Dysfunctional phenotype of systemic and pulmonary regulatory T cells associate with lethal COVID-19 cases.

Severe cases of COVID-19 present hyperinflammatory condition that can be fatal. Little is known about the role of regulatory responses in SARS-CoV-2 infection. In this study, we evaluated the phenotype of regulatory T cells in the blood (peripheral blood mononuclear cell) and the lungs (broncho-alveolar) of adult patients with severe COVID-19 under invasive mechanical ventilation. Our results show important dynamic variation on Treg cells phenotype during COVID-19 with changes in number and functional parameters from the day of intubation (Day 1 of intensive care unit admission) to Day 7. We observed that compared with surviving patients, non-survivors presented lower numbers of Treg cells in the blood. In addition, lung Tregs of non-survivors also displayed higher PD1 and lower FOXP3 expressions suggesting dysfunctional phenotype. Further signs of Treg dysregulation were observed in non-survivors such as limited production of IL-10 in the lungs and higher production of IL-17A in the blood and in the lungs, which were associated with increased PD1 expression. These findings were also associated with lower pulmonary levels of Treg-stimulating factors like TNF and IL-2. Tregs in the blood and lungs are profoundly dysfunctional in non-surviving COVID-19 patients.

Frequency of germline genetic variants in women with a personal or family history of breast cancer from Brazil.

BACKGROUND: About 5-10% of breast cancer cases are related to genetic and hereditary factors. The application of Next Generation Sequencing (NGS) in oncology has allowed the identification of genetic variants present in several genes related to the increased risk of breast cancer. This study aimed to determine the frequency of germline genetic variants in patients with a family and/or personal history of breast cancer. METHODS: An analysis of positive reports from NGS panels was carried out in female individuals with a personal and/or family history of breast cancer, present in the database of a private laboratory in Brazil. RESULTS: From about 2000 reports, 183 individuals presented 219 different germline genetic variants. The genes with the highest number of variants were BRCA2 (16.0%), ATM (15.0%) and BRCA1 (12.8%). Among the variants found, 78 were either pathogenic or probably pathogenic, accounting for 35% of all variants discovered. The gene with the highest proportion of pathogenic/probably pathogenic variants was TP53 (80%) and the most frequent pathogenic variant was also reported in this gene (c.1010G > A p.(Arg337His)). Furthermore, the study obtained a high proportion of variants of uncertain significance (VUS) (65%) and approximately 32% of the variants found were in genes of moderate penetrance. CONCLUSIONS: Our results could improve the risk estimation and clinical follow-up of Brazilian patients with a history of breast cancer.

Soluble isoforms of the DC-SIGN receptor can increase the dengue virus infection in immature dendritic cells.

Dengue is a disease with a high-impact on public health worldwide. Many researches have focused on the cell receptors involved in its pathogenesis. The role of soluble isoforms of DC-SIGN (Dendritic Cell-Specific ICAM-3 Grabbing Non-integrin) receptor in the process of Dengue Virus (DENV) infection is not well understood. This work proposes to evaluate changes in the infection process of Immature Dendritic Cells (iDCs) by DENV in the presence of DC-SIGN recombinant soluble isoforms 8, 10, and 12. The recombinant isoforms were built by heterologous expression, the DENV-2 was multiplied in the Aedes albopictus C6/36 cells and quantified in BHK-21 cells, and the iDCs were produced from the THP-1 strain. Infection assays were performed in the presence of iDCs, DENV-2, and isoforms 8, 10, and 12 separately at 25, 50 and 100 ng/mL. The final viral load was estimated by qPCR and statistical analysis was performed by Kruskal-Wallis and ANOVA tests. The iDC profile was confirmed by increasing expression of CD11c, CD86, and CD209 surface markers and maintaining CD14 expression. Infection assays demonstrated a 23-fold increase in DENV viral load in the presence of isoforms 8 and 10 at 100 ng/mL compared to the viral control (p < 0.05), while isoform 12 did not alter the viral load. It was possible to conclude that at 100 ng/mL isoforms (8 and 10) can interact with DENV, increasing viral infection, and potentially acting as opsonins.

Compartmentalized Regulation of Pulmonary and Systemic Inflammation in Critical COVID-19 Patients.

