The Quality of SARS-CoV-2-Specific T Cell Functions Differs in Patients with Mild/Moderate versus Severe Disease, and T Cells Expressing Coinhibitory Receptors Are Highly Activated.

Understanding the function of SARS-CoV-2 Ag-specific T cells is crucial for the monitoring of antiviral immunity and vaccine design. Currently, both impaired and robust T cell immunity is described in COVID-19 patients. In this study, we explored and compared the effector functions of SARS-CoV-2-reactive T cells expressing coinhibitory receptors and examine the immunogenicity of SARS-CoV-2 S, M, and N peptide pools in regard to specific effector T cell responses, Th1/Th2/Th17, in COVID-19 patients. Analyzing a cohort of 108 COVID-19 patients with mild, moderate, and severe disease, we observed that coinhibitory receptors (e.g., PD-1, CTLA-4, TIM-3, VISTA, CD39, CD160, 2B4, TIGIT, Gal-9, and NKG2A) were upregulated on both CD4+ and CD8+ T cells. Importantly, the expression of coinhibitory receptors on T cells recognizing SARS-CoV-2 peptide pools (M/N/S) was associated with increased frequencies of cytokine-producing T cells. Thus, our data refute the concept of pathological T cell exhaustion in COVID-19 patients. Despite interindividual variations in the T cell response to viral peptide pools, a Th2 phenotype was associated with asymptomatic and milder disease, whereas a robust Th17 was associated with severe disease, which may potentiate the hyperinflammatory response in patients admitted to the Intensive Care Unit. Our data demonstrate that T cells may either play a protective or detrimental role in COVID-19 patients. This finding could have important implications for immune correlates of protection, diagnostic, and prophylaxis with respect to COVID-19 management.

Differential Signature of the Microbiome and Neutrophils in the Oral Cavity of HIV-Infected Individuals.

HIV infection is associated with a wide range of changes in microbial communities and immune cell components of the oral cavity. The purpose of this study was to evaluate the oral microbiome in relationship to oral neutrophils in HIV-infected compared to healthy individuals. We evaluated oral washes and saliva samples from HIV-infected individuals (n=52) and healthy controls (n=43). Using 16S-rRNA gene sequencing, we found differential ß-diversity using Principal Coordinate Analysis (PCoA) with Bray-Curtis distances. The α-diversity analysis by Faith's, Shannon, and observed OTUs indexes indicated that the saliva samples from HIV-infected individuals harbored significantly richer bacterial communities compared to the saliva samples from healthy individuals. Notably, we observed that five species of Spirochaeta including Spirochaetaceae, Spirochaeta, Treponema, Treponema amylovorum, and Treponema azotonutricum were significantly abundant. In contrast, Helicobacter species were significantly reduced in the saliva of HIV-infected individuals. Moreover, we found a significant reduction in the frequency of oral neutrophils in the oral cavity of HIV-infected individuals, which was positively related to their CD4+ T cell count. In particular, we noted a significant decline in CD44 expressing neutrophils and the intensity of CD44 expression on oral neutrophils of HIV-infected individuals. This observation was supported by the elevation of soluble CD44 in the saliva of HIV-infected individuals. Overall, the core oral microbiome was distinguishable between HIV-infected individuals on antiretroviral therapy compared to the HIV-negative group. The observed reduction in oral neutrophils might likely be related to the low surface expression of CD44, resulting in a higher bacterial diversity and richness in HIV-infected individuals.

Galectin-9, a Player in Cytokine Release Syndrome and a Surrogate Diagnostic Biomarker in SARS-CoV-2 Infection.

