Overexpression of estrogen receptor GPER1 and G1 treatment reduces SARS-CoV-2 infection in BEAS-2B bronchial cells.

Gender-bias in COVID-19 severity has been suggested by clinical data. Experimental data in cell and animal models have demonstrated the role of sex hormones, particularly estrogens, in viral infections such as in COVID-19. SARS-CoV-2 uses ACE2 as a receptor to recognize host cells, and the protease TMPRSS2 for priming the Spike protein, facilitating virus entry into cells. However, the involvement of estrogenic receptors in SARS-CoV-2 infection are still being explored. Thus, in order to investigate the role of estrogen and its receptors in COVID-19, the estrogen receptors ERα, ERß and GPER1 were overexpressed in bronchial BEAS-2B cell, and then infected with SARS-CoV-2. Interestingly, the levels of ACE2 and TMPRSS2 mRNA were higher in SARS-CoV-2-infected cells, but no difference was observed in cells with estrogen receptors overexpression. GPER1 can be involved in virus infection or replication, since its higher levels reduces SARS-CoV-2 load. On the other hand, pharmacological antagonism of GPER1 enhanced viral load. Those data suggest that GPER1 has an important role in SARS-CoV-2 infection.

Testing fractional doses of COVID-19 vaccines.

Due to the enormous economic, health, and social costs of the COVID-19 pandemic, there are high expected social returns to investing in parallel in multiple approaches to accelerating vaccination. We argue there are high expected social returns to investigating the scope for lowering the dosage of some COVID-19 vaccines. While existing evidence is not dispositive, available clinical data on the immunogenicity of lower doses combined with evidence of a high correlation between neutralizing antibody response and vaccine efficacy suggests that half or even quarter doses of some vaccines could generate high levels of protection, particularly against severe disease and death, while potentially expanding supply by 450 million to 1.55 billion doses per month, based on supply projections for 2021. An epidemiological model suggests that, even if fractional doses are less effective than standard doses, vaccinating more people faster could substantially reduce total infections and deaths. The costs of further testing alternative doses are much lower than the expected public health and economic benefits. However, commercial incentives to generate evidence on fractional dosing are weak, suggesting that testing may not occur without public investment. Governments could support either experimental or observational evaluations of fractional dosing, for either primary or booster shots. Discussions with researchers and government officials in multiple countries where vaccines are scarce suggests strong interest in these approaches.

Testing Fractional doses of COVID-19 Vaccines

Due to the enormous economic, health, and social costs of the COVID-19 pandemic, there are high expected social returns to investing in parallel in multiple approaches to accelerating vaccination. We argue there are high expected social returns to investigating the scope for lowering the dosage of some COVID-19 vaccines. While existing evidence is not dispositive, available clinical data on the immunogenicity of lower doses combined with evidence of a high correlation between neutralizing antibody response and vaccine efficacy suggests that half- or even quarter-doses of some vaccines could generate high levels of protection, particularly against severe disease and death, while potentially expanding supply by 450 million to 1.55 billion doses per month, based on supply projections for 2021. An epidemiological model suggests that even if fractional doses are less effective than standard doses, vaccinating more people faster could substantially reduce total infections and deaths. The costs of further testing alternative doses are much lower than the expected public health and economic benefits. However, commercial incentives to generate evidence on fractional dosing are weak, suggesting that testing may not occur without public investment. Governments could support either experimental or observational evaluations of fractional dosing, for either primary or booster shots. Discussions with researchers and government officials in multiple countries where vaccines are scarce suggest strong interest in these approaches.

Could Vaccine Dose Stretching Reduce COVID-19 Deaths?

We argue that alternative COVID-19 vaccine dosing regimens could potentially dramatically accelerate global COVID-19 vaccination and reduce mortality, and that the costs of testing these regimens are dwarfed by their potential benefits. We first use the high correlation between neutralizing antibody response and efficacy against disease (Khoury et. al. 2021) to show that half or even quarter doses of some vaccines generate immune responses associated with high vaccine efficacy. We then use an SEIR model to estimate that under these efficacy levels, doubling or quadrupling the rate of vaccination by using fractional doses would dramatically reduce infections and mortality. Since the correlation between immune response and efficacy may not be fully predictive of efficacy with fractional doses, we then use the SEIR model to show that fractional dosing would substantially reduce infections and mortality over a wide range of plausible efficacy levels. Further immunogenicity studies for a range of vaccine and dose combinations could deliver outcomes in weeks and could be conducted with a few hundred healthy volunteers. National regulatory authorities could also decide to test efficacy of fractional dosing in the context of vaccination campaigns based on existing immune response data, as some did for delayed second doses. If efficacy turned out to be high, the approach could be implemented broadly, while if it turned out to be low, downside risk could be limited by administering full doses to those who had received fractional doses. The SEIR model also suggests that delaying second vaccine doses will likely have substantial mortality benefits for multiple, but not all, vaccine-variant combinations, underscoring the importance of ongoing surveillance. Finally, we find that for countries choosing between approved but lower efficacy vaccines available immediately and waiting for mRNA vaccines, using immediately available vaccines typically reduces mortality.

