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Background: mRNA vaccines have proven useful in protecting vulnerable populations against SARS-CoV-2 infection. However, certain therapeutics, specifically those used in cancer treatment, reduce mRNA vaccine-induced humoral responses against SARS-CoV-2. The effects on T cell responses are not well characterized. Here, we evaluate SARS-CoV-2 spike-specific T cell responses over the course of one year in solid tumor patients in BC, Canada. Method(s): 18 female, solid-tumor patients from the BC Cancer Agency were enrolled in this prospective, cohort study, with 7 patients receiving cytotoxic chemotherapy and 11 patients receiving non-cytotoxic treatments. Whole blood was collected 1-month (T1) and one-year +/- 1-month (T2) post series completion (2 mRNA doses). Antigen-induced marker assays (AIM assays) were used to quantify CD4+ and CD8+ T cell responses, where whole blood was stimulated with ancestral or omicron SARS-CoV2 Spike peptide pools or unstimulated for 48 hours at 37degree C, fluorescently stained for activation markers CD25 and OX40 (CD4+ T cells) or CD69 and CD137 (CD8+ T cells), and analyzed using a 5-laser flow cytometer. Phenotyping of antigen-specific CD4+ T cells was done in parallel to assess the frequency of spike-specific Tregs, Th1, Th2, Th9, Th17, and Th17.1 cells. Result(s): All individuals had detectable levels of spike-specific CD4+ T cells at T2, while only 72.2% of individuals had detectable levels of spike-specific CD8+ T cells. Treatment type did not significantly impact the magnitude or phenotype of T cell responses, including those to Omicron. However, increased age was associated with decreased ancestral CD8+ T cell responses at T2. Further, ancestral and omicron responses were significantly different at T2, with decreased magnitude and altered phenotype of omicron-specific CD4+ T cells. Conclusion(s): Here, we report that solid tumor patients, treated with either chemotherapy or biologics, mount robust T cell immunity to SARS-CoV-2 following vaccination. Additional data is needed to determine if these responses correlate with antibody levels and clinical illness.
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Since 2000, literature on West (EU15) and East-Central European (EU8) welfare states has focused on a set of 'new social risks' including insecure employment and income, population ageing, unsustainable social security systems, and large-scale international immigration. Our State-of-the-Art (SOTA) article brings Russia into the dialogue on 'new social risks'. We show that broadly similar structural changes in industrial economies, labour markets and demographic patterns ended the post-World-War-Two (WWII) 'Golden Age' of welfare expansion in both the EU15 and communist states. Shared new social risks rose to the top of policy agendas. Governments responded mainly, though not exclusively, with liberalising, privatising and exclusionary policies. The SOTA compares their policy responses, specifically pension system reforms, demographic (pro-natalist and family) policies, and integration of immigrants. We find both convergence and divergence based on states' differing welfare legacies. The conclusion considers path-departing 'emergency Keynesian' responses to the COVID-19 crisis, and renewed attention to Beveridge welfare models.
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Aggression and violence amongst children have increased globally in the past decades. Within the Caribbean, this too has become a recognised trend. In Jamaica, various organisations, programmes, and projects are in place to address issues of violence amongst children and youth, particularly, within schools. Two of these programmes, INSIGHTS (focused on children’s temperaments) and Change from Within (focused on school culture change to address violence and indiscipline), are school-based initiatives implemented by a School of Education within one of the nation’s universities. Another, Operation Save Jamaica, is a non-profit charity organisation focused on sustainable development and transformation amongst individuals and communities. This chapter focuses on a partnership forged between INSIGHTS, Change from Within, Operation Save Jamaica, and an academic specialising in Social and Emotional Learning (SEL), based at the Manchester Institute of Education, England. The collaborators have partnered to organise and deliver a series of webinars focused on SEL, to support Education for Sustainable Development and Peace Education within the country and, by extension, Sustainable Development Goals 4 and 16. The paper will share feedback from webinar participants and will offer insight into how partnerships such as these can broaden the reach and scope of various interventions in this area, as well as build capacity within the higher education and education sectors. It is hoped that the experiences shared will prove useful for other entities involved in similar areas and for the forging of partnerships amongst different sectors for the furtherance of sustainability. © 2022, The Author(s), under exclusive license to Springer Nature Switzerland AG.
