Differential Immune Checkpoint and Ig-like V-Type Receptor Profiles in COVID-19: Associations with Severity and Treatment.

Identifying patients' immune system status has become critical to managing SARS-CoV-2 infection and avoiding the appearance of secondary infections during a hospital stay. Despite the high volume of research, robust severity and outcome markers are still lacking in COVID-19. We recruited 87 COVID-19 patients and analyzed, by unbiased automated software, 356 parameters at baseline emergency department admission including: high depth immune phenotyping and immune checkpoint expression by spectral flow cytometry, cytokines and other soluble molecules in plasma as well as routine clinical variables. We identified 69 baseline alterations in the expression of immune checkpoints, Ig-like V type receptors and other immune population markers associated with severity (O2 requirement). Thirty-four changes in these markers/populations were associated with secondary infection appearance. In addition, through a longitudinal sample collection, we described the changes which take place in the immune system of COVID-19 patients during secondary infections and in response to corticosteroid treatment. Our study provides information about immune checkpoint molecules and other less-studied receptors with Ig-like V-type domains such as CD108, CD226, HVEM (CD270), B7H3 (CD276), B7H5 (VISTA) and GITR (CD357), defining these as novel interesting molecules in severe and corticosteroids-treated acute infections.

SARS-CoV-2 Proteins Induce Endotoxin Tolerance Hallmarks: A Demonstration in Patients with COVID-19.

According to a large number of reported cohorts, sepsis has been observed in nearly all deceased patients with COVID-19. We and others have described sepsis, among other pathologies, to be an endotoxin tolerance (ET)-related disease. In this study, we demonstrate that the culture of human blood cells from healthy volunteers in the presence of SARS-CoV-2 proteins induced ET hallmarks, including impairment of proinflammatory cytokine production, low MHC class II (HLA-DR) expression, poor T cell proliferation, and enhancing of both phagocytosis and tissue remodeling. Moreover, we report the presence of SARS-CoV-2 blood circulating proteins in patients with COVID-19 and how these levels correlate with an ET status, the viral RNA presence of SARS-CoV-2 in plasma, as well as with an increase in the proportion of patients with secondary infections.

Potential Role of the Galectin-9/TIM-3 Axis in the Disparate Progression of SARS-CoV-2 in a Married Couple: A Case Report.

We report the disparate clinical progression of a couple infected by SARS-CoV-2 based on their immune checkpoint (IC) levels and immune cell distribution in blood from admission to exitus in patient 1 and from admission to discharge and recovery in patient 2. A detailed clinical follow-up accompanied by a longitudinal analysis of immune phenotypes and IC levels is shown. The continuous increase in the soluble IC ligand galectin-9 (Gal-9) and the increment in T-cell immunoglobulin and mucin domain-containing 3 (TIM-3) protein in T cells in patient 1 suggests an activation of the Gal-9/TIM-3 axis and, subsequently, a potential cell exhaustion in this patient that did not occur in patient 2. Our data indicate that the Gal-9/TIM-3 axis could be a potential target in this clinical setting, along with a patent effector memory T-cell reduction.

COVID-19 in children with neuromuscular disorders.

OBJECTIVE: Children with neuromuscular disorders have been assumed to be a particularly vulnerable population since the beginning of COVID-19. Although this is a plausible hypothesis, there is no evidence that complications or mortality rates in neuromuscular patients are higher than in the general population. The aim of this study is to describe the clinical characteristics and outcome of COVID-19 in children with neuromuscular disorders. METHODS: A registry of children with neuromuscular conditions and laboratory-confirmed-SARS-CoV-2 infection was set up by the Neuromuscular Working Group of the Spanish Pediatric Neurology Society (SENEP). Data to be collected were focused on the characteristics and baseline status of the neuromuscular condition and the course of COVID-19. RESULTS: Severe complications were not observed in our series of 29 children with neuromuscular disorders infected by SARS-CoV-2. Eighty-nine percent of patients were clinically categorized as asymptomatic or mild cases and 10% as moderate cases. Patients with a relatively more severe course of COVID-19 had SMA type 1 and were between 1 and 3 years. CONCLUSIONS: The course of COVID-19 in children with neuromuscular disorders may not be as severe as expected. The protective role of young age seems to outweigh the risk factors that are common in neuromuscular patients, such as a decreased respiratory capacity or a weak cough. Further studies are needed to know if this finding can be generalized to children with other chronic diseases.

