Background and objectives
Because of its beneficial off‐target effects against non‐mycobacterial infectious diseases, bacillus Calmette–Guérin (BCG) vaccination might be an accessible early intervention to boost protection against novel pathogens. Multiple epidemiological studies and randomised controlled trials (RCTs) are investigating the protective effect of BCG against coronavirus disease 2019 (COVID‐19). Using samples from participants in a placebo‐controlled RCT aiming to determine whether BCG vaccination reduces the incidence and severity of COVID‐19, we investigated the immunomodulatory effects of BCG on in vitro immune responses to SARS‐CoV‐2.
Methods
This study used peripheral blood taken from participants in the multicentre RCT and BCG vaccination to reduce the impact of COVID‐19 on healthcare workers (BRACE trial). The whole blood taken from BRACE trial participants was stimulated with γ‐irradiated SARS‐CoV‐2‐infected or mock‐infected Vero cell supernatant. Cytokine responses were measured by multiplex cytokine analysis, and single‐cell immunophenotyping was made by flow cytometry.
Results
BCG vaccination, but not placebo vaccination, reduced SARS‐CoV‐2‐induced secretion of cytokines known to be associated with severe COVID‐19, including IL‐6, TNF‐α and IL‐10. In addition, BCG vaccination promoted an effector memory phenotype in both CD4+ and CD8+ T cells, and an activation of eosinophils in response to SARS‐CoV‐2.
Conclusions
The immunomodulatory signature of BCG’s off‐target effects on SARS‐CoV‐2 is consistent with a protective immune response against severe COVID‐19.
The Community Challenge is a simulated community event for pre-registration nursing students across all four fields. Through the provision of real-time simulation, the Community Challenge has combined a deeper learning for both nursing students and the drama students who were involved in making the scenarios real and interactive. The event was run over 5 days, with positive evaluations from students and staff. Furthermore, Community Challenge has been found to be successful in expanding opportunities for students that align with national drivers, curriculum planning and interprofessional learning. The event has allowed students to engage in learning with other fields, enhancing their own practice. The Community Challenge has been found to enhance the link between theory and practice within primary care, promoting the relevance and importance of community care within nursing.
The ECJ’s use of a breach/justification methodology to adjudicate tensions between free movement and fundamental rights has led to criticism that it prioritizes the former over the latter. While this article agrees that the structural presentation of fundamental rights as a “defence” to a prima facie restriction of free movement under the current adjudicative framework is problematic, it rejects the argument that this is evidence of some contestable subjective attitude on the part of the ECJ. Rather, it develops the position that the breach/justification model is the product of free movement’s historical and ongoing significance within EU law. Crucially, it explains the specific constitutional drivers – such as the expansion in free movement’s material and personal scope, the extension of its direct effect, and the strengthening of a decentralized enforcement system – that brought free movement into more frequent and more abrasive contact with fundamental rights. It is these developments that rendered the previously unproblematic breach/justification methodology a cause for concern.
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