Primary care delivery of behavioral weight loss services for adults with cardiovascular risk factors: development of pragmatic implementation strategies and results of a randomized feasibility trial (preprint)

Background Intensive lifestyle interventions (ILI) improve weight loss and cardiovascular risk factors, but health systems face challenges implementing them. We engaged stakeholders to cocreate and evaluate feasibility of primary care implementation strategies and of a pragmatic randomization procedure to be used for a future effectiveness trial.Methods The study setting was a single, urban primary care office. Patients with BMI ≥ 27 and ≥ 1 cardiovascular risk factor were sent a single electronic health record (EHR) message between December 2019 and January 2020 offering services to support an initial weight loss goal of about “10 pounds in 10 weeks.” All patients who affirmed weight loss interest were pragmatically enrolled in the trial and offered “Basic Lifestyle Services” (BLS), including a scale that transmits weight data to the EHR using cellular networks, a coupon to enroll in lifestyle coaching resources through a partnering fitness organization, and periodic EHR messages encouraging use of these resources. About half (n = 42) of participants were randomized by an automated EHR algorithm to also receive “Customized Lifestyle Services” (CLS), including weekly email messages adapted to individual weight loss progress and telephonic coaching by a nurse for those facing challenges. Interventions and assessments spanned January to July 2020, with interference by the coronavirus pandemic. Weight measures were collected from administrative sources. Qualitative analysis of stakeholder recommendations and patient interviews assessed acceptability, appropriateness, and sustainability of intervention components.Results Over 6 weeks, 426 patients were sent the EHR invitation message and 80 (18.8%) affirmed interest in the weight loss goal and were included for analysis. EHR data were available to ascertain a 6-month weight value for 77 (96%) patients. Overall, 62% of participants lost weight; 15.0% exhibited weight loss ≥ 5%, with no statistically significant difference between CLS or BLS arms (p = 0.85). CLS assignment increased participation in daily self-weighing (43% versus 21% of patients through 12 weeks) and enrollment in referral-based lifestyle support resources (52% versus 37%).Conclusions This preliminary study demonstrates feasibility of implementation strategies for primary care offices to offer and coordinate ILI core components, as well as a pragmatic randomization procedure for use in a future randomized comparative trial.

Broadly neutralizing antibodies target the coronavirus fusion peptide (preprint)

The potential for future coronavirus outbreaks highlights the need to develop strategies and tools to broadly target this group of pathogens. Here, using an epitope-agnostic approach, we identified six monoclonal antibodies that bound to spike proteins from all seven human-infecting coronaviruses. Epitope mapping revealed that all six antibodies target the conserved fusion peptide region adjacent to the S2' cleavage site. Two antibodies, COV44-62 and COV44-79, broadly neutralize a range of alpha and beta coronaviruses, including SARS-CoV-2 Omicron subvariants BA.1 and BA.2, albeit with lower potency than RBD-specific antibodies. In crystal structures of Fabs COV44-62 and COV44-79 with the SARS-CoV-2 fusion peptide, the fusion peptide epitope adopts a helical structure and includes the arginine at the S2' cleavage site. Importantly, COV44-79 limited disease caused by SARS-CoV-2 in a Syrian hamster model. These findings identify the fusion peptide as the target of the broadest neutralizing antibodies in an epitope-agnostic screen, highlighting this site as a candidate for next-generation coronavirus vaccine development.