Cambios evolutivos pulmonares en la ecografía torácica en pacientes con COVID-19 / Time course of lung changes on thoracic ultrasound of mild COVID-19 patients

No disponible

Malformación congénita de seno dural con resolución espontánea / Congenital malformation of dural sinus that resolved spontaneously

No disponible

Características del líquido sinovial en pacientes con artritis idiopática juvenil / Characteristics of synovial fluid in patients with juvenile idiopathic arthritis

Introducción: El análisis del líquido sinovial (LS) es una herramienta importante en el diagnóstico de pacientes con artritis idiopática juvenil (AIJ). Pacientes y métodos: Análisis retrospectivo de las características citológicas del LS obtenido de pacientes con AIJ en el periodo 2008-2016. Resultados: Se analizaron 102 LS de 59 pacientes. El 66% fueron mujeres y la forma clínica más frecuente fue la AIJ oligoarticular persistente (52,5%). La mediana de edad al inicio fue de 5 años (RIC 2,4-11,8). El LS generalmente era de características inflamatorias (mediana leucocitos 11.757/mm3; RIC 4.543-18.800) con predominio de polimorfonucleares (PMN, 61%; RIC 30-75). Ocho pacientes (14%) presentaron recuentos inferiores a 2.000 cél/mm3, con predominio de mononucleares (80%), mientras que 3 pacientes (5%) presentaron recuentos superiores a 50.000cél/mm3, con predominio de PMN (90%). No se encontraron diferencias en los recuentos celulares entre las distintas formas de AIJ. La mediana del recuento de leucocitos de pacientes positivos para ANA fue un 20% inferior a la de niños negativos para ANA (9.340 vs. 11.600/mm3; p = 0,23). La proporción de PMN en LS tendía a aumentar conforme se incrementaba la VSG (p < 0,001) y/o la PCR (p = 0,03). No existe correlación del índice JADAS-10 con el recuento en LS (p = 0,4). El LS en artrocentesis simultáneas de diferentes articulaciones mostró una correlación significativa (p = 0,001). Conclusiones: El LS de pacientes con AIJ generalmente tiene características inflamatorias, aunque un 19% presentó recuentos inferiores a 2.000 o superiores a 50.000cél/mm3. Los recuentos en pacientes positivos para ANA tendían a ser menores que en los negativos para ANA (no significativo). La proporción de PMN aumentaba con los reactantes

Introduction: Synovial fluid (SF) analysis is an important tool for the diagnosis of patients with juvenile idiopathic arthritis (JIA). Patients and methods: A retrospective analysis was carried out of cytological features of SF samples obtained from patients with JIA during the period 2008-2016. Results: A total of 102 SF samples from 59 patients were analysed. JIA was more common in females (66%). The most frequent form was persistent oligoarticular JIA (52.5%). The median age at onset was 5 years (IQR 2.4-11.8). SF usually showed an inflammatory pattern (median white blood cells count 11,757/ mm3; IQR 4,543-18,800), with a predominance of polymorphonuclear (PMN) cells (61%; IQR 30-75). Eight patients (14%) had white blood cells counts of less than 2,000 cells/mm3, with predominance of mononuclear cells (80%), whereas 3 patients (5%) had white blood cells counts higher than 50,000 cells/mm3, with a predominance of PMN cells (90%). Synovial white blood cells count did not show significant differences among the different forms of JIA. The median synovial white blood cells count in ANA-positive patients was 20% lower than in ANA-negative (9,340 vs. 11,600/mm3; P = .23). The proportion of PMN increased with increasing levels of ESR (P < .001) and/or CRP (P = .03). No significant correlation was found between JADAS-10 and synovial white blood cells count (P = .4). SF obtained from different joints in simultaneous arthrocentesis showed a significant correlation P = .001). Conclusion: SF from JIA patients usually had inflammatory characteristics, although 19% of the patients showed white blood cells counts below 2,000cells/mm3 or higher than 50,000 cells/mm3. SF cell count was non-significantly lower in ANA-positive patients, and the proportion of PMN increased with increasing levels of ESR/CRP

[Characteristics of synovial fluid in patients with juvenile idiopathic arthritis]. / Características del líquido sinovial en pacientes con artritis idiopática juvenil.