Critical COVID-19 has been associated with altered patterns of cytokines. Distinct inflammatory processes in systemic and pulmonary sites have been reported, but studies comparing these two sites are still scarce. We aimed to evaluate the profile of pulmonary and systemic cytokines and chemokines in critically ill COVID-19 patients. Levels of cytokines and chemokines were measured in plasma samples and minibronchoalveolar lavage of critical COVID-19 patients within 48 h and 5-8 days after intubation. Distinct inflammatory processes were observed in the lungs and blood, which were regulated separately. Survivor patients showed higher lung cytokine levels including IFN-γ, IL-2, IL-4, G-CSF, and CCL4, while nonsurvivors displayed higher levels in the blood, which included IL-6, CXCL8, CXCL10, CCL2, and CCL4. Furthermore, our findings indicate that high TNF and CXCL8 levels in the mini-BAL were associated with better lung oxygen exchange capacity, whereas high levels of IFN-γ in plasma were associated with worse lung function, as measured using the PaO2/FiO2 ratio. These results suggest that a robust and localized inflammatory response in the lungs is protective and associated with survival, whereas a systemic inflammatory response is detrimental and associated with mortality in critical COVID-19.

Biomarkers in Hypertension and Hypertension-related Disorders.

Systemic arterial hypertension (SAH) is a major risk factor for several secondary diseases, especially cardiovascular and renal conditions. SAH has a high prevalence worldwide, and its precise and early recognition is important to prevent the development of secondary outcomes. In this field, the study of biomarkers represents an important approach to diagnosing and predicting the disease and its associated conditions. The use of biomarkers in hypertension and hypertension-related disorders, such as ischemic stroke, intracerebral hemorrhage, transient ischemic attack, acute myocardial infarction, angina pectoris and chronic kidney disease, are discussed in this review. Establishing a potential pool of biomarkers may contribute to a non-invasive and improved approach for their diagnosis, prognosis, risk assessment, therapy management and pharmacological responses to a therapeutic intervention to improve patients' quality of life and prevent unfavorable outcomes.

Frequency of metabolic syndrome in children and adolescents from public schools of Divinópolis, Minas Gerais, Brazil, according to three international diagnostic criteria / Frequência de síndrome metabólica em crianças e adolescentes de escolas públicas de Divinópolis, Minas Gerais, Brasil, conforme três critérios diagnósticos internacionais

AIMS: To assess the frequency of metabolic syndrome in children and adolescents according to three international diagnostic criteria determining the level of agreement between these different criteria. METHODS: Waist circumference, blood pressure, blood glucose, high-density lipoprotein cholesterol, and serum triglycerides were evaluated in students from public schools of different regions of Divinópolis, MG, Brazil. Children and adolescents aged between 10 and 17 years were selected. Criteria adapted from the World Health Organization (WHO), National Cholesterol Education Program ­ Adult Treatment Panel III (NCEP/ATPIII), and International Diabetes Federation (IDF) were used for the diagnosis of metabolic syndrome. The kappa coefficient was used to evaluate the level of agreement among the three criteria. RESULTS: The study evaluated 202 students (86 boys and 116 girls). The frequency of metabolic syndrome was 1.16% for boys and none of the girls presented with metabolic syndrome, according to WHO criteria. According to the NCEP/ATPIII and IDF criteria, metabolic syndrome was not detected in the studied sample. Low blood levels of high-density lipoprotein cholesterol was the most frequent metabolic alteration in all teenagers according to the NCEP/ATPIII and IDF criteria, while body mass index was the most frequent one according to WHO criteria. The level of agreement for one altered parameter was poor when comparing WHO and NCEP/ATP/III, moderate when comparing WHO and IDF and high when comparing the NCEP/ATP/III and IDF criteria. CONCLUSIONS: Significant differences between the frequencies of individual metabolic syndrome parameters were found in the studied sample of children and adolescents, depending on the criteria used. According to WHO criteria, metabolic syndrome was found at a low frequency and only in boys, while the NCEP/ATPIII and IDF criteria did not diagnose metabolic syndrome. The present findings suggest the need to reach a consensus on the cut-off points for risk factors and a single diagnostic definition of metabolic syndrome in children and adolescents.