RESUMO
Coronavirus disease 2019 (COVID-19) is characterized by a high incidence of acute respiratory failure. The underlying immunopathology of that failure and how it compares to other causes of severe respiratory distress, such as influenza virus infection, are not fully understood. Here we addressed this by developing a prospective observational cohort of COVID-19 and influenza subjects with varying degrees of disease severity and assessing the quality and magnitude of their immune responses at the cellular and protein level. Additionally, we performed single-cell RNA transcriptional profiling of peripheral blood mononuclear cells from select subjects. The cohort consists of 79 COVID-19 subjects, 26 influenza subjects, and 15 control subjects, including 35 COVID-19 and 7 influenza subjects with acute respiratory failure. While COVID-19 subjects exhibited largely equivalent or greater activated lymphocyte counts compared to influenza subjects, they had fewer monocytes and lower surface HLA-class II expression on monocytes compared to influenza subjects and controls. At least two distinct immune profiles were observed by cytokine levels in severe COVID-19 patients: 3 of 71 patients were characterized by extreme inflammation, with greater than or equal to [~]50% of the 35 cytokines measured greater than 2 standard deviations from the mean level of other severe patients (both influenza and COVID-19); the other immune profile, which characterized 68 of 71 subjects, had a mixed inflammatory signature, where 28 of 35 cytokines in COVID-19 patients had lower mean cytokine levels, though not all were statistically significant. Only 2 cytokines were higher in COVID-19 subjects compared to influenza subjects (IL-6 and IL-8). Influenza and COVID-19 patients could be distinguished statistically based on cytokine module expression, particularly after controlling for the significant effects of age on cytokine expression, but again with lower levels of most cytokines in COVID-19 subjects. Further, high circulating levels of IL-1RA and IL-6 were associated with increased odds of intubation in the combined influenza and COVID-19 cohort [OR = 3.93 and 4.30, respectively] as well as among only COVID-19 patients. Single cell transcriptional profiling of COVID-19 and influenza subjects with respiratory failure identified profound suppression in type I and type II interferon signaling in COVID-19 patients across multiple clusters. In contrast, COVID-19 cell clusters were enriched for alterations in metabolic, stress, and apoptotic pathways. These alterations were consistent with an increased glucocorticoid response in COVID-19 patients compared to influenza. When considered across the spectrum of innate and adaptive immune profiles, the immune pathologies underlying severe influenza and COVID-19 are substantially distinct. The majority of COVID-19 patients with acute respiratory failure do not have a cytokine storm phenotype but instead exhibit profound type I and type II IFN immunosuppression when compared to patients with acute influenza. Upregulation of a small number of inflammatory mediators, including IL-6, predicts acute respiratory failure in both COVID-19 and influenza patients.
RESUMO
Introducción: el uso inadecuado de los antimicrobianos es un importante factor de resistencia a estos. En medicina veterinaria, este factor puede influir en el rendimiento de los animales, como en el caso de la mastitis bovina. Objetivo: evaluar la actividad antibacteriana de los aceites esenciales e hidroalcohólicos, de Cymbopogon citratus (DC.) Stapf., Elionurus sp. y Tagetes minuta L. contra bacterias aisladas de leche bovina. Métodos: la actividad antimicrobiana de plantas se evaluó utilizando la técnica de microdilución con la determinación de la concentración inhibitoria mínima. Resultados: los aceites esenciales eran más activos que los hidroalcohólicos, con valores de concentración mínima inhibitoria entre 0,39 y 6,32; 0,10 y 6,32 %; así como de 0,62 a 5 %, para Cymbopogon citratus, Elionurus sp. y Tagetes minuta, respectivamente; mientras que en los extractos hidroalcohólicos, excepto para Tagetes minuta, solo se inhibió Streptococcus uberis con Elionurus sp., pero el extracto hidroalcohólico de Cymbopogon citratus no mostró actividad antibacteriana. Conclusiones: los resultados sugieren el uso de estas plantas como un antimicrobiano natural, que es eficaz sobre bacterias de la mastitis bovina.
Introduction: the inappropriate use of antimicrobials is a major driver of antimicrobial resistance. In veterinary medicine, this factor can influence on animal performance, as in the case of bovine mastitis. Objective: this study is aimed to evaluate the antibacterial activity of essential oils and hydroalcoholic of Cymbopogon citratus (DC.) Stapf., Elionurus sp. and Tagetes minuta L. and the bacteria isolated from bovine milk. Methods: the antimicrobial activity of plants was evaluated using the microdilution technique, determining minimum inhibitory concentration values. Results: the essential oils were more active than the hydroalcoholic, with minimum inhibitory concentration values between 6,32 to 0,39 %; 0,10 and 6,32 %; as well as 0,62 to 5 %, for Cymbopogon citratus, Elionurus and T. minuta, respectively; while EHAs, except for Tagetes minuta, only inhibited Streptococcus uberis to Elionurus sp., being that the hydroalcoholic the Cymbopogon citratus showed no antibacterial activity. Conclusions: these results suggest the use of these plants as natural antimicrobial, being effective against bacteria of bovine mastitis.
