T Cell Activation, Highly Armed Cytotoxic Cells and a Shift in Monocytes CD300 Receptors Expression Is Characteristic of Patients With Severe COVID-19.

COVID-19 manifests with a wide diversity of clinical phenotypes characterized by dysfunctional and exaggerated host immune responses. Many results have been described on the status of the immune system of patients infected with SARS-CoV-2, but there are still aspects that have not been fully characterized or understood. In this study, we have analyzed a cohort of patients with mild, moderate and severe disease. We performed flow cytometric studies and correlated the data with the clinical characteristics and clinical laboratory values of the patients. Both conventional and unsupervised data analyses concluded that patients with severe disease are characterized, among others, by a higher state of activation in all T cell subsets (CD4, CD8, double negative and T follicular helper cells), higher expression of perforin and granzyme B in cytotoxic cells, expansion of adaptive NK cells and the accumulation of activated and immature dysfunctional monocytes which are identified by a low expression of HLA-DR and an intriguing shift in the expression pattern of CD300 receptors. More importantly, correlation analysis showed a strong association between the alterations in the immune cells and the clinical signs of severity. These results indicate that patients with severe COVID-19 have a broad perturbation of their immune system, and they will help to understand the immunopathogenesis of COVID-19.

Evolución del consumo de antifúngicos en pacientes críticos. Estudio multicéntrico observacional, 2006-2010 / Trends in systemic antifungal use in critically ill patients. Multicenter observational study, 2006-2010

Hay poca información sobre el consumo de antifúngicos (AF) en pacientes críticos y las variaciones temporales desde la introducción de nuevos AF. Este consumo puede tener influencia en la aparición de resistencias. Métodos Estudio observacional prospectivo del consumo de AF sistémicos en pacientes ingresados en unidades de cuidados intensivos (UCI) españolas del registro ENVIN-HELICS durante los años 2006 a 2010. Se compara la utilización anual, el consumo según prescripciones y para infecciones intra-UCI, el calculado por tamaño de hospital y por 1.000 días de estancia. Resultados De 8.240 prescripciones de AF registradas, los AF más frecuentemente empleados fueron el fluconazol y la caspofungina (55 y 19,5%, respectivamente). Existió un incremento del consumo hasta el año 2008 y una estabilización posterior. Anualmente, se comprobó la disminución del uso de fluconazol y el crecimiento del consumo de equinocandinas. Predominó la utilización de fluconazol en hospitales de tamaño mediano con respecto a hospitales grandes (60,4% versus 53,3%; p=0,036), y lo contrario con respecto a la utilización de caspofungina (15,8% versus 21,8%; p<0,001). El fluconazol se empleó más precozmente (mediana desde el ingreso en UCI: 12 días) y durante un tiempo similar a otros AF (mediana: 8 días). El total de días de tratamiento fue de 39,51 días por 1.000 estancias, con predominio de fluconazol (21,48 días por 1.000 estancias).Conclusiones El fluconazol es el AF más utilizado en pacientes críticos en cualquiera de las indicaciones, aunque se constata un progresivo descenso en su consumo y un incremento proporcional del empleo de equinocandinas (AU)

Introduction: There are limited data about the use of antifungal agents (AF) in critically ill patients and treatment trends since the inclusion of the new generation AF. The use of these agents may have a significant influence on the development of new resistances. Methods: Observational prospective study of the systemic use of AF in patients admitted to Spanish intensive care units (ICU) participating in the ENVIN-HELICS register, from 2006 to 2010. The annual use, the indications that led to that use and, the intra-ICU infections, the AF employment related to the hospital size, and per 1000 patients/day, were compared. Results: Of the 8240 prescriptions for AF, fluconazole and caspofungin were the most often employed (55%and 19.5%, respectively). An increase in use was observed to the year 2008, with subsequent stabilisation. A decrease in the use of fluconazole and an increase in echinocandins consumption was observed overtime. As regards the intra-ICU infections, the AF were ordered empirically in 47.9% of the indications. Fluconazole was more frequently used in medium size hospitals than in the large ones (60.4% versus 53.3%;P = .036) and the opposite occurred in the case of caspofungin (15.8% versus 21.8%; P < .001). Fluconazole was more prematurely employed (median 12 days since ICU admission) and the duration of the therapy was similar to the other AF (median 8 days). The total therapy days were 39.51 per 1000 patient/day, with predominance in fluconazole use (21.48 per 1000 patients/day).Conclusions: Fluconazole is the most used antifungal agent in critically ill patients in any of the indications, although a progressive decrease in its use is observed, with a proportional increase in the use of echinocandins (AU)

[Analysis of treatments used in infections caused by gram-positive multiresistant cocci in critically ill patients admitted to the ICU]. / Análisis de los tratamientos utilizados en las infecciones por cocos grampositivos multirresistentes en pacientes críticos ingresados en UCI.

