Integrative systems immunology uncovers molecular networks of the cell cycle that stratify COVID-19 severity.

Several perturbations in the number of peripheral blood leukocytes, such as neutrophilia and lymphopenia associated with Coronavirus disease 2019 (COVID-19) severity, point to systemic molecular cell cycle alterations during severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection. However, the landscape of cell cycle alterations in COVID-19 remains primarily unexplored. Here, we performed an integrative systems immunology analysis of publicly available proteome and transcriptome data to characterize global changes in the cell cycle signature of COVID-19 patients. We found significantly enriched cell cycle-associated gene co-expression modules and an interconnected network of cell cycle-associated differentially expressed proteins (DEPs) and genes (DEGs) by integrating the molecular data of 1469 individuals (981 SARS-CoV-2 infected patients and 488 controls [either healthy controls or individuals with other respiratory illnesses]). Among these DEPs and DEGs are several cyclins, cell division cycles, cyclin-dependent kinases, and mini-chromosome maintenance proteins. COVID-19 patients partially shared the expression pattern of some cell cycle-associated genes with other respiratory illnesses but exhibited some specific differential features. Notably, the cell cycle signature predominated in the patients' blood leukocytes (B, T, and natural killer cells) and was associated with COVID-19 severity and disease trajectories. These results provide a unique global understanding of distinct alterations in cell cycle-associated molecules in COVID-19 patients, suggesting new putative pathways for therapeutic intervention.

Selenium biomarkers and miR-7-5p in overweight/obese women.

INTRODUCTION: Chronic low-grade inflammation and oxidative stress are pivotal contributors to the metabolic complications associated with obesity. Selenoprotein P (SELENOP) and glutathione peroxidase 1 (GPx1) are selenoproteins involved in the reduction of reactive oxygen species and pro-inflammatory cytokines levels. Nutritional epigenomics revealed the interaction of microRNAs and nutrients with an important impact on metabolic pathways involved in obesity. However, the knowledge regarding the influence of microRNA on selenium biomarkers and its impact on metabolic pathways related to obesity remains scarce. Thus, the aim of this study was to investigate the association of plasma miR-7-5p expression with selenium and inflammatory biomarkers in women with overweight/obesity. MATERIAL AND METHODS: Anthropometric evaluations were performed and blood samples were collected for the analysis of fasting glucose, insulin, inflammatory and selenium biomarkers, and miR-7-5p expression in 54 women with overweight/obesity. Gene expression of SELENOP and GPX1 were evaluated in peripheral mononuclear blood cells. RESULTS: This study observed a negative correlation between SELENOP levels and miR-7-5p (rho = -0.350; p = 0.018). Additionally, it was observed that body fat (OR = 0.737; p = 0.011), age (OR = 1.214; p = 0.007), and miR-7-5p (OR = 0.990; p = 0.015) emerged as significant predictors of SELENOP levels. CONCLUSIONS: In conclusion, we observed a significant inverse association between miR-7-5p expression and SELENOP concentration in overweight/obese women, suggesting that age and percentage of body fat are also associated. TRIAL REGISTRATION NUMBER: Brazilian Registry of Clinical Trials (ReBEC) number RBR-2nfy5q.

The let-7b-5p, miR-326, and miR-125a-3p are associated with left ventricular systolic dysfunction in post-myocardial infarction.

Background: Acute ST-elevation myocardial infarction (STEMI) can lead to adverse cardiac remodeling, resulting in left ventricular systolic dysfunction (LVSd) and heart failure. Epigenetic regulators, such as microRNAs, may be involved in the physiopathology of LVSd. Objective: This study explored microRNAs in peripheral blood mononuclear cells (PBMC) of post-myocardial infarction patients with LVSd. Methods: Post-STEMI patients were grouped as having (LVSd, n = 9) or not LVSd (non-LVSd, n = 16). The expression of 61 microRNAs was analyzed in PBMC by RT-qPCR and the differentially expressed microRNAs were identified. Principal Component Analysis stratified the microRNAs based on the development of dysfunction. Predictive variables of LVSd were investigated through logistic regression analysis. A system biology approach was used to explore the regulatory molecular network of the disease and an enrichment analysis was performed. Results: The let-7b-5p (AUC: 0.807; 95% CI: 0.63-0.98; p = 0.013), miR-125a-3p (AUC: 0.800; 95% CI: 0.61-0.99; p = 0.036) and miR-326 (AUC: 0.783; 95% CI: 0.54-1.00; p = 0.028) were upregulated in LVSd (p < 0.05) and discriminated LVSd from non-LVSd. Multivariate logistic regression analysis showed let-7b-5p (OR: 16.00; 95% CI: 1.54-166.05; p = 0.020) and miR-326 (OR: 28.00; 95% CI: 2.42-323.70; p = 0.008) as predictors of LVSd. The enrichment analysis revealed association of the targets of these three microRNAs with immunological response, cell-cell adhesion, and cardiac changes. Conclusion: LVSd alters the expression of let-7b-5p, miR-326, and miR-125a-3p in PBMC from post-STEMI, indicating their potential involvement in the cardiac dysfunction physiopathology and highlighting these miRNAs as possible LVSd biomarkers.

