Maintained imbalance of triglycerides, apolipoproteins, energy metabolites and cytokines in long-term COVID-19 syndrome patients.

Background: Deep metabolomic, proteomic and immunologic phenotyping of patients suffering from an infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have matched a wide diversity of clinical symptoms with potential biomarkers for coronavirus disease 2019 (COVID-19). Several studies have described the role of small as well as complex molecules such as metabolites, cytokines, chemokines and lipoproteins during infection and in recovered patients. In fact, after an acute SARS-CoV-2 viral infection almost 10-20% of patients experience persistent symptoms post 12 weeks of recovery defined as long-term COVID-19 syndrome (LTCS) or long post-acute COVID-19 syndrome (PACS). Emerging evidence revealed that a dysregulated immune system and persisting inflammation could be one of the key drivers of LTCS. However, how these biomolecules altogether govern pathophysiology is largely underexplored. Thus, a clear understanding of how these parameters within an integrated fashion could predict the disease course would help to stratify LTCS patients from acute COVID-19 or recovered patients. This could even allow to elucidation of a potential mechanistic role of these biomolecules during the disease course. Methods: This study comprised subjects with acute COVID-19 (n=7; longitudinal), LTCS (n=33), Recov (n=12), and no history of positive testing (n=73). 1H-NMR-based metabolomics with IVDr standard operating procedures verified and phenotyped all blood samples by quantifying 38 metabolites and 112 lipoprotein properties. Univariate and multivariate statistics identified NMR-based and cytokine changes. Results: Here, we report on an integrated analysis of serum/plasma by NMR spectroscopy and flow cytometry-based cytokines/chemokines quantification in LTCS patients. We identified that in LTCS patients lactate and pyruvate were significantly different from either healthy controls (HC) or acute COVID-19 patients. Subsequently, correlation analysis in LTCS group only among cytokines and amino acids revealed that histidine and glutamine were uniquely attributed mainly with pro-inflammatory cytokines. Of note, triglycerides and several lipoproteins (apolipoproteins Apo-A1 and A2) in LTCS patients demonstrate COVID-19-like alterations compared with HC. Interestingly, LTCS and acute COVID-19 samples were distinguished mostly by their phenylalanine, 3-hydroxybutyrate (3-HB) and glucose concentrations, illustrating an imbalanced energy metabolism. Most of the cytokines and chemokines were present at low levels in LTCS patients compared with HC except for IL-18 chemokine, which tended to be higher in LTCS patients. Conclusion: The identification of these persisting plasma metabolites, lipoprotein and inflammation alterations will help to better stratify LTCS patients from other diseases and could help to predict ongoing severity of LTCS patients.

High-Density Lipoprotein function is modulated by the SARS-CoV-2 spike protein in a lipid-type dependent manner.

There is a close relationship between the SARS-CoV-2 virus and lipoproteins, in particular high-density lipoprotein (HDL). The severity of the coronavirus disease 2019 (COVID-19) is inversely correlated with HDL plasma levels. It is known that the SARS-CoV-2 spike (S) protein binds the HDL particle, probably depleting it of lipids and altering HDL function. Based on neutron reflectometry (NR) and the ability of HDL to efflux cholesterol from macrophages, we confirm these observations and further identify the preference of the S protein for specific lipids and the consequent effects on HDL function on lipid exchange ability. Moreover, the effect of the S protein on HDL function differs depending on the individuals lipid serum profile. Contrasting trends were observed for individuals presenting low triglycerides/high cholesterol serum levels (LTHC) compared to high triglycerides/high cholesterol (HTHC) or low triglycerides/low cholesterol serum levels (LTLC). Collectively, these results suggest that the S protein interacts with the HDL particle and, depending on the lipid profile of the infected individual, it impairs its function during COVID-19 infection, causing an imbalance in lipid metabolism.

Outcomes of the Indonesian Chronic Disease Management Program (PROLANIS) in Patients with Hypertension During the COVID-19 Pandemic in Rural Areas: A Preliminary Evaluation Study.

