A self-amplifying mRNA SARS-CoV-2 vaccine candidate induces safe and robust protective immunity in preclinical models.

RNA vaccines have demonstrated efficacy against SARS-CoV-2 in humans, and the technology is being leveraged for rapid emergency response. In this report, we assessed immunogenicity and, for the first time, toxicity, biodistribution, and protective efficacy in preclinical models of a two-dose self-amplifying messenger RNA (SAM) vaccine, encoding a prefusion-stabilized spike antigen of SARS-CoV-2 Wuhan-Hu-1 strain and delivered by lipid nanoparticles (LNPs). In mice, one immunization with the SAM vaccine elicited a robust spike-specific antibody response, which was further boosted by a second immunization, and effectively neutralized the matched SARS-CoV-2 Wuhan strain as well as B.1.1.7 (Alpha), B.1.351 (Beta) and B.1.617.2 (Delta) variants. High frequencies of spike-specific germinal center B, Th0/Th1 CD4, and CD8 T cell responses were observed in mice. Local tolerance, potential systemic toxicity, and biodistribution of the vaccine were characterized in rats. In hamsters, the vaccine candidate was well-tolerated, markedly reduced viral load in the upper and lower airways, and protected animals against disease in a dose-dependent manner, with no evidence of disease enhancement following SARS-CoV-2 challenge. Therefore, the SARS-CoV-2 SAM (LNP) vaccine candidate has a favorable safety profile, elicits robust protective immune responses against multiple SARS-CoV-2 variants, and has been advanced to phase 1 clinical evaluation (NCT04758962).

Fears of disclosure and misconceptions regarding domestic violence reporting amongst patients in two US emergency departments.

Patients often do not disclose domestic violence (DV) to healthcare providers in emergency departments and other healthcare settings. Barriers to disclosure may include fears and misconceptions about whether, and under what circumstances, healthcare providers report DV to law enforcement and immigration authorities. We sought to assess undocumented Latino immigrants (UDLI), Latino legal residents/citizens (LLRC) and non-Latino legal residents/citizens (NLRC) beliefs about disclosure of DV victimization to healthcare providers and healthcare provider reporting of DV to law enforcement and immigration authorities. From 10/2018-2/2020, we conducted this survey study at two urban emergency departments (EDs) in California. Participants, enrolled by convenience sampling, responded to survey questions adapted from a previously published survey instrument that was developed to assess undocumented immigrant fears of accessing ED care. Our primary outcomes were the proportions of UDLI, LLRC and NLRC who knew of someone who had experienced DV in the past year, whether these DV victims were afraid to access ED care, reasons DV victims were afraid to access ED care, and rates of misconceptions (defined according to current California law) about the consequences of disclosing DV to healthcare providers. Of 667 patients approached, 531 (80%) agreed to participate: 32% UDLI, 33% LLRC, and 35% NLRC. Of the 27.5% of respondents who knew someone who experienced DV in the past year, 46% stated that the DV victim was afraid to seek ED care; there was no significant difference in this rate between groups. The most common fears reported as barriers to disclosure were fear the doctor would report DV to police (31%) and fear that the person perpetrating DV would find out about the disclosure (30.3%). Contrary to our hypothesis, UDLI had lower rates of misconceptions about healthcare provider and law enforcement responses to DV disclosure than LLRC and NLRC. Fear of disclosing DV and misconceptions about the consequences of disclosure of DV to healthcare providers were common, indicating a need for provider, patient, and community education and changes that lower barriers to help-seeking.

Provider and administrator-level perspectives on strategies to reduce fear and improve patient trust in the emergency department in times of heightened immigration enforcement.

STUDY OBJECTIVES: Heightened immigration enforcement may induce fear in undocumented patients when coming to the Emergency Department (ED) for care. Limited literature examining health system policies to reduce immigrant fear exists. In this multi-site qualitative study, we sought to assess provider and system-level policies on caring for undocumented patients in three California EDs. METHODS: We recruited 41 ED providers and administrators from three California EDs (in San Francisco, Oakland, and Sylmar) with large immigrant populations. Participants were recruited using a trusted gatekeeper and snowball sampling. We conducted semi-structured interviews and analyzed the transcripts using constructivist grounded theory. RESULTS: We interviewed 10 physicians, 11 nurses, 9 social workers, and 11 administrators, and identified 7 themes. Providers described existing policies and recent policy changes that facilitate access to care for undocumented patients. Providers reported that current training and communication around policies is limited, there are variations between who asks about and documents status, and there remains uncertainty around policy details, laws, and jurisdiction of staff. Providers also stated they are taking an active role in building safety and trust and see their role as supporting undocumented patients. CONCLUSIONS: This study introduces ED-level health system perspectives and recommendations for caring for undocumented patients. There is a need for active, multi-disciplinary ED policy training, clear policy details including the extent of providers' roles, protocols on the screening and documentation of status, and continual reassessment of our health systems to reduce fear and build safety and trust with our undocumented communities.