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Background. Prior to SARS-CoV-2 vaccination availability, medical centers workers were at significant COVID-19 (COVID) infection risk. As part of a program offering free SARS-CoV-2 serology tests to medical center employees, we examined risk factors for prior COVID infection. Methods. From Sept. to Dec. 2020, we advertised free IgG antibody testing to all Los Angeles County-Univ. of Southern California Medical Center (LAC+USC) workforce members (clinical and non-clinical) via repeated email blasts. Antibody was determined using the Abbott SARS-Cov-2 IgG test against SARS-CoV-2 nucleocapsid protein. Program participants were asked to fill out a detailed epidemiologic questionnaire about work and non-work COVID risks on their cell phone or on paper at the time of phlebotomy. All testing was done prior to COVID vaccine availability. Results. Among approximately 10,500 workforce members, 1327 had serologies done. Among those 1273 (96%) completed the questionnaire and were included in the analysis. SARS-CoV-2 IgG antibodies were found in 60 (4.7%). In bivariate analysis, we found associations between SARS-CoV-2 seropositivity and persons who previously tested positive for COVID (OR 175.8 [95% CI 77.6 - 398.6]), persons who thought they had prior COVID but tested negative (OR 3.9 [95% CI 1.3 - 11.4]), and persons who thought they had prior COVID but did not get a COVID test (OR 4.2 [95% CI 1.4 - 12.5]). In a multivariate model of SARS-CoV-2 seropositivity examining work- and non-work-related COVID exposures (Table), seropositivity was associated with work-related COVID exposure without adequate personal protective equipment (PPE) (OR 5.1 [95% CI 2.1 - 12.2]), work-related COVID exposure with adequate PPE (OR 3.5 [95% CI 1.5 - 8.0]), never wearing a mask outside of work (OR 7.1 [95% CI 1.3 - 38.4]), and Native Hawaiian/Pacific Islander race (OR 6.6 [95% CI 1.7 - 23.4]). Seropositivity was inversely associated with living at home with multiple age groups (OR 0.4 [95% CI 0.2 - 0.8]). Multivariate Model of Exposures Associated with Positive COVID Serology Among LAC+USC Workforce Members Conclusion. Among workers in a large urban medical center prior to COVID vaccine availability, SARS-CoV-2 seropositivity was associated with work-related COVID exposures and low mask use outside of work, suggesting that COVID transmission in workforce members occurs both via occupational and non-occupational routes.