BACKGROUND The Indonesian Chronic Disease Management Program (PROLANIS) is a government program that aims to improve the health outcomes of patients with chronic diseases, including hypertension. This preliminary study aimed to evaluate the impacts of the coronavirus disease 2019 (COVID-19) pandemic on the health outcomes of hypertension patients in rural areas who were enrolled in PROLANIS. MATERIAL AND METHODS This study used data from 4 PROLANIS groups in East Java province. The data were collected from participants' 6-month evaluations at 3 time points: before the COVID-19 pandemic in December 2019 (T0), during the COVID-19 pandemic in June 2020 (T1), and in December 2020 (T2). Evaluated parameters were body mass index (BMI), systolic blood pressure (SBP), diastolic blood pressure (DBP), total cholesterol (TC), low-density lipid (LDL), high-density lipid (HDL), triglyceride (TG), and estimated glomerular filtration rate (eGFR). RESULTS There were 91 patients included in the analyses. Compared to T0, BMI, blood pressure, eGFR, and TC had significantly deteriorated at T1, but LDL, HDL, and TG showed no marked changes. At T2, BMI, DBP, and TC were similar to T0. On the other hand, SBP and eGFR did not improve, while HDL significantly deteriorated. Stratified based on age, worsening of DBP, TC, and LDL at T1 and eGFR at T1 and T2 was only observed in those aged 60 years and older. CONCLUSIONS This preliminary study showed that the health outcomes of hypertension patients in rural areas who were enrolled in PROLANIS were negatively impacted during the COVID-19 pandemic, with the elderly being the most affected.

The Effect of a Moderately Restricted Carbohydrate Diet on Cardiometabolic Risk Factors in Overweight and Obese Women With Metabolic Syndrome: A Randomized Controlled Trial.

PURPOSE: Metabolic syndrome (MetS) is a major public health concern that increases the risk of cardiovascular disease and mortality. In previous studies of MetS management, low-carbohydrate diets have been strongly emphasized, despite the fact that many apparently healthy individuals have difficulties adhering to these diets on a long-term basis. The purpose of the present study was to elucidate the effects of a moderately restricted carbohydrate diet (MRCD) on cardiometabolic risk factors in women with MetS. METHODS: This parallel 3-month, single-blind randomized controlled trial was conducted in Tehran, Iran, among 70 women with overweight or obesity aged 20 to 50 years with MetS. Patients were randomly allocated to receive either MRCD (42%-45% carbohydrates and 35%-40% fats) (n = 35) or a normal weight loss diet (NWLD) (52%-55% carbohydrates and 25%-30% fats) (n = 35). Both diets contained the same quantity of protein, which accounted for 15% to 17% of total energy. Anthropometric measurements, blood pressure, lipid profile, and glycemic indices were all assessed before and after the intervention. FINDINGS: Compared with the NWLD group, following an MRCD significantly decreased weight (-4.82 vs -2.40 kg; P = 0.01), body mass index (-1.88 vs -0.94 kg/m2; P = 0.01), waist circumference (-5.34 vs -2.75 cm; P = 0.01), hip circumference (-2.58 vs -1.11 cm; P = 0.01), serum triglyceride (-26.8 vs -7.19 mg/dL; P = 0.01), and increased serum HDL-C levels (1.89 vs. 0.24 mg/dL; P = 0.01). There was no significant difference between the 2 diets in waist-to-hip ratio, serum total cholesterol, serum LDL-C, systolic and diastolic blood pressure, fasting blood glucose, insulin levels, or the homeostasis model assessment for insulin resistance. IMPLICATIONS: Moderate carbohydrate replacement with dietary fats significantly improved weight, body mass index, waist circumference, hip circumference, serum triglyceride, and HDL-C levels among women with MetS. Iranian Registry of Clinical Trials identifier: IRCT20210307050621N1.

Indian food habit & food ingredients may have a role in lowering the severity & high death rate from COVID-19 in Indians: findings from the first nutrigenomic analysis.