The outbreak of SARS-CoV-2 infection has enormously impacted our lives. Clinical evidence has implicated the emergence of cytokine release syndrome as the prominent cause of mortality in COVID-19 patients. In this study, we observed massive elevation of plasma Galectin-9 (Gal-9) in COVID-19 patients compared to healthy controls (HCs). By using the receiver operating characteristic (ROC) curve, we found that a baseline of 2,042 pg/ml plasma Gal-9 can differentiate SARS-CoV-2-infected from noninfected individuals with high specificity/sensitivity (95%). Analysis of 30 cytokines and chemokines detected a positive correlation of the plasma Gal-9 with C-reactive protein (CRP) and proinflammatory cytokines/chemokines such as interleukin-6 (IL-6), tumor necrosis factor alpha (TNF-α), IP-10, MIP-1α, and MCP-1 but an inverse correlation with transforming growth factor ß (TGF-ß) in COVID-19 patients. In agreement, we found enhanced production of IL-6 and TNF-α by monocytes and NK cells of COVID-19 patients once treated with the recombinant human Gal-9 in vitro Also, we observed that although the cell-membrane expression of Gal-9 on monocytes does not change in COVID-19 patients, those with higher Gal-9 expression exhibit an activated phenotype. Furthermore, we noted significant downregulation of surface Gal-9 in neutrophils from COVID-19 patients compared to HCs. Our further investigations indicated that immune activation following SARS-CoV-2 infection results in Gal-9 shedding from neutrophils. The strong correlation of Gal-9 with proinflammatory mediators suggests that inhibition of Gal-9 may severe as a therapeutic approach in COVID-19 infection. Besides, the plasma Gal-9 measurement may be used as a surrogate diagnostic biomarker in COVID-19 patients.IMPORTANCE The outbreak of SARS-CoV-2 infection has enormously impacted our lives. Clinical evidence has implicated the emergence of cytokine release syndrome as the prominent cause of mortality in COVID-19 patients. We observed substantial elevation of the plasma Galectin-9 (Gal-9) in COVID-19 patients compared to healthy controls. Gal-9 is an abundant protein in many immune and nonimmune cells. We found that Gal-9 detection assay can differentiate SARS-CoV-2-infected from noninfected individuals with a specificity/sensitivity of 95%. Importantly, we found a positive correlation of the plasma Gal-9 with a wide range of proinflammatory biomarkers in COVID-19 patients. In agreement, we found enhanced expression and production of such proinflammatory molecules by immune cells of COVID-19 patients once treated with Gal-9 in vitro Our results propose Gal-9 as an important contributing factor in cytokine release syndrome; therefore, Gal-9 inhibition may serve as a beneficial therapeutic approach by suppressing the hyperimmune activation in COVID-19 patients.

Impacto de la fluorosis dental en la calidad de vida de adolescentes ecuatorianos de entre 11 a 14 años / Impact of dental fluorosis over the quality of life of ecuadorian teenagers between 11 and 14 years

Resumen El propósito de este estudio fue determinar el impacto de la fluorosis dental (FD) en la calidad de vida (CV) de adolescentes entre 11 a 14 años del cantón Latacunga, Cotopaxi, Ecuador. Materiales y métodos: Se plantea un estudio descriptivo, en una muestra de 128 adolescentes entre 11 a 14 años y sus respectivos padres, empleando como instrumentos de recolección de información, la encuesta INEN para determinar el nivel socioeconómico, el cuestionario CPQ11-14 para precisar calidad de vida, y un registro fotográfico intraoral de cada adolescente, analizado posteriormente por tres investigadores según el índice de Thylstrup y Fejerskov (TF). Un análisis químico sobre la concentración de flúor en las fuentes de abastecimiento de agua de consumo, fue ejecutado complementariamente. Resultados: La prevalencia de FD fue de 70,3% en los grados TF 1, 2,3. El análisis químico del agua mostró una media de flúor de 1,06 mg/l. Las pruebas estadísticas revelaron una relación de la CV con FD (p = 0,000) y con el nivel socioeconómico (p = 0,001). Conclusiones: La CV se ve afectada con la presencia de FD y el nivel socioeconómico, sin relación con la edad, sexo o la presencia de flúor en el agua de consumo.

