Psychometric development of the COVID-19 vaccine misinformation scale and effects on vaccine hesitancy

To help inform post-COVID-19 pandemic practical health policies, the researchers created the COVID-19 vaccine misinformation scale (CVMS). During the COVID-19 pandemic, falsehoods spread online which casted doubt and concerns about the vaccine. Example misconceptions included vaccination leads to greater vulnerability to other illness and would alter someone’s DNA. The researchers performed two large surveys with U.S. participants. The researchers reviewed debunked COVID-19 vaccine falsehoods online. Construction of the CVMS followed standard psychometric scale development steps. Statistical analysis provided support for the 10-item CVMS with satisfactory reliability, discriminant validity, and convergent validity. Predictive validity regression analysis demonstrated the CVMS associated with higher vaccine hesitancy. The prevalence of vaccine misbeliefs broadened pandemic healthcare challenges. On top of existing duties, healthcare workers had to explain vaccine efficacy and safety to dispel fallacies. The researchers discuss implications for the CVMS within the context of motivated reasoning theory.

Telehealth for Opioid Use Disorder: One Year Retention during the US COVID-19 Pandemic (preprint)

Objective: To determine retention in care for opioid use disorder when treated solely via telehealth with a harm reduction, low-threshold model. Methods: Retrospective cohort analysis of aggregated, anonymized data from 991 patients in telehealth-based buprenorphine treatment. The cohort consisted of patients with commercial or governmental insurance who enrolled between May 17, 2019 andSeptember 28, 2021. Analysis was extended to a maximum of one year for each patient. Results: At one year, retention in care was 55% overall. When analyzed separately, retention at one year was 62% for patients with commercial insurance and 53% for those with governmental insurance. Conclusions: Telehealth-based treatment of opioid use disorder can achieve retention in care for patients—with governmental or commercial insurance—that is superior to inperson treatment as usual. Policy implications: Telehealth for opioid use disorder can be effective for patients over a range of incomes. Regulatory action allowing telehealth-only care

Evolution of the SARS-CoV-2 spike protein in the human host (preprint)

Variants of SARS-CoV-2 have emerged which contain multiple substitutions in the surface spike glycoprotein that have been associated with increased transmission and resistance to neutralising antibodies and antisera. We have examined the structure and receptor binding properties of spike proteins from the B.1.1.7 (UK) and B.1.351 (SA) variants to better understand the evolution of the virus in humans. Both variants’ spikes have the same mutation, N501Y, in their receptor-binding domains that confers tighter ACE2 binding and this substitution relies on a common earlier substitution (D614G) to achieve the tighter binding. Each variant spike has also acquired a key change in structure that impacts virus pathogenesis. Unlike other SARS-CoV-2 spikes, the spike from the UK variant is stable against detrimerisation on binding ACE2. This feature primarily arises from the acquisition of a substitution at the S1-S2 furin site that allows for near-complete cleavage. In the SA variant spike, the presence of a new substitution, K417N, again on the background of the D614G substitution, enables the spike trimer to adopt fully open conformations that are required for receptor binding. Both types of structural change likely contribute to the increased effectiveness of these viruses for infecting human cells.

Sequential receptor binding primes the SARS-CoV-2 S glycoprotein for membrane fusion (preprint)

SARS-CoV-2 infection is initiated by virus binding to ACE2 cell surface receptors, followed by fusion of virus and cell membranes to release the virus genome into the cell. Both receptor binding and membrane fusion activities are mediated by the virus spike glycoprotein, S. As with other class I membrane fusion proteins, S is post-translationally cleaved, in this case by furin, into S1 and S2 components that remain associated following cleavage. Fusion activation following receptor binding is proposed to involve the exposure of a second proteolytic site (S2’), cleavage of which is required for the fusion peptide release. We have investigated the binding of ACE2 to the furin-cleaved form of SARS-CoV-2 S by cryoEM. We classify ten different molecular species including the unbound, closed spike trimer, the fully open ACE2-bound trimer, and dissociated monomeric S1 bound to ACE2. The ten structures describe sequential ACE2 binding events which destabilise the spike trimer, progressively opening up, and out, the individual S1 components. The opening process reduces S1 contacts with each other and un-shields the trimeric S2 core, priming fusion activation and dissociation of ACE2-bound S1 monomers. The structures also reveal refolding of one of the S1 subdomains, following ACE2 binding, that disrupts interactions with S2, notably involving Asp614, leading to destabilisation of the structure of S2 proximal to the secondary (S2’) cleavage site.

Antibody-mediated disruption of the SARS-CoV-2 spike glycoprotein (preprint)

The CR3022 antibody, selected from a group of SARS-CoV-1 monoclonal antibodies for its ability to cross-react with SARS-CoV-2, has been examined for its ability to bind to the ectodomain of the SARS-CoV-2 spike glycoprotein. Using electron cryo-microscopy we show that antibody binding requires rearrangements in the S1 domain that result in dissociation of the spike.

Evolution of SARS-CoV-2 spike glycoprotein (preprint)

The spike glycoprotein (S) of SARS-CoV-2 mediates attachment of the virus to cell surface receptors and fusion between virus and cell membranes1. The receptor for SARS-CoV-2, like that for SARS-CoV, is the human cell-surface membrane protein ACE22–4. Membrane fusion activity, as for other class-1 fusion glycoproteins, requires S to be proteolytically cleaved into S1 and S2 that remain associated following cleavage4–7. SARS-CoV-2 is thought to have emerged from bats, possibly via a secondary host8,9. To better understand the transmission of SARS-CoV-2 we have determined the structure of its furin-cleaved S by cryoEM, which shows that cleavage at this polybasic amino-acid site increases the structural plasticity of the receptor binding region and facilitates the adoption of an open conformation that is required for it to bind to the ACE2 receptor. To investigate relationships between S proteins of SARS-CoV-2 and of the most closely related bat virus, RaTG138, we have determined and compared their structures and characterised biochemically their affinities for ACE2 and their relative stabilities. Whilst the overall structures are similar, there are key differences likely pertinent to virus infectivity. These include a more stable pre-cleavage form of human S, about 1000-fold tighter binding of SARS-CoV-2 to human receptor, and a higher proportion of S in the conformation required for binding ACE2 upon protease cleavage.