Background & objectives: During the COVID-19 pandemic, the death rate was reportedly 5-8 fold lower in India which is densely populated as compared to less populated western countries. The aim of this study was to investigate whether dietary habits were associated with the variations in COVID-19 severity and deaths between western and Indian population at the nutrigenomics level. Methods: In this study nutrigenomics approach was applied. Blood transcriptome of severe COVID-19 patients from three western countries (showing high fatality) and two datasets from Indian patients were used. Gene set enrichment analyses were performed for pathways, metabolites, nutrients, etc., and compared for western and Indian samples to identify the food- and nutrient-related factors, which may be associated with COVID-19 severity. Data on the daily consumption of twelve key food components across four countries were collected and a correlation between nutrigenomics analyses and per capita daily dietary intake was investigated. Results: Distinct dietary habits of Indians were observed, which may be associated with low death rate from COVID-19. Increased consumption of red meat, dairy products and processed foods by western populations may increase the severity and death rate by activating cytokine storm-related pathways, intussusceptive angiogenesis, hypercapnia and enhancing blood glucose levels due to high contents of sphingolipids, palmitic acid and byproducts such as CO2 and lipopolysaccharide (LPS). Palmitic acid also induces ACE2 expression and increases the infection rate. Coffee and alcohol that are highly consumed in western countries may increase the severity and death rates from COVID-19 by deregulating blood iron, zinc and triglyceride levels. The components of Indian diets maintain high iron and zinc concentrations in blood and rich fibre in their foods may prevent CO2 and LPS-mediated COVID-19 severity. Regular consumption of tea by Indians maintains high high-density lipoprotein (HDL) and low triglyceride in blood as catechins in tea act as natural atorvastatin. Importantly, regular consumption of turmeric in daily food by Indians maintains strong immunity and curcumin in turmeric may prevent pathways and mechanisms associated with SARS-CoV-2 infection and COVID-19 severity and lowered the death rate. Interpretation & conclusions: Our results suggest that Indian food components suppress cytokine storm and various other severity related pathways of COVID-19 and may have a role in lowering severity and death rates from COVID-19 in India as compared to western populations. However, large multi-centered case-control studies are required to support our current findings.

Effect of a ketogenic diet versus Mediterranean diet on glycated hemoglobin in individuals with prediabetes and type 2 diabetes mellitus: The interventional Keto-Med randomized crossover trial.

BACKGROUND: Consensus has not been reached on what constitutes an optimal diet in individuals with prediabetes and type 2 diabetes mellitus (T2DM), especially between low-carbohydrate options. OBJECTIVES: We compared 2 low-carbohydrate diets with 3 key similarities (incorporating nonstarchy vegetables and avoiding added sugars and refined grains) and 3 key differences (incorporating compared with avoiding legumes, fruits, and whole, intact grains) for their effects on glucose control and cardiometabolic risk factors in individuals with prediabetes and T2DM. METHODS: Keto-Med was a randomized, crossover, interventional trial. Forty participants aged ≥18 years with prediabetes or T2DM followed the well-formulated ketogenic diet (WFKD) and the Mediterranean-plus diet (Med-Plus) for 12 weeks each, in random order. The diets shared the 3 key similarities noted above. The Med-Plus incorporated legumes, fruits, and whole, intact grains, while the WFKD avoided them. The primary outcome was the percentage change in glycated hemoglobin (HbA1c) after 12 weeks on each diet. Secondary and exploratory outcomes included percentage changes in body weight, fasting insulin, glucose, and blood lipids; average glucose from continuous glucose monitor (CGM), and nutrient intake. RESULTS: The primary analysis was of 33 participants with complete data. The HbA1c values did not differ between diets at 12 weeks. Triglycerides decreased more for the WFKD [percentage changes, -16% (SEM, 4%) compared with -5% (SEM, 6%) for the Med-Plus; P = 0.02] and LDL cholesterol was higher for the WFKD [percentage changes, +10% (SEM, 4%) compared with -5% (SEM, 5%) for the Med-Plus; P = 0.01]. Weight decreased 8% (SEM, 1%) compared with 7% (SEM, 1%) and HDL cholesterol increased 11% (SEM, 2%) compared with 7% (SEM, 3%) for the WFKD compared with the Med-Plus, respectively; however, there was a significant interaction of diet × order for both. Participants had lower intakes of fiber and 3 nutrients on the WFKD compared with the Med-Plus. Twelve-week follow-up data suggest the Med-Plus is more sustainable. CONCLUSIONS: HbA1c values were not different between diet phases after 12 weeks, but improved from baseline on both diets, likely due to several shared dietary aspects. The WFKD led to a greater decrease in triglycerides, but also had potential untoward risks from elevated LDL cholesterol and lower nutrient intakes from avoiding legumes, fruits, and whole, intact grains, as well as being less sustainable. This trial was registered at clinicaltrials.gov as NCT03810378.

