreted cautiously. In the absence of the COVID-19 pandemic a re-audit process should include patient lifestyle data and consider other medication regimens that could potentially alter LFTs. Introducing a blood clerk would enable the CF unit to monitor LFT changes more efficiently.ReferencesGuimbellot J, Taylor-Cousar JL. Combination CFTR modulator therapy in children and adults with cystic fibrosis. The Lancet Respiratory Medicine 2021;9:677–679.Lopes-Pacheco M. CFTR Modulators: The Changing Face of Cystic Fibrosis in the Era of Precision Medicine. Frontiers of Pharmacology 2020;10:1662.Gavioli EM, Guardado N, Haniff F, et al. A current review of the safety of cystic fibrosis transmembrane conductance regulator modulators. Journal of Clinical Pharmacy and Therapeutics 2021;46:286–294.

Governing in the time of Covid-19: how board meetings went online and the implications of this for considering the role of the governing board

The response to the COVID-19 pandemic in 2020 necessitated changes in the working practices of many organisations such that online meetings suddenly became the norm. Governing board meetings were no exception. However, little is known about the impact of online meetings on the work of boards. Here we draw on empirical evidence from observations of in-person and online board meetings in eight colleges of further education across the UK to address the question: in what ways do governing board meetings differ in online and in-person contexts? From this we consider what this tells us about the role of the board in the life of the organisation. We conclude that social gathering, which emphasises the importance of place, is of central importance in the work of the board.

Post-COVID-19 condition and persisting symptoms in English schoolchildren: repeated surveys to March 2022.

BACKGROUND: Both post-COVID-19 condition (long COVID) and the presence of persisting symptoms that do not meet formal definitions of post-COVID-19-condition may adversely affect quality of life and function. However, their prevalence among children and young people in England is unclear. METHODS: We used data from repeated surveys in a large cohort of English schoolchildren from the COVID-19 Schools Infection Survey (SIS) for the school year 2021/22 to describe the weighted prevalence of post-COVID-19-condition and compare persisting symptoms between individuals with a positive SARS-CoV-2 test and those with neither a positive test history nor suspected infection. RESULTS: Among 7797 children from 173 schools, 1.8% of primary school pupils (aged 4 to 11 years), 4.5% of secondary school pupils in years 7-11 (aged 11 to 16 years) and 6.9% of those in years 12-13 (aged 16 to 18 years) met a definition of post-COVID-19 condition in March 2022. Specific persisting symptoms such as anxiety or difficulty concentrating were frequently reported regardless of prior infection status and increased with age: 48.0% of primary school pupils, 52.9% of secondary school pupils in years 7-11 and 79.5% in years 12-13 reporting at least one symptom lasting more than 12 weeks. Persisting loss of smell and taste, cardiovascular and some systemic symptoms were more frequently reported by those with a previous positive test. CONCLUSIONS: We showed that ongoing symptoms were frequently reported by English schoolchildren regardless of SARS-CoV-2 test results and some specific symptoms such as loss of smell and taste were more prevalent in those with a positive test history. Our study emphasises the wide-ranging impacts of the COVID-19 pandemic on the health and wellbeing of children and young people.

Implementation of COVID-19 Preventive Measures and Staff Well-Being in a Sample of English Schools 2020-2021.

BACKGROUND: We examined fidelity and feasibility of implementation of COVID-19 preventive measures in schools, and explored associations between adherence to these measures and staff well-being, to inform policy on sustainable implementation and staff wellbeing. METHODS: Surveys were conducted across 128 schools in England with 107 headteachers and 2698 staff-members with reference to autumn term 2020, examining school-level implementation of preventive measures, adherence, and teacher burnout (response rates for headteacher and staff surveys were 84% and 59%, respectively). RESULTS: The median number of measures implemented in primary and secondary schools was 33 (range 23-41), and 32 (range 22-40), respectively; most measures presented challenges. No differences were found regarding number of measures implemented by school-level socio-economic disadvantage. High adherence was reported for staff wearing face-coverings, staff regularly washing their hands, (secondary only) desks facing forwards, and (primary only) increased cleaning of surfaces and student hand-washing. Adherence to most measures was reported as higher in primary than secondary schools. Over half of school leaders and 42% (517/1234) of other teaching staff suffered from high emotional exhaustion. Higher teacher-reported school-wide adherence with measures was consistently associated with lower burnout for leaders and other teaching staff. CONCLUSIONS: Findings indicate a tremendous effort in implementing preventive measures and an urgent need to support investments in improving teacher wellbeing.

