Investigating neutrophil function during SARS-CoV2 infection in human airway epithelial cells from elderly and young individuals

The COVID-19 pandemic caused by the SARS-CoV2 virus poses a global health threat with over 5 million deaths recorded. There is little understanding regarding SARS-CoV2 pathogenesis in the human airways and disease severity increases with age. Neutrophils are white blood cells found in large numbers in the airways of the lungs in severe COVID-19 patients. It is not known whether this influx of neutrophils into the airway has a protective or detrimental effect. We aim to understand the role of neutrophils during COVID-19 pathology, using an experimental infection model of the airway epithelium from the eldelry and children. To do this, we collect nasal airway cells from healthy elderly and children and grow them at air-liquid interface. Once differentiation and ciliation of these cells is reached, we infect the cells with SARS-CoV2 virus and allow neutrophils to migrate from the basolateral (blood) to the apical (air) side of the epithelium, similar to a physiological airway. Using flow cytometric analyses, we measure the expression of activation markers and the number of neutrophils that migrate across the epithelium of different ages in response to SARS-CoV2 infection. Preliminary work shows less viable neutrophils recovered from the elderly epithelium, more activated neutrophils when migrating through the elderly epithelium, as well as increased numbers of neutrophils remaining on the basolateral (blood) side of the elderly epithelium. These findings point to an inflammatory neutrophil phenotype influenced by the damaged elderly epithelium and supports the hypothesis that neutrophils are responsible for the severity of disease.

siRNA silencing of cellular entry proteins as a gene therapy strategy for Covid-19

SARS-CoV-2 remains a significant public health threat, causing severe respiratory illness in susceptible individuals. Several effective Covid-19 vaccines have been developed but novel SARS-CoV-2 variants continuously emerge that are more transmissible and have potential to evade vaccine immune responses. We are developing a novel therapy that does not depend on an immune response, based on siRNA-mediated silencing of Angiotensin-converting enzyme 2 (ACE2) receptor and Transmembrane Serine Protease 2 (TMPRSS2). SARS-CoV-2 requires these host proteins to enter respiratory epithelial cells at the cell surface, through binding and priming of its Spike protein. As a cell model for SARS-CoV-2 infection, we have utilised primary nasal epithelial cells (NHNE), as well as HEK293T cells overexpressing ACE2 and TMPRSS2. siRNA transfection in NHNE cells led to a 78%-88% knockdown of ACE2 and TMPRSS2, as determined by qRT-PCR and western blot data. TMPRSS2 knockdown in the overexpressing HEK293T cells resulted in an 87% reduction in infectivity from SARS-CoV-2 Spike-pseudotyped lentiviruses expressing a luciferase transgene, indicative of a significant reduction in virus entry (p < 0.0001 by one-way ANOVA). We are now working to confirm these results with live SARS-CoV-2 and to test lipid nanoparticle delivery of the siRNAs to air-liquid interface grown NHNEs to more accurately model the respiratory airway. This siRNA approach could provide a novel therapy for immunocompromised individuals who do not gain sufficient protection from SARS-CoV-2 vaccines. Additionally, by targeting host proteins rather than virus components, our therapy is likely to remain effective in spite of emerging SARS-CoV-2 variants that circumvent pre-existing immune responses.

Selected Strategies and Techniques for Counseling Survivors of Trauma in the Time of COVID-19

This chapter describes a range of techniques and strategies to facilitate trauma recovery. Included are examples from emotional, somatic, neurobiological, relational, and cognitive approaches to trauma-informed treatment. The chapter discusses techniques that are based on Herman’s (1992/2015) three-phase model of safety/stabilization, working through, and reconnection, as well as integrative techniques based on a holistic approach to trauma recovery. These tools both empower survivors to self-regulate and to avoid retraumatization, with or without processing the trauma story through talk- or narrative therapy. Finally, individualized tools for addressing client and counselor self-care and self-regulation, shared trauma, and traumatic grief are discussed, with a special focus on trauma treatment during the global pandemic of COVID-19. © 2023 Springer Publishing Company, LLC and 2012. All rights reserved.29

Socially responsible operations in the Industry 4.0 era: post-COVID-19 technology adoption and perspectives on future research

Purpose As focal firms in supply networks reflect on their experiences of the pandemic and begin to rethink their operations and supply chains, there is a significant opportunity to leverage digital technological advances to enhance socially responsible operations performance (SROP). This paper develops a novel framework for exploring the adoption of Industry 4.0 technologies for improving SROP. It highlights current best-practice examples and presents future research pathways. Design/methodology/approach This viewpoint paper argues how Industry 4.0 technology adoption can enable effective SROP in the post-COVID-19 era. Academic articles, relevant grey literature, and insights from industry experts are used to support the development of the framework. Findings Seven technologies are identified that bring transformational capabilities to SROP, i.e. big data analytics, digital twins, augmented reality, blockchain, 3D printing, artificial intelligence, and the Internet of Things. It is demonstrated how these technologies can help to improve three sub-themes of organisational social performance (employment practices, health and safety, and business practices) and three sub-themes of community social performance (quality of life and social welfare, social governance, and economic welfare and growth). Research limitations/implications A research agenda is outlined at the intersection of Industry 4.0 and SROP through the six sub-themes of organisational and community social performance. Further, these are connected through three overarching research agendas: "Trust through Technology", "Responsible Relationships" and "Freedom through Flexibility". Practical implications Organisational agendas for Industry 4.0 and social responsibility can be complementary. The framework provides insights into how Industry 4.0 technologies can help firms achieve long-term post-COVID-19 recovery, with an emphasis on SROP. This can offer firms competitive advantage in the "new normal" by helping them build back better. Social implications People and communities should be at the heart of decisions about rethinking operations and supply chains. This paper expresses a view on what it entails for organisations to be responsible for the supply chain-wide social wellbeing of employees and the wider community they operate in, and how they can use technology to embed social responsibility in their operations and supply chains. Originality/value Contributes to the limited understanding of how Industry 4.0 technologies can lead to socially responsible transformations. A novel framework integrating SROP and Industry 4.0 is presented.

COVID-19: Extensive epithelial damage and ciliary dyskinesia in hospitalised patients.

Infection with SARS-CoV-2 can cause severe respiratory disease and it is predicted that the COVID-19 pandemic will leave a substantial number of patients with long-term respiratory complications (1).

The local and systemic response to SARS-CoV-2 infection in children and adults

T1 Figure 1ConclusionsOverall, this largest paediatric single cell COVID-19 study to date showed significant differences in response to SARS-CoV-2 between children and adults, reflecting the changes of the immune landscape over developmental time, which in children are dominated by naïve and innate responses.