Coronavirus disease 2019 (COVID-19) in humans is often a clinically mild illness, but some individuals develop severe pneumonia, respiratory failure and death
. Studies of severe acute respiratory ...syndrome coronavirus 2 (SARS-CoV-2) infection in hamsters
and nonhuman primates
have generally reported mild clinical disease, and preclinical SARS-CoV-2 vaccine studies have demonstrated reduction of viral replication in the upper and lower respiratory tracts in nonhuman primates
. Here we show that high-dose intranasal SARS-CoV-2 infection in hamsters results in severe clinical disease, including high levels of virus replication in tissues, extensive pneumonia, weight loss and mortality in a subset of animals. A single immunization with an adenovirus serotype 26 vector-based vaccine expressing a stabilized SARS-CoV-2 spike protein elicited binding and neutralizing antibody responses and protected against SARS-CoV-2-induced weight loss, pneumonia and mortality. These data demonstrate vaccine protection against SARS-CoV-2 clinical disease. This model should prove useful for preclinical studies of SARS-CoV-2 vaccines, therapeutics and pathogenesis.
The COVID-19 pandemic has led to extensive morbidity and mortality throughout the world. Clinical features that drive SARS-CoV-2 pathogenesis in humans include inflammation and thrombosis, but the ...mechanistic details underlying these processes remain to be determined. In this study, we demonstrate endothelial disruption and vascular thrombosis in histopathologic sections of lungs from both humans and rhesus macaques infected with SARS-CoV-2. To define key molecular pathways associated with SARS-CoV-2 pathogenesis in macaques, we performed transcriptomic analyses of bronchoalveolar lavage and peripheral blood and proteomic analyses of serum. We observed macrophage infiltrates in lung and upregulation of macrophage, complement, platelet activation, thrombosis, and proinflammatory markers, including C-reactive protein, MX1, IL-6, IL-1, IL-8, TNFα, and NF-κB. These results suggest a model in which critical interactions between inflammatory and thrombosis pathways lead to SARS-CoV-2-induced vascular disease. Our findings suggest potential therapeutic targets for COVID-19.
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•SARS-CoV-2 infection leads to macrophage infiltrates in the lung of infected macaques•SARS-CoV-2 upregulates proinflammatory cytokines and ISGs in macaques•SARS-CoV-2 upregulates complement and coagulation cascade in macaques•SARS-CoV-2 infection leads to endothelial damage and thrombosis in macaques
Aid et al. show that SARS-CoV-2 causes endothelial disruption and vascular thrombosis in both human and rhesus macaques lungs by inducing an upregulation of proinflammatory cytokines. Using an approach that combines histopathology and multiomics in macaques, they show the progression to vascular disease over time, which involves complement, macrophage, cytokine, and thrombosis cascades.
Coconut water is widely consumed and appreciated due its sensory, nutritional, and functional characteristics. Despite being widely consumed, this beverage has a short shelf life that can be improved ...through processing technologies including non-thermal technologies. Although this processing is promising, it also can generate toxic bioactive compounds of natural and synthetic origin. Their safety has been long discussed, and concern for human food security is now clearly manifested by warnings added on products labels. The aim of this work was to evaluate the toxic and the protective effect of natural and processed coconut water by non-thermal technologies against oxidative stress in brine shrimp (
Artemia salina
). For acute toxicity test,
A. salina
nauplii instar II were exposed to different concentrations and ozone-processed (OTCW), plasma-processed (PTCW), and ultrasound-processed (UTCW) coconut water. The non-processed sample was the negative control. By the end of experiment (48 h), dead nauplii were counted and investigated under optical and electron microscopy. The protective effect was evaluated against H
2
O
2
and morphological changes were also investigated. Coconut water treated with plasma and ultrasound was not toxic to
Artemia salina
nauplii at 10, 100, or 1000 μg mL
−1
; however, ozone-treated artificial seawater caused a mild toxicity to nauplii exposed to 1000 μg mL
−1
. All coconut water samples, included untreated samples, presented protective effect against oxidative stress caused by H
2
O
2
reaching levels of 87.5% protection compared to control (24 h of experiment).