DecodeME: community recruitment for a large genetics study of myalgic encephalomyelitis / chronic fatigue syndrome.

BACKGROUND: Myalgic encephalomyelitis / chronic fatigue syndrome (ME/CFS) is a common, long-term condition characterised by post-exertional malaise, often with fatigue that is not significantly relieved by rest. ME/CFS has no confirmed diagnostic test or effective treatment and we lack knowledge of its causes. Identification of genes and cellular processes whose disruption adds to ME/CFS risk is a necessary first step towards development of effective therapy. METHODS: Here we describe DecodeME, an ongoing study co-produced by people with lived experience of ME/CFS and scientists. Together we designed the study and obtained funding and are now recruiting up to 25,000 people in the UK with a clinical diagnosis of ME/CFS. Those eligible for the study are at least 16 years old, pass international study criteria, and lack any alternative diagnoses that can result in chronic fatigue. These will include 5,000 people whose ME/CFS diagnosis was a consequence of SARS-CoV-2 infection. Questionnaires are completed online or on paper. Participants' saliva DNA samples are acquired by post, which improves participation by more severely-affected individuals. Digital marketing and social media approaches resulted in 29,000 people with ME/CFS in the UK pre-registering their interest in participating. We will perform a genome-wide association study, comparing participants' genotypes with those from UK Biobank as controls. This should generate hypotheses regarding the genes, mechanisms and cell types contributing to ME/CFS disease aetiology. DISCUSSION: The DecodeME study has been reviewed and given a favourable opinion by the North West - Liverpool Central Research Ethics Committee (21/NW/0169). Relevant documents will be available online ( www.decodeme.org.uk ). Genetic data will be disseminated as associated variants and genomic intervals, and as summary statistics. Results will be reported on the DecodeME website and via open access publications.

Antibody Persistence After Primary SARS-CoV-2 Infection and Protection Against Future Variants Including Omicron in Adolescents: National, Prospective Cohort Study.

BACKGROUND: Antibodies are a measure of immunity after primary infection, which may help protect against further SARS-CoV-2 infections. They may also provide some cross-protection against SARS-CoV-2 variants. There are limited data on antibody persistence and, especially, cross-reactivity against different SARS-CoV-2 variants after primary infection in children. METHODS: We initiated enhanced surveillance in 18 secondary schools to monitor SARS-CoV-2 infection and transmission in September 2020. Students and Staff provided longitudinal blood samples to test for variant-specific SARS-CoV-2 antibodies using in-house receptor binding domain assays. We recruited 1189 students and 1020 staff; 160 (97 students, 63 staff) were SARS-CoV-2 nucleocapsid-antibody positive at baseline and had sufficient serum for further analysis. RESULTS: Most participants developed sustained antibodies against their infecting [wild-type (WT)] strain as well as cross-reactive antibodies against the Alpha, Beta and Delta variants but at lower titers than WT. Staff had significantly lower antibodies titers against WT as cross-reactive antibodies against the Alpha, Beta and Delta variants than students (all P < 0.01). In participants with sufficient sera, only 2.3% (1/43) students and 17.2% (5/29) staff had cross-reactive antibodies against the Omicron variant; they also had higher antibody titers against WT (3042.5; 95% confidence interval: 769.0-12,036.2) than those who did not have cross-reactive antibodies against the Omicron variant (680.7; 534.2-867.4). CONCLUSIONS: We found very high rates of antibody persistence after primary infection with WT in students and staff. Infection with WT induced cross-reactive antibodies against Alpha, Beta and Delta variants, but not Omicron. Primary infection with WT may not be cross-protective against the Omicron variant.

National and regional prevalence of SARS-CoV-2 antibodies in primary and secondary school children in England: the School Infection Survey, a national open cohort study, November 2021SARS-CoV-2 antibody prevalence in school children.