UNLABELLED: The appearance of new antimicrobials with activity against Gram-positive multiresistant cocci and knowledge of the limitations of glycopeptides has represented an important change in the use of these antibiotics. OBJECTIVE: To analyze at the national level changes in the use of antibiotics with specific activity against Gram-positive multiresistant cocci in critically ill patients admitted to the ICU as well as the characteristics of patients treated with these agents and the forms of administration. MATERIAL AND METHODS: Retrospective cohort study of patients admitted to the ICU for more than 24 hours between 2008 and 2010 in the ENVIN-HELICS national registry. Cases were defined as patients who had received one or more of the following antibiotics: vancomycin, teicoplanin, linezolid or daptomycin. The characteristics of patients who used one or more of these agents were compared with those treated with other antibiotics. Indications and forms of use of each antibiotic were assessed. Descriptive results are presented. RESULTS: A total of 45,757 patients, 27,982 (61.2%) of whom received 63,823 antimicrobials were included in the study. In 6,368 (13.9%) patients, one or more antibiotics specifically active against Gram-positive multiresistant cocci were given. There was a predominance of the use of vancomycin and linezolid and an important increase in the prescription of daptomycin (+320%) and linezolid (+22.4%). In more than 95% of cases, linezolid and daptomycin were prescribed for the treatment of infections, whereas vancomycin and teicoplanin were used for prophylaxis in 20-25% of cases. Between 75% and 80% of indications for treating infections, antibiotics were used empirically except for daptomycin which was used as a directed treatment in 43% of the cases. Only in one third of the indications for empirical treatment, susceptible microorganisms were identified (appropriate treatment). CONCLUSIONS: The use of antibiotics with activity against Gram-positive multiresistant cocci remained stable around 14% of all indications. The use of vancomycin and linezolid predominated and there was a clear trend towards an increase in the use of daptomycin and linezolid and a decrease in the use of glycopeptides. Empirical treatments were considered appropriate in only one third of cases.

[Trends in systemic antifungal use in critically ill patients. Multicenter observational study, 2006-2010]. / Evolución del consumo de antifúngicos en pacientes críticos. Estudio multicéntrico observacional, 2006-2010.

INTRODUCTION: There are limited data about the use of antifungal agents (AF) in critically ill patients and treatment trends since the inclusion of the new generation AF. The use of these agents may have a significant influence on the development of new resistances. METHODS: Observational prospective study of the systemic use of AF in patients admitted to Spanish intensive care units (ICU) participating in the ENVIN-HELICS register, from 2006 to 2010. The annual use, the indications that led to that use and, the intra-ICU infections, the AF employment related to the hospital size, and per 1000 patients/day, were compared. RESULTS: Of the 8240 prescriptions for AF, fluconazole and caspofungin were the most often employed (55% and 19.5%, respectively). An increase in use was observed to the year 2008, with subsequent stabilisation. A decrease in the use of fluconazole and an increase in echinocandins consumption was observed over time. As regards the intra-ICU infections, the AF were ordered empirically in 47.9% of the indications. Fluconazole was more frequently used in medium size hospitals than in the large ones (60.4% versus 53.3%; P=.036) and the opposite occurred in the case of caspofungin (15.8% versus 21.8%; P<.001). Fluconazole was more prematurely employed (median 12 days since ICU admission) and the duration of the therapy was similar to the other AF (median 8 days). The total therapy days were 39.51 per 1000 patient/day, with predominance in fluconazole use (21.48 per 1000 patients/day). CONCLUSIONS: Fluconazole is the most used antifungal agent in critically ill patients in any of the indications, although a progressive decrease in its use is observed, with a proportional increase in the use of echinocandins.

