Simple virus-free mouse models of COVID-19 pathologies and oral therapeutic intervention.

The paucity of preclinical models that recapitulate COVID-19 pathology without requiring SARS-COV-2 adaptation and humanized/transgenic mice limits research into new therapeutics against the frequently emerging variants-of-concern. We developed virus-free models by C57BL/6 mice receiving oropharyngeal instillations of a SARS-COV-2 ribo-oligonucleotide common in all variants or specific to Delta/Omicron variants, concurrently with low-dose bleomycin. Mice developed COVID-19-like lung pathologies including ground-glass opacities, interstitial fibrosis, congested alveoli, and became moribund. Lung tissues from these mice and bronchoalveolar lavage and lung tissues from patients with COVID-19 showed elevated levels of hyaluronic acid (HA), HA-family members, an inflammatory signature, and immune cell infiltration. 4-methylumbelliferone (4-MU), an oral drug for biliary-spasm treatment, inhibits HA-synthesis. At the human equivalent dose, 4-MU prevented/inhibited COVID-19-like pathologies and long-term morbidity; 4-MU and metabolites accumulated in mice lungs. Therefore, these versatile SARS-COV-2 ribo-oligonucleotide oropharyngeal models recapitulate COVID-19 pathology, with HA as its critical mediator and 4-MU as a potential therapeutic for COVID-19.

Community-based participatory research to guide adoption of culturally responsive trauma-informed HIV care throughout Nashville, Tennessee.

Background: Psychological trauma is a highly prevalent driver of poor health among people with HIV (PWH) in the Southern United States (U.S.). Trauma-informed care (TIC) has potential to advance national Ending the HIV Epidemic (EHE) goals, but formative research is needed to tailor TIC implementation to complex and interdependent HIV networks. Methods: We applied a community-based participatory research (CBPR) approach to iteratively engage personnel from high volume HIV care institutions in Nashville, Tennessee. Current practices and potential implementation determinants were identified through participatory process mapping (PM) and key informant interviews. The Consolidated Framework for Implementation Research (CFIR) was applied to deductively code interview data. Personnel attending a dissemination summit developed a network-wide implementation plan. Results: Data were collected with personnel from five institutions (e.g., community-based organizations, primary care clinics, public health department), for PM (n=48), interviews (n=35), and the summit (n=17). Results suggest there are limited trauma screenings, assessments, and services across the network. Relevant Characteristics of Individuals included a trauma-sensitive workforce committed to continuous learning and TIC adoption. Relevant Inner Setting Factors were networks and communications, with strong tension for change, high compatibility with TIC, and need for advancing cultural responsiveness. Relevant Outer Setting Factors included patient needs and resources and cosmopolitanism, with need for better leveraged mental health services. Relevant Process domains were champions and leadership, with need to diversify championship among leaders. Relevant Intervention Characteristics included relative advantage and complexity, with need for personnel wellness initiatives and increased engagement with the community as service designers. Four recommendations included development of shared communication systems, personnel wellness campaigns, routine evaluations to inform practices, and culturally responsive care initiatives. Conclusion: Modifiable TIC determinants were identified, and a community-created implementation plan was developed to guide adoption. Future research will focus on city-wide implementation and strengthening pre-implementation research in other settings.