Classification of Common Food Lipid Sources Regarding Healthiness Using Advanced Lipidomics: A Four-Arm Crossover Study.

Prospective studies have failed to establish a causal relationship between animal fat intake and cardiovascular diseases in humans. Furthermore, the metabolic effects of different dietary sources remain unknown. In this four-arm crossover study, we investigated the impact of consuming cheese, beef, and pork meat on classic and new cardiovascular risk markers (obtained from lipidomics) in the context of a healthy diet. A total of 33 young healthy volunteers (23 women/10 men) were assigned to one out of four test diets in a Latin square design. Each test diet was consumed for 14 days, with a 2-week washout. Participants received a healthy diet plus Gouda- or Goutaler-type cheeses, pork, or beef meats. Before and after each diet, fasting blood samples were withdrawn. A reduction in total cholesterol and an increase in high density lipoprotein particle size were detected after all diets. Only the pork diet upregulated plasma unsaturated fatty acids and downregulated triglycerides species. Improvements in the lipoprotein profile and upregulation of circulating plasmalogen species were also observed after the pork diet. Our study suggests that, within the context of a healthy diet rich in micronutrients and fiber, the consumption of animal products, in particular pork meat, may not induce deleterious effects, and reducing the intake of animal products should not be regarded as a way of reducing cardiovascular risk in young individuals.

Overall and Sex-Specific Effect of Berberine for the Treatment of Dyslipidemia in Adults: A Systematic Review and Meta-Analysis of Randomized Placebo-Controlled Trials.

BACKGROUND: Berberine is a nutraceutical that can improve lipid metabolism. Berberine may also affect sex hormones and exert sex-specific lipid-modifying effects, which have been overlooked. This study aimed to comprehensively review the efficacy and safety of berberine in adults for the treatment of dyslipidemia with consideration of potential sex disparity. Data Sources We searched Medline, Embase, Wanfang, CNKI, ClinicalTrials.gov, and the WHO International Clinical Trials Registry Platform from inception to 13 December 2022. No language restrictions were applied. This study was registered in PROSPERO (CRD42021293218) prior to completing the literature search. Study Selection Two blinded reviewers assessed studies for inclusion. Eligible studies were randomized controlled trials in adults that compared berberine versus placebo, and measured blood lipids or lipoproteins. Data Extraction and Synthesis Data extraction was performed by two blinded reviewers using a structured form in Covidence. Risk of bias was assessed using the Cochrane risk of bias tool for randomized trials. Mean differences (MD) were estimated using inverse variance weighting with random effects models for lipid outcomes using R. Adverse events (AEs) were described narratively. Main Outcomes Primary outcomes were low-density lipoprotein (LDL) cholesterol, total cholesterol, triglycerides, high-density lipoprotein (HDL) cholesterol, and apolipoprotein B. Secondary outcomes were gastrointestinal and muscle-related AEs. RESULTS: Eighteen studies (n = 1788 participants), conducted mainly in mainland China and Hong Kong (15 studies [83%]), were included with treatment durations ranging from 4 to 24 weeks. Berberine reduced LDL cholesterol (- 0.46 mmol/L, 95% CI - 0.62 to - 0.30, 14 studies, n = 1447), total cholesterol (- 0.48 mmol/L, 95% CI - 0.63 to - 0.33, 17 studies, n = 1637), triglycerides (- 0.34 mmol/L, 95% CI - 0.46 to - 0.23, 18 studies, n = 1661) and apolipoprotein B (- 0.25 g/L, 95% CI - 0.40 to - 0.11, 2 studies, n = 127). Berberine increased HDL cholesterol by 0.06 mmol/L (95% CI 0.00 to 0.11, 15 studies, n = 1471). Notably, the effect on HDL cholesterol was different in women (0.11 mmol/L, 95% CI 0.09 to 0.13) from that in men (- 0.07 mmol/L, 95% CI - 0.16 to 0.02). Among 16 studies that reported AEs, no serious AEs were reported for berberine. Gastrointestinal AEs were reported in 12 studies and tended to be more frequent in participants allocated to berberine versus placebo (2-23% vs 2-15%). CONCLUSIONS: Berberine produces small reductions in LDL cholesterol, triglycerides, and apolipoprotein B, with potential sex-specific effects on HDL cholesterol. Large-scale trials that consider sex disparity and assess clinical outcomes are required.