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Background: The COVID-19 pandemic has drastically affected the delivery model of clinical genomic services (genetic counseling andgenetic testing) across the US and Canada. This study summarizes thesignificant changes in the clinical genomic telehealth environmentdue to the COVID-19 pandemic.Methods: Genetic counselors (GCs) in the US and Canadawho practiceclinical genetic counseling and whose service delivery model (SDM)has changed due to the pandemic were surveyed about their use oftelehealth before and after the onset of the pandemic. Data on GCattitudes toward and experience in the following fivemajor areaswerecollected and analyzed: (1) changes in utilization of their servicedelivery model (SDM), (2) the content of genetic counseling services,(3) reimbursement practices, (4) perceived benefits and limitations oftelehealth, and (5) SDM trends in the post-COVID-19 era. Datacollection occurred over four weeks in August 2020.Results: Responses of 411 eligible clinical GCs from the US and Canadawhose SDMhad changed due to the COVID-19 pandemic are included inthe analysis.We found the utilizationof in-person encounters decreasedby 69.3%;telephone encounters increased by 26.2%, and audiovisualencounters increased by 43.4%. Among the 73.8% of responders whoprovided telephone encounters, therewas an average telephone volumeincrease of 55.2%. Among the 81% of responders who providedaudiovisual encounters, there was an average audiovisual volumeincrease of 79.4%. There was a 55.5% decrease in genetic counselingservices rendered on medical campuses and in ambulatory settings.Consequently, there was a corresponding 69.4% increase in servicesrenderedathome offices.This figure parallels a72.1%increase inpatientsreceiving counseling at home and a 60.5% decrease in patients receivingcounseling at outpatient clinics and medical campuses.Before the pandemic, just 45.7% of GCs billed for telehealth services.After the beginning of the COVID-19 pandemic, 80.3% reported thatthey or their institution billed for these services.The top perceived benefits of telehealth among this sample of GCsincluded: (1) saved commute time, (2) lower patient no-show rate, (3)health safety for high-risk patients, and (4) convenience from thepatient perspective. The top perceived challenges of telehealth included: (1) coordination of services with other healthcare professionalsfor the encounter, (2) coordination of translation services fornon-English speaking patients from the clinical practice perspective,(3) poor internet connection, (4) inequality of access to technology,and (5) limited data plans available to support telehealth from thepatient perspective.Overall, 89.6% of GCs are satisfied with telehealth and identified thatthe most helpful aspect of implementing telehealth was effectivecommunication with other staff. However, 55.3% reported eitheruncertainty or an absence of a plan as to whether the newly adoptedSDM will continue post-COVID-19 and, 74.1% of respondents said theywere uncertain if there is a permanent plan to continue workingwithin the new SDM in the same setting after the pandemic.Conclusions: Telehealth usage by clinical GCs dramatically increasedduring the COVID-19 pandemic. The study results support an overallpositive experience of adopting telehealth from the perspective ofclinical GCs. Further work is needed to address barriers for patients,providers, and healthcare systems to help maintain these modalitiesas viable delivery models.(Figure Presented)(Figure Presented)
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This evidence-based practice paper will address the impact of the COVID-19 pandemic on faculty careers, offering a range of strategies higher education institutions, including engineering schools and departments, may adopt to support faculty and promote equity. Emergent research has documented immediate impacts of the pandemic across all elements of faculty work, including research (e.g. loss of access to labs and field sites), teaching (e.g. shifts to remote or hybrid instruction), and service (e.g. increased student mentoring). At the same time, faculty are differentially impacted by these challenges, with the pandemic expected to amplify longstanding inequities in career progression for women and faculty of color. In this paper, we connect the broader literature on bias and inequity in faculty career progression to more recent work specific to the pandemic, describing how these literatures informed our initial steps to respond to COVID-19 at University of Delaware. After describing our response to-date, we outline emergent challenges and strategies to improve policy implementation. We conclude by suggesting ways in which universities can continue to support faculty career development over the coming years, ensuring that pandemic impacts do not undermine progress towards gender and racial equity in faculty careers. Our preference is for this paper be presented in a traditional lecture format. © American Society for Engineering Education, 2021