Abstract The purpose of this study was to determine the impact of dental fluorosis (DF) over the quality of life (QoL) of adolescents between 11 and 14 years old, of Latacunga, Cotopaxi, Ecuador. Materials and methods: This descriptive study had a sample of 128 adolescents between 11 to 14 years old and their respective parents. The information was collected through, the INEN survey to determine socioeconomic status and the CPQ11-14 survey to determine adolescents' QoL. In addition, intraoral photographic records were obtained for DF detection according Thylstrup and Fejerskov index (TF) and the public water company accomplished chemical analysis of fluoride concentration in water sources. Results: The prevalence of DF was 70.3% corresponding to TF 1, 2, 3 index. Chemical analyzes of water showed an average of 1.06 mg / l on Fluoride levels. Statistical analysis showed correlation between QoL and Fluorosis presence (p = 0.000) and QoL to socio-economic level (p = 0.001). Conclusions: QoL relates to DF and the socio-economic level. However, it is not to age, sex or fluoride levels in consumption water. Key words: Teenagers, dental fluorosis, oral health, life quality, water fluoridation, epidemiology, dental health survey, public health dentistry.

Calidad de vida y salud bucal en preescolares ecuatorianos relacionadas con el nivel educativo de sus padres / Quality of life and oral health among Ecuadorian preschoolers in relation to the educational level of their parents

Introducción: La caries dental infantil constituye un problema de salud pública en el Ecuador. Los niños de 3 a 5 años que padecen caries dental decidua, sufren complicaciones como dolor al comer y dormir, alteración del estado de ánimo, inasistencia escolar; en general, un impacto negativo en su calidad de vida. Los padres cumplen un rol clave en el cuidado de la salud bucal de sus hijos, el cual es determinado muchas veces por su nivel educativo. Objetivo: Determinar el impacto que la salud bucal tiene en la calidad de vida de preescolares, evaluado por sus padres o responsables y relacionado con su nivel de educación. Métodos: Se realizó un estudio descriptivo y transversal. Se evaluaron a 382 padres y/o representantes de preescolares niños y niñas entre 3 a 5 años pertenecientes a cuatro provincias del Ecuador seleccionadas a conveniencia del investigador; quienes previa aceptación de participación y firma de consentimiento informado respondieron la encuesta ECOHIS (Early Childhood Oral Health Impact Scale) versión en español, que valora la relación entre salud bucal y calidad de vida en preescolares. Los datos recolectados fueron tabulados en tablas de Excel y analizados mediante software libre R.V3.4.1 empleando intervalos de verosimilitud al 14,7 por ciento equivalente al 95 por ciento de confianza para proporciones, y prueba estadística de chi cuadrado. Resultados: Los valores de significancia fueron: al relacionar con el dolor referido por los niños (p=0,152), las dificultades al beber (p= 0,003), consumir alimentos (p= 0,03), al sonreír (p= 0,002), al hablar (p= 0,09) y la repercusión económica asociada a problemas de salud bucal (p= 0,003). Conclusiones: Existe asociación entre el nivel de educación de los padres y su percepción sobre la influencia que tiene la salud bucal en la calidad de vida de sus hijos(AU)

Introduction: Childhood dental caries is a public health problem in Ecuador. Children aged 3-5 years with deciduous dental caries experience unpleasant symptoms such as pain while eating or sleeping, mood changes and school absenteeism, all of which has a negative impact on their quality of life. The key role played by parents in the oral care of their children is often determined by their educational level. Objective: Determine the impact of oral health on the quality of life of preschoolers aged under 5 years as evaluated by their parents or guardians and in relation to their educational level. Methods: A descriptive cross-sectional study was conducted of 382 parents and/or guardians of preschool children aged 3-5 years from four Ecuadorian provinces selected by convenience sampling, who gave their informed consent and answered the ECOHIS (Early Childhood Oral Health Impact Scale) survey, Spanish version, which assesses the relationship between oral health and quality of life among preschoolers. The surveys were identified with codes. The data collected were transferred onto Excel tables and analyzed with the free software R.V3.4.1 using likelihood ratios at 14.7 percent equivalent to 95 percent confidence intervals for proportions, as well as the chi-square statistical test. Results: The following significance levels were obtained: for pain as reported by children (p=0.152), for difficulty when drinking (p= 0.003), eating (p= 0.03), smiling (p= 0.002), speaking (p= 0.09), and for economic impact associated to oral health problems (p= 0.003). Conclusions: An association was found between the educational level of parents and their perception of the influence of oral health upon the quality of life of their children(AU)