One of the main drawbacks of drying fruits is the degradation of their quality by oxidative processes. In this study, antioxidant pectin coatings were prepared and applied onto kiwi slices before the ...drying process to evaluate their effect on drying kinetics, on maintaining nutritional quality and antioxidant capacity of the cut fruit, and during 31 days of storage. Pectin antioxidant coating formulations have been developed by adding antioxidant extracts from fruits or antioxidant acids. Uncoated dehydrated fruits and those coated with pectin without antioxidants were used as control. Convective drying was carried out, desorption isotherms (30, 50 and 60°C) and drying kinetics (50 and 60°C) were analyzed, and the obtained experimental data were adjusted to the GAB and Page models, respectively. The dried kiwi slices were evaluated for their retention of antioxidants (vitamin C and phenolic compounds), total antioxidant activity (DPPH), mechanical properties, and color. The coatings had a slight influence on the isotherms and drying kinetics at the studied temperatures, mainly for the one performed at 30°C. However, the drying rate at 60°C decreased more rapidly and the Page model fit well with the experimental data. The antioxidant coatings preserved the thermosensitive compounds during drying, and formulations with the acerola extract and antioxidant acids may be highlighted since, in addition to the antioxidant effect, they also nutritionally enriched the kiwi slices. Thus, the proposed methodology is a promising technique to reduce the oxidative effects inherent in the drying and storage processes.
Antibody therapeutic strategies have served an important role during the COVID-19 pandemic, even as their effectiveness has waned with the emergence of escape variants. Here we sought to determine ...the concentration of convalescent immunoglobulin required to protect against disease from SARS-CoV-2 in a Syrian golden hamster model.
Total IgG and IgM were isolated from plasma of SARS-CoV-2 convalescent donors. Dose titrations of IgG and IgM were infused into hamsters 1 day prior to challenge with SARS-CoV-2 Wuhan-1.
The IgM preparation was found to have ~25-fold greater neutralization potency than IgG. IgG infusion protected hamsters from disease in a dose-dependent manner, with detectable serum neutralizing titers correlating with protection. Despite a higher
neutralizing potency, IgM failed to protect against disease when transferred into hamsters.
This study adds to the growing body of literature that demonstrates neutralizing IgG antibodies are important for protection from SARS-CoV-2 disease, and confirms that polyclonal IgG in sera can be an effective preventative strategy if the neutralizing titers are sufficiently high. In the context of new variants, against which existing vaccines or monoclonal antibodies have reduced efficacy, sera from individuals who have recovered from infection with the emerging variant may potentially remain an efficacious tool.
El objetivo de este estudio era analizar las publicaciones científicas sobre la influencia de los agentes sociales en el deporte con el fin de identificar los distintos tipos (emocional, informativo, ...tangible) y niveles (positivo, indiferente, negativo) de apoyo social que brindan a los deportistas sus familiares, entrenadores y compañeros de equipo. Esta investigación sistemática se llevó a cabo mediante la búsqueda en las bases de datos de PsycInfo, ProQuest, SportDiscus, Scopus y Web of Science, así como en listas de revisiones sistemáticas del apoyo social al deporte. Para llevar a cabo el estudio se utilizó la lista de comprobación PRISMA y el análisis de calidad del estudio se implementó aplicando la declaración STROBE. Se usaron los criterios PECOS para evaluar la elegibilidad de los estudios encontrados a partir de los términos aplicados en la estrategia de búsqueda. Los 31 estudios seleccionados examinaban la percepción de los deportistas de modalidades individual y colectiva de las tres etapas del entrenamiento deportivo (diversificación, especialización e inversión). La conclusión principal es que los avances en la investigación sobre el apoyo social han generado un conjunto diverso de pruebas que revelan que el análisis se enfoca principalmente en el apoyo social familiar. Se identificó que los familiares acostumbran a ser los principales proveedores de apoyo social y, como tales, ofrecen a los deportistas formas únicas de apoyo emocional, informativo e intangible tanto desde una perspectiva positiva como negativa. Los entrenadores desempeñan un papel importante en el apoyo emocional e informativo y los compañeros de equipo, en el apoyo emocional. La conclusión es que contar con unos niveles positivos de apoyo emocional, informativo y tangible por parte de los agentes sociales es fundamental para consolidar la voluntad de los deportistas de mantener y prolongar su implicación con el deporte.