Biomarkers of Zinc and Copper Status and Associated Factors in Outpatients with Ischemic and Non-Ischemic Heart Failure.

Background: Few studies have explored the impact of ischemic and non-ischemic etiologies of heart failure and other factors associated with heart failure on zinc and copper status. This study examined zinc and copper status in 80 outpatients with ischemic (n = 36) and non-ischemic (n = 44) heart failure and associations with biodemographic, clinical, biochemical, and nutritional parameters.Materials: Biomarkers of plasma zinc and copper, copper-zinc ratio, 24-h urinary zinc excretion, ceruloplasmin, and dietary intake of zinc and copper were assessed. Plasma zinc and copper and urinary zinc were measured by inductively coupled plasma mass spectrometry (ICP-MS).Results: Patients with ischemic heart failure showed lower dietary zinc intake and higher dietary copper intake (both p = 0.02). Zinc and copper in plasma, copper-zinc ratio, ceruloplasmin, and 24-h urinary zinc excretion showed no statistical differences between the groups (all p ≥ 0.05). An inverse association was found between age (ß =-0.001; p = 0.005) and the use of diuretics (ß = -0.047; p = 0.013) and plasma zinc. Copper levels in plasma (ß = 0.001; p < 0.001), and albumin (ß = 0.090; p<0.001) were directly associated with plasma zinc. A positive association was found between ceruloplasmin (ß = 0.011; p < 0.001), gamma-glutamyl transferase (ß = 0.001; p < 0.001), albumin (ß = 0.077; p = 0.001), and high-sensitivity c-reactive protein (ß = 0.001; p = 0.024) and plasma copper.Conclusion: Zinc and copper biomarkers in clinically stable patients with heart failure did not seem to be responsive to the differences in zinc and copper intake observed in this study, regardless of heart failure etiology. The predictors of plasma zinc and copper levels related to oxidative stress and inflammation should be monitored in heart failure clinical practice.

Lack of Association between Inadequate Micronutrient Intake and Prognosis in Outpatients with Heart Failure.

Inadequate nutrient intake can lead to worse outcomes in patients with heart failure (HF). This prospective cohort study aimed to assess the prevalence of inadequate micronutrient intake and their association with prognosis in 121 adult and elderly outpatients with HF. Habitual micronutrient intake was evaluated using 24-h dietary recalls (minimum 2 and maximum 6). Participants were grouped into moderate (n = 67) and high (n = 54) micronutrient deficiency groups, according to the individual assessment of each micronutrient intake. Patients' sociodemographic, clinical, and anthropometric data and clinical outcomes (hospitalization and mortality) within 24 months were collected. Overall and event-free survival rates were calculated using Kaplan-Meier estimates, and curves were compared using the log-rank test. The death risk rate (hazard ratio (HR)) was calculated using Cox's univariate model. The rate of inadequate intake was 100% for vitamins B1 and D and above 80% for vitamins B2, B9, and E, calcium, magnesium, and copper. No differences in overall survival and event-free survival were observed between groups of HF outpatients with moderate and high micronutrient deficiencies (HR = 0.94 (CI = 0.36-2.48), p = 0.91, and HR = 1.63 (CI = 0.68-3.92), p = 0.26, respectively), as well as when the inadequacy of each micronutrient intake was evaluated alone (all p > 0.05). In conclusion, a high prevalence of inadequate micronutrient intake was observed in outpatients with HF. Inadequate micronutrient intake was not associated with hospitalization and mortality in this group of patients.

Previous vitamin D status and total cholesterol are associated with SARS-CoV-2 infection.