BACKGROUND: SARS-CoV-2 infection rates are likely to be underestimated in children because of asymptomatic or mild infections. We aim to estimate national and regional prevalence of SARS-CoV-2 antibodies in primary (4-11 years old) and secondary (11-18 years old) school children between 10 November and 10 December 2021. METHODS: Cross-sectional surveillance in England using two-stage sampling, firstly stratifying into regions and selecting local authorities, then selecting schools according to a stratified sample within selected local authorities. Participants were sampled using a novel oral fluid-validated assay for SARS-CoV-2 spike and nucleocapsid IgG antibodies. RESULTS: 4980 students from 117 state-funded schools (2706 from 83 primary schools, 2274 from 34 secondary schools) provided a valid sample. After weighting for age, sex, and ethnicity, and adjusting for assay accuracy, the national prevalence of SARS-CoV-2 antibodies in primary school students, who were all unvaccinated, was 40.1% (95% CI 37.3-43.0). Antibody prevalence increased with age (p < 0.001) and was higher in urban than rural schools (p = 0.01). In secondary school students, the adjusted, weighted national prevalence of SARS-CoV-2 antibodies was 82.4% (95% CI 79.5-85.1); including 71.5% (95% CI 65.7-76.8) in unvaccinated and 97.5% (95% CI 96.1-98.5) in vaccinated students. Antibody prevalence increased with age (p < 0.001), and was not significantly different in urban versus rural students (p = 0.1). CONCLUSIONS: In November 2021, using a validated oral fluid assay, national SARS-CoV-2 seroprevalence was estimated to be 40.1% in primary school students and 82.4% in secondary school students. In unvaccinated children, this was approximately threefold higher than confirmed infections highlighting the importance of seroprevalence studies to estimate prior exposure. DATA AVAILABILITY: Deidentified study data are available for access by accredited researchers in the ONS Secure Research Service (SRS) for accredited research purposes under part 5, chapter 5 of the Digital Economy Act 2017. For further information about accreditation, contact Research.support@ons.gov.uk or visit the SRS website.

Association of Spike-Specific T Cells With Relative Protection From Subsequent SARS-CoV-2 Omicron Infection in Young Children.

This cohort study investigates the risk of SARS-CoV-2 reinfection among young children with and without spike-specific T-cell responses.

A LEGAL HISTORY OF LEGAL HISTORY IN ENGLAND AND WALES

This article explores the development of the study of legal history as a subject in the law schools of England and Wales. It outlines changes in university education more generally, and in legal scholarship in particular and how those changes impact the particular subject under study. Drawing on empirical studies and personal reflections relating to past experience it concludes by speculating on potential different outcomes, both positive and negative, which may emerge when the universities of England and Wales emerge from the uncertainty of the COVID-19 pandemic, during which the piece was written. © by the author.

Risk factors for SARS-CoV-2 infection in primary and secondary school students and staff in England in the 2020/2021 school year: a longitudinal study.

OBJECTIVES: Investigate risk factors for SARS-CoV-2 infections in school students and staff. METHODS: In the 2020/2021 school year, we administered polymerase chain reaction, antibody tests, and questionnaires to a sample of primary and secondary school students and staff, with data linkage to COVID-19 surveillance. We fitted logistic regression models to identify the factors associated with infection. RESULTS: We included 6799 students and 5090 staff in the autumn and 11,952 students and 4569 staff in the spring/summer terms. Infections in students in autumn 2020 were related to the percentage of students eligible for free school meals. We found no statistical association between infection risk in primary and secondary schools and reported contact patterns between students and staff in either period in our study. Using public transports was associated with increased risk in autumn in students (adjusted odds ratio = 1.72; 95% confidence interval 1.31-2.25) and staff. One or more infections in the same household during either period was the strongest risk factor for infection in students and more so among staff. CONCLUSION: Deprivation, community, and household factors were more strongly associated with infection than contacts patterns at school; this suggests that the additional school-based mitigation measures in England in 2020/2021 likely helped reduce transmission risk in schools.

Reflecting on ’classroom readiness’ in initial teacher education in a time of global pandemic from the perspectives of eight university providers from across England, UK

In the context of a decade of change and reform in Initial Teacher Education (ITE) policy making, we assess the impact of the substantial changes caused by Covid-19 affecting ITE from the perspectives of eight university providers in England. Whilst previous research has documented the impact of the first period of lockdown in the UK, initiated in March 2020, we draw on the conceptual framework of classroom readiness to consider the continued and variable disruption caused by Covid-19 on ITE programmes in England during the period September 2020 – June 2021. Through a participatory workshop, which included identifying key questions, group discussion and written reflections with teacher educators working across eight institutions, we assess the changes to pre-service teacher education provision over this period, with a focus on postgraduate programmes. We identify that the nature and implementation of school visits and the role of technology and digital pedagogies are key areas of change during the pandemic period, whilst continuity in the value and strength of school and university partnerships remain. We consider the ways in which ideas of developing ‘classroom readiness’ have been informed and shaped through changes to teacher education brought about during the pandemic period. We argue that conceptualisations of classroom readiness need to be grounded in reflective professional learning in the context of collaborative professional communities so to enable pre-service teachers to become adaptable pastorally engaged subject specialists. We reflect on how learning from this period might be incorporated into future international ITE programmes and policy. [ FROM AUTHOR]

BSL2-compliant lethal mouse model of SARS-CoV-2 and variants of concern to evaluate therapeutics targeting the Spike protein.

