SmRNA PRIME S+N DNA BOOST VACCINATION ELICITS ROBUST IMMUNE RESPONSES in MICE

Background: Currently available COVID-19 vaccination regimens in the US deliver either a homologous spike (S) mRNA prime-boost or a prime-only S DNA adenovirus-vectored antigen to elicit humoral and cell-mediated responses to confer protection against SAR-CoV-2 infection. Alternatively, heterologous vaccination using two different platforms has the potential to enhance and expand immune protection. Addition of a second SARS-CoV-2 antigen, the nucleocapsid (N) protein that is less subject to mutation and elicits vigorous T-cell responses, may also be advantageous. We report immunological responses to homologous and heterologous prime-boost vaccination regimens with a human DNA adenovirus serotype 5 S plus N (AdS+N) and/or a self-amplifying S-only mRNA vaccine (AAAH) delivered with a nanostructured lipid carrier (NLC). Methods: CD-1 mice received homologous or heterologous prime-boost combinations of AdS+N and AAAH. Priming doses were administered on Day 0, booster doses were delivered on Day 21, and mice were euthanized for blood and organ collection on Day 35. Serum was analyzed for anti-S (both wild type and variant) and anti-N IgG subtypes by ELISA. Spleen-resident CD4+ and CD8+ T cells were tested for IFN-γ, TNF-α, and IL-2 production in response to S-WT, S Delta variant and N protein overlapping peptides by intracellular cytokine staining (ICS). Splenocyte cytokine secretion upon stimulation with S-WT/N peptides was also assessed by IFN-γ and IL-4 ELISpot. Serum neutralization of the original Wuhan strain, Delta, and B.1.351 variants was assessed by a pseudovirus neutralization assay. Results: The highest humoral and T-cell responses were seen with the heterologous AAAH prime-AdS+N boost regimen, with a significant increase in T-cell responses relative to homologous vaccination. S protein-binding IgG was similar between wild type and Delta variant S proteins, with a strong/clear Th1/Th2 bias, and T cells responded to S wild type and S Delta peptides with similar levels of cytokine expression. Sera from AAAH prime-AdS+N boost mice showed the ability to neutralize Wuhan D614G, Delta, and B.1.351 (South Africa) variant pseudoviruses at high levels. Conclusion: Heterologous vaccination with the AAAH RNA vaccine prime and an AdS+N DNA boost may provide substantially improved humoral and cell-based immunity against SARS-CoV-2 variants by leveraging the advantages of each vaccine platform technology and by inclusion of immune responses to N.

A qualitative needs assessment of covid-19's impact on em interns

Learning Objectives: To characterize the impact that COVID-19 has had on the well-being and educational experience of EM interns in 2020 Background: The COVID-19 pandemic posed an unprecedented challenge to our learners. EM interns this year began their training during a time of great need and with less clinical experience than those of prior years. Objectives: To characterize the impact that COVID-19 has had on the well-being and educational experience of EM interns in 2020. Methods: We conducted a 60-minute semi-structured focus group with 18 interns at a single residency program in July 2020. A recording of the interview was transcribed and de-identified. Using qualitative methods, initial coding was performed independently using an inductive and iterative process by two study authors with experience in qualitative methodology. Once saturation was achieved, final codes were re-applied by an initial coder and a third author. After consensus discussion, agreement reached 100%, and codes were grouped for thematic analysis. Results: We identified two major themes: education and professional identity formation. Interns expressed concerns about the quality and breadth of their medical training during COVID. Interns also voiced frustration with the politicization of medicine and uncertainty about their roles as physicians during the pandemic. Minor themes included physical health, mental health, and grief related to COVID-19. Conclusions: Our analysis suggests that new EM interns have significant concerns about their medical knowledge and the quality of their education as well as their identity as emergency physicians and public health advocates. These results may inform future decisions regarding dedicated support and training necessary for this unique group of learners.

A Qualitative Needs Assessment of COVID-19's Impact on Emergency Medicine Interns

Study Objective: The COVID-19 pandemic posed an unprecedented challenge to our learners. Emergency medicine interns this year began their training during a time of great need for skilled medical professionals and with less clinical experience than those of prior years. Methods: We conducted a 60-minute semi-structured focus group with 18 EM interns at a single residency program in July 2020. A recording of the interview was transcribed and de-identified. Using qualitative methods, initial coding was performed independently using an inductive and iterative process by two study authors with experience in qualitative methodology. Once saturation was achieved, final codes were re-applied by an initial coder and a third author. After consensus discussion, agreement reached 100%, and codes were grouped for thematic analysis. Results: We identified two major themes: education and professional identity formation. Interns expressed concerns about the quality and breadth of their medical training during the COVID pandemic. Interns also voiced frustration with the politicization of medicine and uncertainty about their roles as physicians and public health advocates during the pandemic. Minor themes included physical health, mental health, and grief related to COVID-19. Interns reported experiencing several unique challenges to their emotional and mental health, including socially distancing during a period in their training when they traditionally rely on additional support systems and build new relationships. Conclusions: Our analysis suggests that new EM interns have significant concerns about their medical knowledge and the quality of their education as well as their identity as emergency physicians and public health advocates during the COVID pandemic. EM interns also reported unique challenges to their physical and mental health. These results may inform future decisions regarding dedicated support and training necessary for this unique group of learners. [Formula presented]