Immunoglobulin replacement products protect against SARS-CoV-2 infection in vivo despite poor neutralizing activity.

Immunoglobulin (IG) replacement products are used routinely in patients with immune deficiency and other immune dysregulation disorders who have poor responses to vaccination and require passive immunity conferred by commercial antibody products. The binding, neutralizing, and protective activity of intravenously administered IG against SARS-CoV-2 emerging variants remains unknown. Here, we tested 198 different IG products manufactured from December 2019 to August 2022. We show that prepandemic IG had no appreciable cross-reactivity or neutralizing activity against SARS-CoV-2. Anti-spike antibody titers and neutralizing activity against SARS-CoV-2 WA1/2020 D614G increased gradually after the pandemic started and reached levels comparable to vaccinated healthy donors 18 months after the diagnosis of the first COVID-19 case in the United States in January 2020. The average time between production to infusion of IG products was 8 months, which resulted in poor neutralization of the variant strain circulating at the time of infusion. Despite limited neutralizing activity, IG prophylaxis with clinically relevant dosing protected susceptible K18-hACE2-transgenic mice against clinical disease, lung infection, and lung inflammation caused by the XBB.1.5 Omicron variant. Moreover, following IG prophylaxis, levels of XBB.1.5 infection in the lung were higher in FcγR-KO mice than in WT mice. Thus, IG replacement products with poor neutralizing activity against evolving SARS-CoV-2 variants likely confer protection to patients with immune deficiency disorders through Fc effector function mechanisms.

Practitioner Review: Effectiveness and mechanisms of change in participatory arts-based programmes for promoting youth mental health and well-being - a systematic review.

BACKGROUND: Participatory arts-based (PAB) programmes refer to a diverse range of community programmes involving active engagement in the creation process that appear helpful to several aspects of children's and young people's (CYP) mental health and well-being. This mixed-methods systematic review synthesises evidence relating to the effectiveness and mechanisms of change in PAB programmes for youth. METHOD: Studies were identified following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses approach. Eleven electronic databases were searched for studies of PAB programmes conducted with CYP (aged 4-25 years), which reported mental health and well-being effectiveness outcomes and/or mechanisms of change. A mixed-methods appraisal tool assessed study quality. A narrative synthesis was conducted of effectiveness and challenges in capturing this. Findings relating to reported mechanisms of change were integrated via a metasummary. RESULTS: Twenty-two studies were included. Evidence of effectiveness from quantitative studies was limited by methodological issues. The metasummary identified mechanisms of change resonant with those proposed in talking therapies. Additionally, PAB programmes appear beneficial to CYP by fostering a therapeutic space characterised by subverting restrictive social rules, communitas that is not perceived as coercive, and inviting play and embodied understanding. CONCLUSIONS: There is good evidence that there are therapeutic processes in PAB programmes. There is a need for more transdisciplinary work to increase understanding of context-mechanism-outcome pathways, including the role played by different art stimuli and practices. Going forward, transdisciplinary teams are needed to quantify short- and long-term mental health and well-being outcomes and to investigate optimal programme durations in relation to population and need. Such teams would also be best placed to work on resolving inter-disciplinary methodological tensions.

Modelling arts professionals' wellbeing and career intentions within the context of COVID-19.

The COVID-19 pandemic had a substantial effect on the creative and cultural industries in the United Kingdom (UK), as seen in our first snapshot of the HEartS Professional Survey (April-June 2020, Phase 1, N = 358). By analysing data collected one year later (April-May 2021, Phase 2, N = 685), the aims of the current study are to trace the contributors to (1) arts professionals' mental and social wellbeing and (2) their expectations of staying in the arts. Findings show that artists continued to experience challenges in terms of finances, and mental and social wellbeing. Over half of the respondents reported financial hardship (59%), and over two thirds reported being lonelier (64%) and having increased anxiety (71%) than before the pandemic. Hierarchical multiple linear regression models, using the Mental Health Continuum-Short Form, Center for Epidemiologic Studies Depression Scale, Social Connectedness Scale, and Three-Item Loneliness Scale as outcome variables, indicate that perceived financial hardship continued to be associated with higher depression and loneliness scores. As in our first study, more physical activity before lockdown was associated with higher wellbeing and social connectedness scores, and higher self-rated health scores were associated with higher wellbeing and lower depression scores. Similarly, increases in physical activity during lockdown, as well as older age, were still associated with higher wellbeing and social connectedness scores and with lower depression and loneliness scores. An ordinal logistic regression model indicated three contributors to artists' professional expectations of remaining in the arts: greater proportion of income from the arts pre-pandemic, continued maintenance of skills, and greater proportion of freelance work. The results suggest that the wellbeing patterns observed at the start of the pandemic remained consistent a year on. They point to possible strategies to support wellbeing and underline the importance of finances for expectations of remaining in arts professions.

mRNA vaccine boosting enhances antibody responses against SARS-CoV-2 Omicron variant in individuals with antibody deficiency syndromes.