The Universidade Federal do Rio Grande do Norte Medicine Course Mentoring Program: Integrative Activities in Focus / Programa de Mentoria do Curso de Medicina da Universidade Federal do Rio Grande do Norte: Atividades Integrativas em Foco

Resumo: Introdução: Ao ingressarem no curso de Medicina, os estudantes se deparam com desafios inerentes à formação que podem ser geradores de estresse e ansiedade, comprometendo seu bem-estar e desempenho acadêmico. Diante disso, o curso de Medicina da Universidade Federal do Rio Grande do Norte (UFRN) implantou em 2015 um programa de mentoria que se propõe a contribuir para o desenvolvimento profissional e pessoal do estudante, adotando-se como um diferencial a realização de atividades integrativas. Método: Participam desse programa 25 professores do curso de Medicina da UFRN, que atuam como mentores, 25 monitores ou mentores juniores, que têm o papel de intermediar a comunicação entre os participantes, como também auxiliar no planejamento e desenvolvimento das atividades, e 317 alunos de diversos períodos do curso médico. Além dos encontros mensais regulares, no final de cada semestre, os mentores e mentores juniores organizam a atividade integrativa que agrega todos os discentes e docentes do programa e possibilitam a construção de uma relação mais próxima entre mentores e mentorandos, bem como contribuem para a estruturação de um ambiente universitário mais acolhedor e equânime. Resultado: Em avaliação on-line sobre o programa, os alunos destacaram a "troca de experiências, de sugestões e a ajuda no curso sobre diversos temas" e "adquirir experiência de um profissional experiente" como principais motivações para participar da atividade. Contudo, enfatizaram a falta de tempo para conciliar os encontros com as demais atividades acadêmicas como principal obstáculo para participar do programa. Com a pandemia da Covid-19, mantiveram-se as atividades do programa no modelo on-line, e obteve-se importante engajamento dos participantes, o que representou uma estratégia de enfrentamento do isolamento social e de promoção da saúde mental para os estudantes. Conclusão: Observamos, a partir do engajamento e dos feedbacks recebidos, que o programa, apesar de apresentar alguns desafios, vem se configurando como uma iniciativa capaz de transformar as relações interpessoais entre discentes e mentores, ao promover a integração entre alunos dos diferentes períodos do curso e criar um ambiente favorável ao diálogo e à construção do conhecimento.

Abstract: Introduction: Upon starting their medical course, students are faced with challenges inherent to training, which can generate stress and anxiety, compromising their well-being and academic performance. In view of this, in 2015 the Medicine course at the Federal University of Rio Grande do Norte (UFRN) implemented a Mentoring Program, which aims to contribute to students' professional and personal development, focusing on integrative activities to strengthen bonds between the participants. Method: This program involves the participation of 25 professors from the UFRN Medicine course, who act as mentors, 25 monitors or mentors, who have the role of mediating communication between participants and assisting in the planning and development of activities; and about 317 students and various academic periods of the medical course. In addition to the regular monthly meetings, at the end of each semester, mentors and junior mentors organize the integrative activity that brings together all the students and teachers of the program and have stimulated a closer relationship between mentors and mentees, as well as contributing toward the structuring of a more welcoming and equitable university environment. Result: In an online assessment of the program, students highlighted the "exchange of experiences, suggestions and help with the course on various topics" and "acquiring experience from an experienced professional" as the main motivations for participating in the activity. On the other hand, they emphasized the lack of time to reconcile meetings with other academic activities as the main obstacle to participating in the program. With the onset of the Covid-19 pandemic, the program activities continued online and important engagement was achieved among the participants, thus constituting a strategy to face social isolation and promote the mental health of undergraduate medical students. Conclusion: From the engagement and the feedback received, it was observed that the program, despite presenting some challenges, represents an initiative capable of transforming interpersonal relationships between students and mentors, promoting integration between students from different academic periods of the course and creating a favourable environment for dialogue and knowledge construction.