INTRODUCTION: Synovial fluid (SF) analysis is an important tool for the diagnosis of patients with juvenile idiopathic arthritis (JIA). PATIENTS AND METHODS: A retrospective analysis was carried out of cytological features of SF samples obtained from patients with JIA during the period 2008-2016. RESULTS: A total of 102 SF samples from 59 patients were analysed. JIA was more common in females (66%). The most frequent form was persistent oligoarticular JIA (52.5%). The median age at onset was 5 years (IQR 2.4-11.8). SF usually showed an inflammatory pattern (median white blood cells count 11,757/mm3; IQR 4,543-18,800), with a predominance of polymorphonuclear (PMN) cells (61%; IQR 30-75). Eight patients (14%) had white blood cells counts of less than 2,000 cells/mm3, with predominance of mononuclear cells (80%), whereas 3 patients (5%) had white blood cells counts higher than 50,000 cells/mm3, with a predominance of PMN cells (90%). Synovial white blood cells count did not show significant differences among the different forms of JIA. The median synovial white blood cells count in ANA-positive patients was 20% lower than in ANA-negative (9,340 vs. 11,600/mm3; P=.23). The proportion of PMN increased with increasing levels of ESR (P<.001) and/or CRP (P=.03). No significant correlation was found between JADAS-10 and synovial white blood cells count (P=.4). SF obtained from different joints in simultaneous arthrocentesis showed a significant correlation P=.001). CONCLUSION: SF from JIA patients usually had inflammatory characteristics, although 19% of the patients showed white blood cells counts below 2,000cells/mm3 or higher than 50,000cells/mm3. SF cell count was non-significantly lower in ANA-positive patients, and the proportion of PMN increased with increasing levels of ESR/CRP.

Risk of coronary artery involvement in Kawasaki disease.

INTRODUCTION: Kawasaki disease refers to systemic vasculitis with risk of coronary artery disease. Our objective is to identify risk factors associated with coronary artery disease in patients with complete and incomplete Kawasaki disease. MATERIAL AND METHODS: Descriptive, retrospective study conducted in patients diagnosed with Kawasaki disease in a tertiary-care hospital between 2008 and 2014. The American Heart Association diagnostic criteria were used to define complete and incomplete Kawasaki disease. RESULTS: Thirty-one children were diagnosed with Kawasaki disease; 24 met the criteria for the complete form, and 7, for the incomplete form of this condition. Five had coronary artery disease. One of them had incomplete Kawasaki disease (1/7= 14.3%), and the remaining four had the complete form (4/24= 16.7%). No significant differences were found between both groups (p= 1.0). Patients with coronary artery involvement had a higher C-reactive protein level (median: 16.2 mg/dL versus 8.4 mg/dL, p= 0.047) and lower albuminemia (median: 3.2 mg/dL versus 3.99 mg/dL, p= 0.002). CONCLUSIONS: The risk of coronary artery involvement in incomplete Kawasaki disease is similar to that in complete Kawasaki disease; therefore, in patients with the incomplete form, immunoglobulin therapy should not be delayed. In our population, C-reactive protein and albumin levels were related to a higher risk of coronary artery involvement.

INTRODUCCIÓN: La enfermedad de Kawasaki es una vasculitis sistémica con riesgo de afectación coronaria. Nuestro objetivo es identificar los factores de riesgo asociados a la afectación coronaria en pacientes con enfermedad de Kawasaki completa e incompleta. MATERIAL AND MÉTODOS: Estudio descriptivo retrospectivo de los pacientes diagnosticados con enfermedad de Kawasaki en un hospital terciario entre 2008 y 2014. Se utilizaron los criterios diagnósticos de la Asociación Americana de Cardiología para definir la enfermedad de Kawasaki en su forma completa e incompleta. RESULTADOS: Treinta y un niños fueron diagnosticados con enfermedad de Kawasaki; 24 cumplían criterios para la forma completa y 7, para la incompleta. Cinco presentaron afectación coronaria. Uno de ellos presentaba enfermedad de Kawasaki incompleta (1/7= 14,3%), y los 4 restantes, enfermedad de Kawasaki completa (4/24= 16,7%). No se encontraron diferencias significativas en el riesgo de afectación coronaria entre ambos grupos (p= 1,0). Los pacientes con afectación coronaria tenían una proteína C reactiva mayor (mediana: 16,2 mg/dl vs. 8,4 mg/dl; p= 0,047) y una menor albuminemia (mediana: 3,2 mg/dl vs. 3,99 mg/dl; p= 0,002). CONCLUSIONES: El riesgo de afectación coronaria de la enfermedad de Kawasaki incompleta es similar al de la enfermedad de Kawasaki complet por lo que, en pacientes con la forma incompleta de la enfermedad, no se debería demorar el tratamiento con inmunoglobulina. En nuestra población, los valores de proteína C reactiva y de albúmina se relacionan con un mayor riesgo de afectación coronaria.

