Bivalent intra-spike binding provides durability against emergent Omicron lineages: Results from a global consortium.

The SARS-CoV-2 Omicron variant of concern (VoC) and its sublineages contain 31-36 mutations in spike and escape neutralization by most therapeutic antibodies. In a pseudovirus neutralization assay, 66 of the nearly 400 candidate therapeutics in the Coronavirus Immunotherapeutic Consortium (CoVIC) panel neutralize Omicron and multiple Omicron sublineages. Among natural immunoglobulin Gs (IgGs), especially those in the receptor-binding domain (RBD)-2 epitope community, nearly all Omicron neutralizers recognize spike bivalently, with both antigen-binding fragments (Fabs) simultaneously engaging adjacent RBDs on the same spike. Most IgGs that do not neutralize Omicron bind either entirely monovalently or have some (22%-50%) monovalent occupancy. Cleavage of bivalent-binding IgGs to Fabs abolishes neutralization and binding affinity, with disproportionate loss of activity against Omicron pseudovirus and spike. These results suggest that VoC-resistant antibodies overcome mutagenic substitution via avidity. Hence, vaccine strategies targeting future SARS-CoV-2 variants should consider epitope display with spacing and organization identical to trimeric spike.

Teaching and learning lifestyle medicine during COVID-19: how has living during a pandemic influenced students' understanding and attitudes to self-care and population health? A qualitative analysis.

BACKGROUND: In 2019 a new Lifestyle Medicine (LM) module was introduced to the undergraduate medical curriculum at Imperial College London. Lifestyle Medicine is an emergent discipline which aims to tackle the increasing burden of non-communicable disease. Previous work has suggested that students value clinical teaching over traditional Public Health topics. Taking a constructivist view of learning, this paper assesses changes in medical students' attitudes towards Public Health and LM in response to living through a pandemic. We then make suggestions as to how this lived experience might be useful in teaching LM, and discuss the interaction between teaching, behaviour, and experience with consideration of self-determination theories in learning. METHODS: First-year medical students were surveyed at the end of their first year of teaching and asked if living during the COVID-19 pandemic had changed the value they place on LM and if so, how. Thematic analysis was conducted on responses representing 71% (n = 216) of the year group. RESULTS: Four themes were defined in the data: acknowledging importance; impact on behaviour; health inequalities and the wider determinants; and promoting Public Health and prevention. These themes highlight the distinct levels through which the pandemic has had an impact: from personal behaviour to population health. CONCLUSIONS: This is the first study to look at the impact of living through a pandemic on attitudes to LM. Our results suggest that the pandemic has led to increased reflection on health behaviours. The lived-experience of COVID-19 may facilitate a better understanding of health inequalities and their impact, alongside the opportunities presented by effective LM interventions.