Understanding Factors Impacting Coronavirus Disease 2019 Vaccine Hesitancy in a Rural Surgical Clinic.

Objective: Evaluate patient hesitancy about the coronavirus disease 2019 (COVID-19) vaccine. Patients and Methods: English and Spanish pre-and post-video surveys were completed by patients at rural surgery clinics. The surveys consisted of 25 or 21 five-point Likert statements, respectively. Paired difference t-tests and independent sample t-tests were performed. Results: Ninety-four patients completed the surveys: 137 females (73%) and 51 (27%) males; 113 patients were Hispanic (64%); 63 patients were white (36%). The pre-video survey showed that the top two factors influencing patients were: preference for wearing masks over vaccination (n = 185; x¯ = 3.55) and not trusting the effectiveness of the vaccine (n = 186; x¯ = 3.01). Patients agreed that the video made them want to talk to their family about getting vaccinated (n = 176; x¯ = 3.14) and made them appreciate that they can get really sick from COVID-19 (n = 177; x¯ = 3.14). After watching the video, women of childbearing age (WCBA; n = 65; x¯ = 3.20) agreed more that the video made them want to get the COVID-19 vaccine than non-WCBA (n = 59; x¯ = 2.37; p = 0.0123). Women of childbearing age (n = 66; x¯ = 3.32) also agreed more that the video made them appreciate that they can get really sick from the COVID virus than non-WCBA (n = 60; x¯ = 2.58; p = 0.0254). Post-video statements showed that patients agreed that the video was easy to understand, they liked the video, and the video was helpful. Conclusions: There is room to better inform patients in a rural setting, especially WCBA, about COVID-19 illness and vaccination through video testimonies. Surgeons are uniquely positioned to offer effective recommendations, to increase vaccination rates, and address vaccine hesitancy.

Modelling SARS-CoV-2 spike-protein mutation effects on ACE2 binding.

The binding affinity of the SARS-CoV-2 spike (S)-protein to the human membrane protein ACE2 is critical for virus function. Computational structure-based screening of new S-protein mutations for ACE2 binding lends promise to rationalize virus function directly from protein structure and ideally aid early detection of potentially concerning variants. We used a computational protocol based on cryo-electron microscopy structures of the S-protein to estimate the change in ACE2-affinity due to S-protein mutation (ΔΔGbind) in good trend agreement with experimental ACE2 affinities. We then expanded predictions to all possible S-protein mutations in 21 different S-protein-ACE2 complexes (400,000 ΔΔGbind data points in total), using mutation group comparisons to reduce systematic errors. The results suggest that mutations that have arisen in major variants as a group maintain ACE2 affinity significantly more than random mutations in the total protein, at the interface, and at evolvable sites. Omicron mutations as a group had a modest change in binding affinity compared to mutations in other major variants. The single-mutation effects seem consistent with ACE2 binding being optimized and maintained in omicron, despite increased importance of other selection pressures (antigenic drift), however, epistasis, glycosylation and in vivo conditions will modulate these effects. Computational prediction of SARS-CoV-2 evolution remains far from achieved, but the feasibility of large-scale computation is substantially aided by using many structures and mutation groups rather than single mutation effects, which are very uncertain. Our results demonstrate substantial challenges but indicate ways forward to improve the quality of computer models for assessing SARS-CoV-2 mutation effects.