Since first reported in 2019, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is rapidly acquiring mutations, particularly in the spike protein, that can modulate pathogenicity, transmission and antibody evasion leading to successive waves of COVID19 infections despite an unprecedented mass vaccination necessitating continuous adaptation of therapeutics. Small animal models can facilitate understanding host-pathogen interactions, target selection for therapeutic drugs, and vaccine development, but availability and cost of studies in BSL3 facilities hinder progress. To generate a BSL2-compatible in vivo system that specifically recapitulates spike protein mediated disease we used replication competent, GFP tagged, recombinant Vesicular Stomatitis Virus where the VSV glycoprotein was replaced by the SARS-CoV-2 spike protein (rVSV-SARS2-S). We show that infection requires hACE2 and challenge of neonatal but not adult, K18-hACE2 transgenic mice (hACE2tg) leads to productive infection of the lungs and brains. Although disease progression was faster in SARS-CoV-2 infected mice, infection with both viruses resulted in neuronal infection and encephalitis with increased expression of Interferon-stimulated Irf7, Bst2, Ifi294, as well as CxCL10, CCL5, CLC2, and LILRB4, and both models were uniformly lethal. Further, prophylactic treatment targeting the Spike protein (Receptor Binding Domain) with antibodies resulted in similar levels of protection from lethal infection against rVSV-SARS2-S and SARS-CoV-2 viruses. Strikingly, challenge of neonatal hACE2tg mice with SARS-CoV-2 Variants of Concern (SARS-CoV-2-α, -ß, ϒ, or Δ) or the corresponding rVSV-SARS2-S viruses (rVSV-SARS2-Spike-α, rVSV-SARS2-Spike-ß, rVSV-SARS2-Spike-ϒ or rVSV-SARS2-Spike-Δ) resulted in increased lethality, suggesting that the Spike protein plays a key role in determining the virulence of each variant. Thus, we propose that rVSV-SARS2-S virus can be used to understand the effect of changes to SARS-CoV-2 spike protein on infection and to evaluate existing or experimental therapeutics targeting spike protein of current or future VOC of SARS-CoV-2 under BSL-2 conditions.

Governing in the time of Covid-19: how board meetings went online and the implications of this for considering the role of the governing board

The response to the COVID-19 pandemic in 2020 necessitated changes in the working practices of many organisations such that online meetings suddenly became the norm. Governing board meetings were no exception. However, little is known about the impact of online meetings on the work of boards. Here we draw on empirical evidence from observations of in-person and online board meetings in eight colleges of further education across the UK to address the question: in what ways do governing board meetings differ in online and in-person contexts? From this we consider what this tells us about the role of the board in the life of the organisation. We conclude that social gathering, which emphasises the importance of place, is of central importance in the work of the board. [ FROM AUTHOR]

Secondary attack rates in primary and secondary school bubbles following a confirmed case: Active, prospective national surveillance, November to December 2020, England.

BACKGROUND: Following the full re-opening of schools in England and emergence of the SARS-CoV-2 Alpha variant, we investigated the risk of SARS-CoV-2 infection in students and staff who were contacts of a confirmed case in a school bubble (school groupings with limited interactions), along with their household members. METHODS: Primary and secondary school bubbles were recruited into sKIDsBUBBLE after being sent home to self-isolate following a confirmed case of COVID-19 in the bubble. Bubble participants and their household members were sent home-testing kits comprising nasal swabs for RT-PCR testing and whole genome sequencing, and oral fluid swabs for SARS-CoV-2 antibodies. RESULTS: During November-December 2020, 14 bubbles were recruited from 7 schools, including 269 bubble contacts (248 students, 21 staff) and 823 household contacts (524 adults, 299 children). The secondary attack rate was 10.0% (6/60) in primary and 3.9% (4/102) in secondary school students, compared to 6.3% (1/16) and 0% (0/1) among staff, respectively. The incidence rate for household contacts of primary school students was 6.6% (12/183) and 3.7% (1/27) for household contacts of primary school staff. In secondary schools, this was 3.5% (11/317) and 0% (0/1), respectively. Household contacts were more likely to test positive if their bubble contact tested positive although there were new infections among household contacts of uninfected bubble contacts. INTERPRETATION: Compared to other institutional settings, the overall risk of secondary infection in school bubbles and their household contacts was low. Our findings are important for developing evidence-based infection prevention guidelines for educational settings.