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Introduction: Severe COVID-19 pneumonia is characterised by respiratory and multi-organ failure in the context of marked systemic inflammation. This hyperinflammatory syndrome is reflected by the elevation of several inflammatory molecules, such as C-reactive protein (CRP), ferritin, IL-6, troponin, and D-dimer. In a subset of patients, early intervention with signal inhibitors may treat the Covid-19 hyperinflammatory syndrome before the development of acute lung injury and organ failure. We present a summary of a study protocol for a randomised controlled, multi-arm trial with two novel inflammatory signal inhibitors;Ruxolitinib (RUX) and Fostamatinib (FOS) for the treatment of Covid-19 pneumonia. RUX is an oral Janus Associated Kinase (JAK1/JAK2) inhibitor approved for the treatment of splenomegaly, myelofibrosis and polycythaemia vera. Inhibition of STAT3 downregulates IL-6 and IL-23, which are important for the inflammatory effects of Th17 cells. Further, JAK2 inhibition has been shown to reduce levels of TNFa and CRP, as well as reducing viral cellular entry and assembly. FOS is an oral spleen tyrosine kinase (SYK) inhibitor approved for the treatment of chronic immune thrombocytopenia. Studies of severe acute respiratory distress syndrome (ARDS) suggest that the pathogenesis relies on a series of SYK events leading to cytokine and chemokine release. FOS acts by inhibiting SYK activity, blocking the production and release of cytokines induced via C-lectin receptors and Fc receptor activation, ameliorating the cytokine storm which precedes ARDS. Primary Objective: The primary objective of MATIS is to determine the efficacy of RUX or FOS compared to standard of care (SOC) to reduce the proportion of hospitalised patients progressing from mild or moderate to severe COVID-19 pneumonia at 14 days from baseline. Secondary objectives at 7, 14 and 28 days: - Determine the efficacy of RUX or FOS to reduce mortality - Determine the efficacy of RUX or FOS to reduce the need for invasive ventilation or ECMO - Determine the efficacy of RUX or FOS to reduce the need for non-invasive ventilation - Determine the efficacy of RUX or FOS to reduce the proportion of patients suffering significant oxygen desaturation - Determine the efficacy of RUX or FOS to reduce the need for renal replacement therapy - Determine the efficacy of RUX and FOS to reduce the incidence of venous thromboembolism COVID-19 pneumonia - Determine the efficacy of RUX and FOS to reduce the severity of COVID-19 pneumonia [graded by a modified WHO Ordinal Scale] - Determine the efficacy of RUX or FOS to reduce the level of inflammatory biomarkers - Determine the efficacy of RUX or FOS to reduce the duration of hospital admission - Evaluate the safety of RUX and FOS for COVID-19 pneumonia Study Design: This is a multi-arm, two-stage, open-label, randomised (1:1:1) controlled trial. Participants will be recruited during hospitalisation for COVID-19 in multiple centres in the UK. Eligible participants (table 1) are randomised to one of the three interventions (RUX, FOS, SOC) by a central web-based randomisation service. This uses randomisation sequences with random block sizes, stratified by age (<65 and ≥65 years) and site. The treatment duration is 14 days from baseline. Patients receiving RUX will be administered 10mg BD for Day 1-7 and 5mg BD for Day 8-14. FOS will be administered as 150mg BD day 1-7 and 100mg BD day 8-14. Participants receive follow up assessments on days 7, 14 and 28 after the first dose. Outcomes: Primary endpoints will be assessed with a pairwise comparison (FOS vs SOC and RUX vs SOC) of the proportion of participants diagnosed with severe COVID-19 pneumonia within 14 days. Severe COVID-19 pneumonia is defined by a modified WHO COVID-19 Ordinal Score 5, comprising the following indicators of disease severity: - Death - Requirement for invasive ventilation - Requirement for non-invasive ventilation including CPAP or high flow oxygen - O2 saturation < 90% on 60% inspired oxygen Samples size: In stage 1 of this multi-arm study, 171 parti ipants will be randomised (57 per arm). Following an interim analysis, if either intervention shows a signal of efficacy, stage 2 will recruit a further 95 participants per arm (Fig 1). Trial Status: Recruitment is ongoing and commenced 2nd October 2020. Currently 127 patients are recruited and stage 1 is projected to be completed by 1st September 2021. The full protocol can be accessed via the trial's website. [Formula presented] Disclosures: Milojkovic: Novartis: Honoraria, Speakers Bureau;Incyte: Honoraria, Speakers Bureau;Bristol-Myers Squibb: Honoraria, Speakers Bureau;Pfizer: Honoraria, Speakers Bureau. Cooper: Principia and Sanofi: Consultancy;Sanofi and Principia: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: travel, accommodations