BACKGROUND: The relationship of vitamin D status and other biochemical parameters with the risk of SARS-CoV-2 infection remains inconclusive, especially in regions with high solar incidence. Therefore, we aimed to associate the 25-hydroxyvitamin D (25(OH)D) concentrations and lipid profile prior to the SARS-CoV-2 tests in a population from a sunny region in Brazil (5 degrees S, 35 degrees W). METHODS: This retrospective cohort study enrolled 1634 patients tested for SARS-CoV-2 of a private medical laboratory with 25(OH)D concentration and lipid profile measured ≥ 7 days before the date of the first SARS-CoV-2 RT-PCR test and were categorized according to 25(OH)D sufficiency (≥30 ng/mL) or insufficiency (<30 ng/mL). Multiple logistic regression analyses were performed to assess risk factors associated with positive tests for SARS-CoV-2. RESULTS: Average serum 25(OH)D was 33.6 ng/mL. Vitamin D deficiency (<20 ng/mL) was only found in 2.6% of the participants. Multivariate analysis demonstrated that patients > 49 y with insufficient 25(OH)D (<30 ng/mL) presented increased odds to test positive for SARS-CoV-2 (OR: 2.02, 95 %CI: 1.15 to 3.55, P = 0.015). The same is observed among those with total cholesterol > 190 mg/dL (OR: 1.90, 95 %CI: 1.10 to 3.28, P = 0.020). CONCLUSIONS: Previous insufficient 25(OH)D (<30 ng/mL) concentration and high total cholesterol were associated with SARS-CoV-2 infection among adults > 48 y in the study population. Further studies should be conducted to confirm whether measurement of 25(OH)D and lipid profile could be useful to identify patients who are more susceptible to COVID-19.

Vitamin D status and predictors of 25-hydroxyvitamin D levels in patients with heart failure living in a sunny region.

INTRODUCTION: Aims: hypovitaminosis D has frequently been identified in patients with heart failure (HF). However, few studies have been conducted in regions with high solar incidence. Therefore, this study aimed to evaluate vitamin D status and predictors of 25-hydroxyvitamin D (25(OH)D) levels in patients with HF living in a sunny region (5 °- 6 °S). Methods: this cross-sectional study enrolled 70 patients with HF. Biodemographic, clinical, biochemical, dietary, and sun exposure data were collected, and 25(OH)D levels were measured. Results: the mean 25(OH)D level was 40.1 (12.4) ng/mL, and 24.3 % (95 % CI: 14.2-33.8) of patients with HF had hypovitaminosis D (25(OH)D < 30 ng/mL). Female patients (p = 0.001), those with ischemic etiology (p = 0.03) and those with high parathyroid hormone levels (> 67 pg/mL) (p = 0.034) were more likely to present hypovitaminosis D. Higher 25(OH)D levels were observed in men than in women (ß = 7.78, p = 0.005) and in patients with HF in New York Heart Association (NHYA) functional class I when compared to those in class III/IV (ß = 8.23, p = 0.032). Conclusions: the majority of patients with HF had sufficient 25(OH)D levels. Sex and functional classification were identified as independent predictors of 25(OH)D levels. These results highlight the need for increased monitoring of vitamin D status among female patients with heart failure and those with more severe symptoms.

INTRODUCCIÓN: Objetivos: la hipovitaminosis D se ha identificado con frecuencia en pacientes con insuficiencia cardíaca (IC). Sin embargo, pocos estudios se han realizado en regiones con una alta exposición solar. Por lo tanto, este estudio tuvo como objetivo evaluar el estado de la vitamina D y los predictores de los niveles de 25-hidroxivitamina D (25(OH)D) en pacientes con IC que viven en una región soleada (5 °-6 °S). Métodos: este estudio transversal incluyó a 70 pacientes con IC. Se recopilaron datos biodemográficos, clínicos, bioquímicos, dietéticos y de exposición solar, y se midieron los niveles de 25(OH)D. Resultados: el nivel medio de 25(OH)D fue de 40,1 (12,4) ng/mL y el 24,3 % (IC 95 %: 14,2-33,8) de los pacientes con IC tenían hipovitaminosis D (25(OH)D < 30 ng/mL. Las pacientes mujeres (p = 0,001), aquellos con IC de etiología isquémica (p = 0,03) y aquellos otros pacientes con niveles altos de hormona paratiroidea (> 67 pg/mL) (p = 0,034) tenían más probabilidades de presentar hipovitaminosis D. Se observaron niveles más altos de 25(OH)D en los hombres que en las mujeres (ß = 7,78, p = 0,005), y en los pacientes con IC de clase funcional I de la New York Heart Association (NHYA) que en los de clase III/IV (ß = 8,23, p = 0,032). Conclusiones: la mayoría de los pacientes con IC tenían niveles suficientes de 25(OH)D. El sexo y la clasificación funcional se identificaron como predictores independientes de los niveles de 25(OH)D. Estos resultados destacan la necesidad de un mayor control del estado de la vitamina D entre las mujeres con insuficiencia cardíaca y los pacientes con síntomas más graves.