Riesgo de afectación coronaria en la enfermedad de Kawasaki / Risk of coronary artery involvement in Kawasaki disease

Introducción: La enfermedad de Kawasaki es una vasculitis sistémica con riesgo de afectación coronaria. Nuestro objetivo es identificar los factores de riesgo asociados a la afectación coronaria en pacientes con enfermedad de Kawasaki completa e incompleta. Material y métodos: Estudio descriptivo retrospectivo de los pacientes diagnosticados con enfermedad de Kawasaki en un hospital terciario entre 2008 y 2014. Se utilizaron los criterios diagnósticos de la Asociación Americana de Cardiología para definir la enfermedad de Kawasaki en su forma completa e incompleta. Resultados: Treinta y un niños fueron diagnosticados con enfermedad de Kawasaki; 24 cumplían criterios para la forma completa y 7, para la incompleta. Cinco presentaron afectación coronaria. Uno de ellos presentaba enfermedad de Kawasaki incompleta (1/7= 14,3%), y los 4 restantes, enfermedad de Kawasaki completa (4/24= 16,7%). No se encontraron diferencias significativas en el riesgo de afectación coronaria entre ambos grupos (p= 1,0). Los pacientes con afectación coronaria tenían una proteína C reactiva mayor (mediana: 16,2 mg/dl vs. 8,4 mg/dl; p= 0,047) y una menor albuminemia (mediana: 3,2 mg/dl vs. 3,99 mg/dl; p= 0,002). Conclusiones: El riesgo de afectación coronaria de la enfermedad de Kawasaki incompleta es similar al de la enfermedad de Kawasaki completa, por lo que, en pacientes con la forma incompleta de la enfermedad, no se debería demorar el tratamiento con inmunoglobulina. En nuestra población, los valores de proteína C reactiva y de albúmina se relacionan con un mayor riesgo de afectación coronaria.

Introduction: Kawasaki disease refers to systemic vasculitis with risk of coronary artery disease. Our objective is to identify risk factors associated with coronary artery disease in patients with complete and incomplete Kawasaki disease. Material and methods: Descriptive, retrospective study conducted in patients diagnosed with Kawasaki disease in a tertiary-care hospital between 2008 and 2014. The American Heart Association diagnostic criteria were used to define complete and incomplete Kawasaki disease. Results: Thirty-one children were diagnosed with Kawasaki disease; 24 met the criteria for the complete form, and 7, for the incomplete form of this condition. Five had coronary artery disease. One of them had incomplete Kawasaki disease (1/7= 14.3%), and the remaining four had the complete form (4/24= 16.7%). No significant differences were found between both groups (p= 1.0). Patients with coronary artery involvement had a higher C-reactive protein level (median: 16.2 mg/dL versus 8.4 mg/dL, p= 0.047) and lower albuminemia (median: 3.2 mg/dL versus 3.99 mg/dL, p= 0.002). Conclusions: The risk of coronary artery involvement in incomplete Kawasaki disease is similar to that in complete Kawasaki disease; therefore, in patients with the incomplete form, immunoglobulin therapy should not be delayed. In our population, C-reactive protein and albumin levels were related to a higher risk of coronary artery involvement.

Does the type of event influence how user interactions evolve on Twitter?

The number of people using on-line social networks as a new way of communication is continually increasing. The messages that a user writes in these networks and his/her interactions with other users leave a digital trace that is recorded. Thanks to this fact and the use of network theory, the analysis of messages, user interactions, and the complex structures that emerge is greatly facilitated. In addition, information generated in on-line social networks is labeled temporarily, which makes it possible to go a step further analyzing the dynamics of the interaction patterns. In this article, we present an analysis of the evolution of user interactions that take place in television, socio-political, conference, and keynote events on Twitter. Interactions have been modeled as networks that are annotated with the time markers. We study changes in the structural properties at both the network level and the node level. As a result of this analysis, we have detected patterns of network evolution and common structural features as well as differences among the events.