Characterization of Three Variants of SARS-CoV-2 In Vivo Shows Host-Dependent Pathogenicity in Hamsters, While Not in K18-hACE2 Mice.

Animal models are used in preclinical trials to test vaccines, antivirals, monoclonal antibodies, and immunomodulatory drug therapies against SARS-CoV-2. However, these drugs often do not produce equivalent results in human clinical trials. Here, we show how different animal models infected with some of the most clinically relevant SARS-CoV-2 variants, WA1/2020, B.1.617.2/Delta, B.1.1.529/Omicron, and BA5.2/Omicron, have independent outcomes. We show that in K18-hACE2 mice, B.1.617.2 is more pathogenic, followed by WA1, while B.1.1.529 showed an absence of clinical signs. Only B.1.1.529 was able to infect C57BL/6J mice, which lack the human ACE2 receptor. B.1.1.529-infected C57BL/6J mice had different T cell profiles compared to infected K18-hACE2 mice, while viral shedding profiles and viral titers in lungs were similar between the K18-hACE2 and the C57BL/6J mice. These data suggest B.1.1.529 virus adaptation to a new host and shows that asymptomatic carriers can accumulate and shed virus. Next, we show how B.1.617.2, WA1 and BA5.2/Omicron have similar viral replication kinetics, pathogenicity, and viral shedding profiles in hamsters, demonstrating that the increased pathogenicity of B.1.617.2 observed in mice is host-dependent. Overall, these findings suggest that small animal models are useful to parallel human clinical data, but the experimental design places an important role in interpreting the data. Importance: There is a need to investigate SARS-CoV-2 variant phenotypes in different animal models due to the lack of reproducible outcomes when translating experiments to the human population. Our findings highlight the correlation of clinically relevant SARS-CoV-2 variants in animal models with human infections. Experimental design and understanding of correct animal models are essential to interpreting data to develop antivirals, vaccines, and other therapeutic compounds against COVID-19.

Scalable live-attenuated SARS-CoV-2 vaccine candidate demonstrates preclinical safety and efficacy.

Successfully combating the COVID-19 pandemic depends on mass vaccination with suitable vaccines to achieve herd immunity. Here, we describe COVI-VAC, the only live attenuated severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine currently in clinical development. COVI-VAC was developed by recoding a segment of the viral spike protein with synonymous suboptimal codon pairs (codon-pair deoptimization), thereby introducing 283 silent (point) mutations. In addition, the furin cleavage site within the spike protein was deleted from the viral genome for added safety of the vaccine strain. Except for the furin cleavage site deletion, the COVI-VAC and parental SARS-CoV-2 amino acid sequences are identical, ensuring that all viral proteins can engage with the host immune system of vaccine recipients. COVI-VAC was temperature sensitive in vitro yet grew robustly (>107 plaque forming units/mL) at the permissive temperature. Tissue viral loads were consistently lower, lung pathology milder, and weight loss reduced in Syrian golden hamsters (Mesocricetus auratus) vaccinated intranasally with COVI-VAC compared to those inoculated with wild-type (WT) virus. COVI-VAC inoculation generated spike IgG antibody levels and plaque reduction neutralization titers similar to those in hamsters inoculated with WT virus. Upon challenge with WT virus, COVI-VAC vaccination reduced lung challenge viral titers, resulted in undetectable virus in the brain, and protected hamsters from almost all SARS-CoV-2-associated weight loss. Highly attenuated COVI-VAC is protective at a single intranasal dose in a relevant in vivo model. This, coupled with its large-scale manufacturing potential, supports its potential use in mass vaccination programs.

A Study about the Psychological Impact of COVID-19 in Medical Sciences Student from Los Palacios