Análisis de los tratamientos utilizados en las infecciones por cocos grampositivos multirresistentes en pacientes críticos ingresados en UCI / Analysis of treatments used in infections caused by Gram-positive multiresistant cocci in critically ill patients admitted to the ICU

La aparición de nuevos antibióticos activos frentes a cocos grampositivos multirresistentes (CGP-MR) y el conocimiento de las limitaciones de los glucopéptidos ha supuesto un importante cambio en las tendencias de utilización de estos antibióticos. Objetivo. Analizar las variaciones a nivel nacional en el consumo de antibióticos activos de forma específica frente a CGP-MR en pacientes críticos ingresados en UCI así como las características de los pacientes que los utilizan, y sus formas de empleo. Material y métodos. Análisis retrospectivo, de cohortes que incluye los pacientes ingresados en UCI más de 24 horas entre los años 2008-2010 del registro ENVIN-HELICS. Se define como caso los pacientes que han recibido uno o más de los siguientes antibióticos: vancomicina, teicoplanina, linezolid o daptomicina. Se comparan las características de los pacientes que han utilizado uno o más de dichos antibióticos con los pacientes que han utilizado otros antibióticos. Se describen las indicaciones y formas de utilización de cada uno de ellos. Los resultados se presentan de forma descriptiva. Resultados. Se han incluido 45.757 pacientes de los que 27.982 (61,2%) han utilizado 63.823 antimicrobianos. En 6.368 (13,9%) pacientes se han utilizado uno o más antibióticos activos de forma selectiva frente a CGP-MR. Ha predominado la utilización de vancomicina y linezolid y se observa un importante incremento en la prescripción de daptomicina (+320%) y de linezolid (+22,4%). Mas del 95% de indicaciones de linezolid y daptomicina se realizaron para el tratamiento de infecciones mientras que vancomicina y teicoplanina se utilizó entre el 20-25% de los casos para profilaxis. Entre el 75-80% de las indicaciones de tratamiento se han realizado de forma empírica excepto con daptomicina que se ha utilizado de forma dirigida en el 43% de los casos. Sólo en una tercera parte de las indicaciones para tratamiento empírico se han identificado microorganismos susceptibles (tratamiento apropiado). Conclusiones. El empleo de antibióticos activos frente a CGP-MR se mantiene estable en torno al 14% del total de indicaciones. Existe un predominio en el uso de linezolid y vancomicina y una clara tendencia a incrementar el empleo de daptomicina y linezolid y a disminuir el uso de glucopéptidos. Sólo una tercera parte de los tratamientos empíricos con estos antibióticos se han valorado como apropiados(AU)

The appearance of new antimicrobials with activity against Gram-positive multiresistant cocci and knowledge of the limitations of glycopeptides has represented an important change in the use of these antibiotics. Objetive. To analyze at the national level changes in the use of antibiotics with specific activity against Gram-positive multiresistant cocci in critically ill patients admitted to the ICU as well as the characteristics of patients treated with these agents and the forms of administration. Material and methods. Retrospective cohort study of patients admitted to the ICU for more than 24 hours between 2008 and 2010 in the ENVIN-HELICS national registry. Cases were defined as patients who had received one or more of the following antibiotics: vancomycin, teicoplanin, linezolid or daptomycin. The characteristics of patients who used one or more of these agents were compared with those treated with other antibiotics. Indications and forms of use of each antibiotic were assessed. Descriptive results are presented. Results. A total of 45,757 patients, 27,982 (61.2%) of whom received 63,823 antimicrobials were included in the study. In 6,368 (13.9%) patients, one or more antibiotics specifically active against Gram-positive multiresistant cocci were given. There was a predominance of the use of vancomycin and linezolid and an important increase in the prescription of daptomycin (+320%) and linezolid (+22.4%). In more than 95% of cases, linezolid and daptomycin were prescribed for the treatment of infections, whereas vancomycin and teicoplanin were used for prophylaxis in 20-25% of cases. Between 75% and 80% of indications for treating infections, antibiotics were used empirically except for daptomycin which was used as a directed treatment in 43% of the cases. Only in one third of the indications for empirical treatment, susceptible microorganisms were identified (appropriate treatment). Conclusions. The use of antibiotics with activity against Gram-positive multiresistant cocci remained stable around 14% of all indications. The use of vancomycin and linezolid predominated and there was a clear trend towards an increase in the use of daptomycin and linezolid and a decrease in the use of glycopeptides. Empirical treatments were considered appropriate in only one third of cases(AU)