Berberine is found naturally in barberry and goldenthread, plants which have long been used in traditional herbal medicine in Asia. Nowadays berberine is used as a purified product and is easy to purchase as a nutraceutical supplement or non-prescription drug. People with dyslipidemia, a medical condition often known as 'high cholesterol', may prefer treatment with a nutraceutical such as berberine to reduce blood cholesterol. In recent years, many studies have contrasted the effects of taking berberine with an inactive placebo. This study aimed to combine all the available randomized controlled trials that assessed berberine's effects on blood lipids and lipoproteins. We included 18 studies that used berberine doses of 900­1500 mg/day, the majority of which were conducted in mainland China and Hong Kong. We found that on average berberine can modestly reduce low-density lipoprotein (LDL) cholesterol by 0.5 mmol/L (18 mg/dL) and triglycerides by 0.3 mmol/L (30 mg/dL). Berberine also increases high-density lipoprotein (HDL) cholesterol by 0.06 mmol/L (2 mg/dL). Interestingly, women may obtain a greater increase in HDL cholesterol than men. The short-term use of berberine appears to be safe. No study participants treated with berberine experienced a serious adverse event. However, berberine may occasionally cause constipation, diarrhea, or nausea. Larger high-quality studies are still needed to determine the long-term effects of berberine for dyslipidemia.

Changes in clinic visits and diabetes and metabolic control in patients with type 2 diabetes during COVID-19 pandemic: A real world evidence.

PURPOSE: The study aim was to evaluate the effects of public lockdown during the covid-19 pandemic on glucose and metabolic parameters as well as body weight control in type 2 diabetic patients. METHODS: This study was conducted in two outpatient Diabetes Clinics and analyzed data available in database of Diabetes Clinic. Data related to a year before covid-19 pandemic and a year during covid-19 pandemic was collected from the database and analyzed. Patients with type 2 diabetes included in the analysis if they had referred to Diabetes Clinics both before and during covid-19 pandemic. Demographic information and data about metabolic status were collected from the records of previous outpatient Clinic visits and compared RESULTS: Finally 9440 patients with mean age of 61.08 ± 11.62 referred to Diabetes Clinics in both the year before and the year of the corona pandemic. Mean FBS and HbA1c in diabetes patients reduced significantly from 155.37 ± 62.93 and 7.97 ± 1.74 before pandemic, respectively to 138.77 ± 45.39 and 7.54 ± 1.34, respectively during covid-19 outbreak. During covid-19 pandemic, all metabolic parameters including glycemic and lipid profile (except for triglyceride) and BMI (body mass index) reduced significantly statistically, but, these changes were not clinically significant. However, triglyceride level increased statistically significantly but again it was not significant clinically. CONCLUSION: During COVID-19 lockdown, glycemic and metabolic control of diabetes patients have improved significantly except for triglycerides.

Predictors of New-Onset Diabetes in Hospitalized Patients with SARS-CoV-2 Infection.