expenses. OffLabel Disclosure: Fostamatanib - is a tyrosine kinase inhibitor with activity against spleen tyrosine kinase (SYK). In the context of treating COVID-19, Fostamatanib acts by inhibiting SYK activist, blocking the production and release of cytokines induced via C-lectin receptors and Fc receptor activation, ameliorating the cytokine storm which precedes ARDS. Studies of severe acute respiratory syndrome induced by coronavirus, suggest that pathogenesis relies on a series of SYK events. SYK medicates ctuokine and chemokine release, induced by the activation of C-lectin receptors and immunoglobulin Fc receptors, resulting in neutrophil and monocyte lung ingress, sequential activation of neutrophil extracellular traps and activation of lung epithelium and multiple myeloid cell. This is followed by inflammation and tissue destruction that contribute to ARDS. Ruxolitinib - A JAK1/JAK2 inhibitor. JAK and STAT molecules are proteins that trance extracellular stimulation into intracellular signalling, leading to expression of host inflammatory cytokines and a variety of immune cells. In the context of MATIS, we use low dose ruxolitinib to treat COVID-19 by targeting key signalling pathways implicated in the hyper-inflammatory response of patients with COVID-19 infection. The mechanisms of Ruxolitinib to act in COVID-19 is through inhibition of STAT3 activation, down regulating IL-6 and IL-23, signalling important for the inflammatory effects of Th17 cells. Furthermore it leads to reductions of TNFa and CRP.
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Orientation: The coronavirus disease 2019 (COVID-19) pandemic led to fundamental changes in the workplace for many, particularly healthcare workers. Research purpose: This study explored healthcare workers’ (ophthalmologists, nurses and support staff) experiences of anxiety, depression, burnout, resilience and coping strategies during lockdown Levels 2 and 3 in an Ophthalmic consulting practice and hospital in South Africa. Motivation for the study: The increased workplace stress and vulnerability associated with working during the COVID-19 pandemic introduced an unprecedented level of risk for healthcare workers. Factors contributing to psychological distress must be identified and appropriately mitigated, to prevent dire human and economic costs. Research approach/design and method: A survey was sent out at two separate times to a convenience sample of 31 and 15 healthcare workers respectively. The survey consisted of a demographics section, Hospital Anxiety and Depression Scale, Burnout Measure short-version, Brief Cope Inventory, Connor Davidson Resilience Inventory and six open-ended questions investigating personal health and support experiences during COVID-19. Descriptive analyses and thematic analysis were used for data analysis. Main findings: The sample of healthcare workers experienced some degree of psychological distress, including anxiety, burnout and a lack of social support on both surveys. However, these symptoms were alleviated by personal factors, including positive coping mechanisms, high resilience and organisational support. Practical/managerial implications: Healthcare facilities should consider in-house structures focusing on building resilience and positive coping mechanisms, whilst ensuring that workplace conditions are optimal for staff members. Contribution/value-add: This study provides some insight into both the risk and protective factors experienced by health workers during the COVID-19 pandemic. © 2021. The Authors. Licensee: AOSIS. This work.
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Purpose: Social work teams can provide a secure base for social workers, supporting them to manage the emotional demands of child and family social work (Biggart et al., 2017). As the COVID-19 pandemic has necessitated increased remote working, social workers have needed to maximise their use of virtual networks and navigate new ways of connecting with colleagues. This study aims to examine the extent to which social work teams can function as a secure base in the context of remote working. Design/methodology/approach: Between 19th March and 13th June, the authors undertook 31 in-depth, qualitative interviews with child and family social workers across 9 local authorities in England. this research captured social workers’ perspectives on remote working and team support throughout lockdown in England. Findings: In this study, the authors report findings in three key areas: how social workers experienced the sudden shift to increased remote working;how social work teams provided a secure base for remote working;and the challenges for sustaining the team as a secure base when working remotely. Originality/value: These findings will be of interest to social workers, managers and local authorities as they adapt to the challenges of increased remote working in child and family social work. © 2020, Emerald Publishing Limited.