A COVID-19 vaccine that can give early protection is needed to eliminate the viral spread efficiently. Here, we demonstrate the development of a nanoparticle vaccine candidate, REVC-128, in which ...multiple trimeric spike ectodomains with glycine (G) at position 614 were multimerized onto a nanoparticle. In-vitro characterization of this vaccine confirms its structural and antigenic integrity. In-vivo immunogenicity evaluation in mice indicates that a single dose of this vaccine induces potent serum neutralizing antibody titre at two weeks post-immunization. This is significantly higher than titre caused by trimeric spike protein without nanoparticle presentation. The comparison of serum binding to spike subunits between animals immunized by a spike with and without nanoparticle presentation indicates that nanoparticle prefers the display of spike RBD (Receptor-Binding Domain) over S2 subunit, likely resulting in a more neutralizing but less cross-reactive antibody response. Moreover, a Syrian golden hamster in-vivo model for the SARS-CoV-2 virus challenge was implemented two weeks post a single dose of REVC-128 immunization. The results showed that vaccination protects hamsters against the SARS-CoV-2 virus challenge with evidence of steady body weight, suppressed viral loads and alleviation of tissue damage for protected animals, compared with ∼10% weight loss, high viral loads and tissue damage in unprotected animals. Furthermore, the data showed that vaccine REVC-128 is thermostable at up to 37°C for at least 4 weeks. These findings, along with a history of safety for protein vaccines, suggest that the REVC-128 is a safe, stable and efficacious single-shot vaccine to give the earliest protection against SARS-CoV-2 infection.
O objetivo deste estudo descritivo foi analisar a associação entre autoeficácia no Ensino Superior e a satisfação acadêmica de estudantes universitários em Educação Física. Participaram 251 ...universitários matriculados nos cursos de Licenciatura e Bacharelado em Educação Física de uma universidade pública do estado de Santa Catarina/Brasil. Para a coleta de dados, foram utilizadas a Escala de Autoeficácia no Ensino Superior e a Escala de Satisfação com Experiências Acadêmicas. Os dados foram processados utilizando recursos estatísticos descritivos e inferenciais no software SPSS, versão 25.0. Os resultados mostraram escores médios superiores a sete em todas as dimensões da autoeficácia, com destaque para as dimensões social e gestão. Especificamente, quanto mais o aluno se percebe autoeficaz, mais satisfeito ele fica com a instituição. As evidências ressaltam a importância de pesquisas focadas na relação entre autoeficácia acadêmica e satisfação de estudantes do Ensino Superior para a melhoria da qualidade dos cursos ofertados.
SARS-CoV-2 is the third pathogenic coronavirus to emerge since 2000. Experience from prior outbreaks of SARS-CoV and MERS-CoV has demonstrated the importance of both humoral and cellular immunity to ...clinical outcome, precepts that have been recapitulated for SARS-CoV-2. Despite the unprecedented rapid development and deployment of vaccines against SARS-CoV-2, more vaccines are needed to meet global demand and to guard against immune evasion by newly emerging SARS-CoV-2 variants. Here we describe the development of pGO-1002, a novel bi-cistronic synthetic DNA vaccine that encodes consensus sequences of two SARS-CoV-2 antigens, Spike and ORF3a. Mice immunized with pGO-1002 developed humoral and cellular responses to both antigens, including antibodies and capable of neutralizing infection by a clinical SARS-CoV-2 isolate. Rats immunized with pGO-1002 by intradermal (ID) injection followed by application of suction with our GeneDerm device also developed humoral responses that included neutralizing antibodies and RBD-ACE2 blocking antibodies as well as robust cellular responses to both antigens. Significantly, in a Syrian hamster vaccination and challenge model, ID+GeneDerm-assisted vaccination prevented viral replication in the lungs and significantly reduced viral replication in the nares of hamsters challenged with either an ancestral SARS-CoV-2 strain or the B.1.351 (Beta) variant of concern. Furthermore, vaccinated immune sera inhibited virus-mediated cytopathic effects
in vitro.
These data establish the immunogenicity of the SARS-CoV-2 vaccine candidate pGO-1002 which induces potent humoral and cellular responses to the Spike and ORF3a antigens and may provide greater protection against emerging variants.
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