Individuals with primary antibody deficiency (PAD) syndromes have poor humoral immune responses requiring immunoglobulin replacement therapy. We followed individuals with PAD after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination by evaluating their immunoglobulin replacement products and serum for anti-spike binding, Fcγ receptor (FcγR) binding, and neutralizing activities. The immunoglobulin replacement products tested have low anti-spike and receptor-binding domain (RBD) titers and neutralizing activity. In coronavirus disease 2019 (COVID-19)-naive individuals with PAD, anti-spike and RBD titers increase after mRNA vaccination but wane by 90 days. Those vaccinated after SARS-CoV-2 infection develop higher and more sustained responses comparable with healthy donors. Most vaccinated individuals with PAD have serum-neutralizing antibody titers above an estimated correlate of protection against ancestral SARS-CoV-2 and Delta virus but not against Omicron virus, although this is improved by boosting. Thus, some immunoglobulin replacement products likely have limited protective activity, and immunization and boosting of individuals with PAD with mRNA vaccines should confer at least short-term immunity against SARS-CoV-2 variants, including Omicron.

The future of the cultural workforce: Perspectives from early career arts professionals on the challenges and future of the cultural industries in the context of COVID-19.

The COVID-19 pandemic has had a profound impact on the arts sector, disrupting livelihoods and professional networks and accentuating the instability that is common for creative workers. Gaps in support for grassroots organisations and freelance workers have highlighted structural inequalities within the industry, and the significant challenges for individual workers in the early stages of their career. Yet, the pandemic has also emphasised the importance of the arts as a community resource and its role in supporting wellbeing and togetherness. This qualitative study explored the experiences of the pandemic for early career arts workers, focusing on its impacts upon their livelihoods and how it has shaped their future career directions. Sixteen arts and cultural workers across a variety of sectors including theatre, film, circus, music, and literature participated in solo, semi-structured interviews during April-June 2021. Thematic analysis identified three overarching themes: (i) 'Pandemic precarity and creative practice', (ii) 'PostCOVID I: Inclusivity and diversifying audiences', and (iii) 'PostCOVID II: Adapting, developing, and disrupting cultural practices'. Overall, the experiences capture an early career workforce that, while committed and engaged with their creative practice, also seeks a more equitable, fairer, and diverse industry that protects artists and engages more flexibly with broader audiences.

SARS-CoV-2 booster vaccination rescues attenuated IgG1 memory B cell response in primary antibody deficiency patients.

Background: Although SARS-CoV-2 vaccines have proven effective in eliciting a protective immune response in healthy individuals, their ability to induce a durable immune response in immunocompromised individuals remains poorly understood. Primary antibody deficiency (PAD) syndromes are among the most common primary immunodeficiency disorders in adults and are characterized by hypogammaglobulinemia and impaired ability to mount robust antibody responses following infection or vaccination. Methods: Here, we present an analysis of both the B and T cell response in a prospective cohort of 30 individuals with PAD up to 150 days following initial COVID-19 vaccination and 150 days post mRNA booster vaccination. Results: After the primary vaccination series, many of the individuals with PAD syndromes mounted SARS-CoV-2 specific memory B and CD4+ T cell responses that overall were comparable to healthy individuals. Nonetheless, individuals with PAD syndromes had reduced IgG1+ and CD11c+ memory B cell responses following the primary vaccination series, with the defect in IgG1 class-switching rescued following mRNA booster doses. Boosting also elicited an increase in the SARS-CoV-2-specific B and T cell response and the development of Omicron-specific memory B cells in COVID-19-naïve PAD patients. Individuals that lacked detectable B cell responses following primary vaccination did not benefit from booster vaccination. Conclusion: Together, these data indicate that SARS-CoV-2 vaccines elicit memory B and T cells in most PAD patients and highlights the importance of booster vaccination in immunodeficient individuals.