RESUMEN Introducción: En estos tiempos de pandemia por la COVID- 19 se debe hacer frente a una situación inédita en nuestra sociedad, donde, además de tener que afrontar los efectos directos del virus, como pueden ser la sintomatología de la enfermedad, el miedo al contagio y la preocupación por nuestros seres queridos, también se debe lidiar con las medidas de cuarentena para frenar la pandemia. Objetivo: Describir el impacto psicológico de la COVID-19 en estudiantes de Ciencias Médicas. Métodos: Se realizó un estudio descriptivo, transversal desde abril a julio de 2020. El universo fue de 73 estudiantes y la muestra quedó conformada por 63 estudiantes que realizaron pesquisa activa en el casco urbano de Los Palacios. Se les aplicó la escala de resiliencia de Connor-Davidson y la escala para valorar el nivel de estrés. Resultados: El 79,4 % de los estudiantes mantuvo un comportamiento resiliente mientras que solo un 20,6 % mostró bajos niveles de resiliencia. El 33,3 % mantuvo niveles normales de estrés, mientras que el 66,7 % de los estudiantes presentó estrés. Conclusiones: Los estudiantes han sido un puntal indispensable para el enfrentamiento y la erradicación de la propagación de la epidemia, una vez que dieron su paso al frente para asumir la tarea de manera incondicional. No obstante, esta situación tuvo en ellos un impacto psicológico, por lo que la mayoría muestran niveles de estrés, y puntuaciones bajas en las dimensiones de resiliencia presión bajo control y espiritualidad. ABSTRACT Introduction: In these pandemic times due to COVID-19, an unprecedented situation must be confronted in our society, a scenario where, apart from having to confront the direct effects of the virus, such as the symptoms of the disease, the fear of contagion and the concern for our loved ones, we must also deal with quarantine measures to stop the pandemic. Objective: To describe the psychological impact of COVID-19 on medical sciences students. Methods: A descriptive and cross-sectional study was carried out from April to July 2020. The population consisted of 73 students and the sample was made up of 63 students who carried out active screening in the urban area of Los Palacios. They were applied the Connor-Davidson Resilience Scale and the scale for assessing their stress level. Results: 79.4% of the students maintained a resilient behavior, while only 20.6% showed low resilience levels. 33.3% maintained normal stress levels, while 6.7% of the students presented stress. Conclusions: Students have been crucial in the confrontation and eradication of epidemic spread, since the time when they stepped forward to assume the task unconditionally. However, this situation had a psychological impact on them, so most of them show stress levels and low scores in the dimensions of resilience, pressure under control, and spirituality.

A Study about the Psychological Impact of COVID-19 in Medical Sciences Student from Los Palacios

RESUMEN Introducción: En estos tiempos de pandemia por la COVID- 19 se debe hacer frente a una situación inédita en nuestra sociedad, donde, además de tener que afrontar los efectos directos del virus, como pueden ser la sintomatología de la enfermedad, el miedo al contagio y la preocupación por nuestros seres queridos, también se debe lidiar con las medidas de cuarentena para frenar la pandemia. Objetivo: Describir el impacto psicológico de la COVID-19 en estudiantes de Ciencias Médicas. Métodos: Se realizó un estudio descriptivo, transversal desde abril a julio de 2020. El universo fue de 73 estudiantes y la muestra quedó conformada por 63 estudiantes que realizaron pesquisa activa en el casco urbano de Los Palacios. Se les aplicó la escala de resiliencia de Connor-Davidson y la escala para valorar el nivel de estrés. Resultados: El 79,4 % de los estudiantes mantuvo un comportamiento resiliente mientras que solo un 20,6 % mostró bajos niveles de resiliencia. El 33,3 % mantuvo niveles normales de estrés, mientras que el 66,7 % de los estudiantes presentó estrés. Conclusiones: Los estudiantes han sido un puntal indispensable para el enfrentamiento y la erradicación de la propagación de la epidemia, una vez que dieron su paso al frente para asumir la tarea de manera incondicional. No obstante, esta situación tuvo en ellos un impacto psicológico, por lo que la mayoría muestran niveles de estrés, y puntuaciones bajas en las dimensiones de resiliencia presión bajo control y espiritualidad. ABSTRACT Introduction: In these pandemic times due to COVID-19, an unprecedented situation must be confronted in our society, a scenario where, apart from having to confront the direct effects of the virus, such as the symptoms of the disease, the fear of contagion and the concern for our loved ones, we must also deal with quarantine measures to stop the pandemic. Objective: To describe the psychological impact of COVID-19 on medical sciences students. Methods: A descriptive and cross-sectional study was carried out from April to July 2020. The population consisted of 73 students and the sample was made up of 63 students who carried out active screening in the urban area of Los Palacios. They were applied the Connor-Davidson Resilience Scale and the scale for assessing their stress level. Results: 79.4% of the students maintained a resilient behavior, while only 20.6% showed low resilience levels. 33.3% maintained normal stress levels, while 6.7% of the students presented stress. Conclusions: Students have been crucial in the confrontation and eradication of epidemic spread, since the time when they stepped forward to assume the task unconditionally. However, this situation had a psychological impact on them, so most of them show stress levels and low scores in the dimensions of resilience, pressure under control, and spirituality.