RESUMO
Introducción: la aparición de cepas bacterianas resistentes a los antibióticos ha estimulado el desarrollo de nuevas líneas de investigación, basadas en las propiedades antibacterianas de plantas utilizadas en medicina popular. La medicina veterinaria ha estado tomando para sí los beneficios de la medicina tradicional, en un intento de sustituir el uso de antibióticos en el tratamiento y la prevención de la mastitis. Objetivo: evaluar la actividad antibacteriana de los extractos hidralcohólicos de Syzygium cumini (L.) Skeels, en comparación con las bacterias relacionadas en la mastitis bovina. Métodos: se obtuvieron extractos de hojas frescas con alcohol a 92,8° y de hojas secas con alcohol a 70°. La actividad antimicrobiana de plantas se evaluó utilizando la técnica de microdilución. Resultados: los extractos de hojas frescas mostraron una actividad mejor en comparación con los de hojas secas, con valores de concentración mínima inhibitoria de 1,5 a 50 %, en comparación con los diferentes microorganismos. Se destaca como más eficaz contra todo estudio el Streptococcus, con la concentración mínima inhibitoria igual a 3,1; 1,5 y 1,9 % para Streptococcus uberis, Streptococcus agalacteae y Streptococcus dysgalacteae, respectivamente. Conclusiones: estos resultados sugieren que el uso de hojas de esta especie de planta puede constituir una alternativa viable para la prevención y el tratamiento de la mastitis bovina.
Introduction: the emergence of bacterial strains resistant to antibiotics has stimulated the development of new lines of research based on the antibacterial properties of plants used in folk medicine. Veterinary medicine has been taking for itself the benefits of traditional medicine in an attempt to replace the use of antibiotics in the treatment and prevention of mastitis. Objective: this study is aimed to evaluate the antibacterial activity of hydroalcoholic extracts Syzygium cumini (L.) Skeels, compared to bacteria related to bovine mastitis. Methods: the extracts were obtained from fresh leaves with ethanol at 92.8° and leaves with ethanol at 70°. The antimicrobial activity of plants was evaluated using the microdilution technique. Results: the hydroalcoholic extracts fresh plant showed better activity compared with the hydroalcoholic extracts dry leaf, with minimal inhibitory concentration values ranging from 1.5 to 50 % compared to the different microorganisms; highlighting Streptococcus as more effective against all study, with minimal inhibitory concentration equal to 3.1, 1.5, and 1.9 % for Streptococcus uberis, Streptococcus agalacteae, and Streptococcus dysgalacteae, respectively. Conclusions: these results suggest that the use of leaves of this plant species may constitute a viable alternative for the prevention and treatment of bovine mastitis.
RESUMO
Introducción: el sistema de producción de leche agroecológico está limitado por alternativas sostenibles de promoción a la salud animal. El control de la mastitis con plantas medicinales puede ser viable de modo económico y ecológicamente. Objetivos: evaluar la aplicación de antisépticos en la desinfección de pezones posordeño. Métodos: se comparó un convencional y extracto de plantas medicinales en un rebaño comercial y tuvo como principal encierre las nuevas infecciones intramamarias. Resultados: la prevalencia semanal del California Mastitis Test varió en el grupo 1 entre 29,5 y 17,1 por ciento, y en el grupo 2 de 29,7 a 19,6 por ciento, no diferenciándose de modo significativo, en ninguna de las semanas. La incidencia de cultura positiva para Staphylococcus/Streptococcus fue de 3,93 y 6,96/1 000 cuartos/d para los grupos 1 y 2, respectivamente; con p= 0,057. Hubo 4 casos de mastitis clínica durante el experimento, 2 en cada tratamiento. Conclusiones: el uso de extractos de plantas en la desinfección de pezones posordeño puede ser útil a los sistemas de producción de leche agroecológicos.
Introduction: the agro-ecological system of milk production is limited in terms of sustainable alternatives for animal health promotion. The control of mastitis with medicinal plants can be economically and environmentally viable. Objectives: to evaluate the use of antiseptics in the post-milking teat disinfection. Methods: the comparison of conventional and herbal extracts in treating the new intramammarial infections. Results: the weekly prevalence of California Mastitis Test ranged from 29.5 to 17.1 percent in group 1 and from 29.7 to 19.6 percent in group 2 but no significant difference was found in any week. The incidence of positive culture for Staphylococcus/Streptococcus was 3.93 and 6.96/1 000 quarters/day for groups 1 and 2 respectively, being p= 0.057. There were four cases of clinical mastitis during the experiment, two cases in each treatment. Conclusions: the use of plant extracts in the post-milking teat disinfection may be useful for agro-ecological systems of milk production.