The pandemic caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is one of the world's most disruptive health crises. The presence of diabetes plays an important role in the severity of the infection, and a rise in newly diagnosed diabetes cases has been identified. The aim of this retrospective study was to determine the incidence of new-onset diabetes (NOD) and predictive factors with their cut-off values for patients hospitalized with COVID-19. All patients (n = 219) hospitalized for COVID-19 during three consecutive months were included. NOD was diagnosed in 26.48% of patients. The severity of the infection, hospital admission values for fasting plasma glucose, lactate dehydrogenase (LDH), PaO2/FiO2 ratio, the peak values for leucocytes, neutrophils, C-reactive protein, triglycerides, and the need for care in the intensive care unit were predictors for the occurrence of NOD in univariate analysis, while only LDH level remained a significant predictor in the multivariable analysis. In conclusion, the results of the study showed a high incidence of NOD in patients hospitalized with COVID-19 and identified LDH levels at hospital admission as a significant predictor of NOD during SARS-CoV-2 infection. However, the persistence of NOD after the COVID-19 infection is not known, therefore, the results must be interpreted with caution.

Triglyceride Lowering with Pemafibrate to Reduce Cardiovascular Risk.

BACKGROUND: High triglyceride levels are associated with increased cardiovascular risk, but whether reductions in these levels would lower the incidence of cardiovascular events is uncertain. Pemafibrate, a selective peroxisome proliferator-activated receptor α modulator, reduces triglyceride levels and improves other lipid levels. METHODS: In a multinational, double-blind, randomized, controlled trial, we assigned patients with type 2 diabetes, mild-to-moderate hypertriglyceridemia (triglyceride level, 200 to 499 mg per deciliter), and high-density lipoprotein (HDL) cholesterol levels of 40 mg per deciliter or lower to receive pemafibrate (0.2-mg tablets twice daily) or matching placebo. Eligible patients were receiving guideline-directed lipid-lowering therapy or could not receive statin therapy without adverse effects and had low-density lipoprotein (LDL) cholesterol levels of 100 mg per deciliter or lower. The primary efficacy end point was a composite of nonfatal myocardial infarction, ischemic stroke, coronary revascularization, or death from cardiovascular causes. RESULTS: Among 10,497 patients (66.9% with previous cardiovascular disease), the median baseline fasting triglyceride level was 271 mg per deciliter, HDL cholesterol level 33 mg per deciliter, and LDL cholesterol level 78 mg per deciliter. The median follow-up was 3.4 years. As compared with placebo, the effects of pemafibrate on lipid levels at 4 months were -26.2% for triglycerides, -25.8% for very-low-density lipoprotein (VLDL) cholesterol, -25.6% for remnant cholesterol (cholesterol transported in triglyceride-rich lipoproteins after lipolysis and lipoprotein remodeling), -27.6% for apolipoprotein C-III, and 4.8% for apolipoprotein B. A primary end-point event occurred in 572 patients in the pemafibrate group and in 560 of those in the placebo group (hazard ratio, 1.03; 95% confidence interval, 0.91 to 1.15), with no apparent effect modification in any prespecified subgroup. The overall incidence of serious adverse events did not differ significantly between the groups, but pemafibrate was associated with a higher incidence of adverse renal events and venous thromboembolism and a lower incidence of nonalcoholic fatty liver disease. CONCLUSIONS: Among patients with type 2 diabetes, mild-to-moderate hypertriglyceridemia, and low HDL and LDL cholesterol levels, the incidence of cardiovascular events was not lower among those who received pemafibrate than among those who received placebo, although pemafibrate lowered triglyceride, VLDL cholesterol, remnant cholesterol, and apolipoprotein C-III levels. (Funded by the Kowa Research Institute; PROMINENT ClinicalTrials.gov number, NCT03071692.).

Systematic Review and Meta-Analysis of Telecoaching for Self-Care Management among Persons with Type 2 Diabetes Mellitus.

BACKGROUND: In response to the need for safe care for people with diabetes mellitus in the current outbreak of COVID-19, it is critical to evaluate the model, service delivery, feasibility, and efficiency of diabetes mellitus telecoaching. OBJECTIVE: This study aimed to conduct a systematic review and meta-analysis of the model and efficacy of telecoaching to improve self-care and clinical outcomes. METHODS: This study uses the Preferred Reporting Item for Systematic Review and Meta-Analysis (PRISMA). We searched on 22 March 2022, using keywords that matched the MeSH browser in four databases to find relevant studies, namely, PubMed/Medline, Proquest, Scopus, and EBSCOhost. Additionally, we collected randomized controlled trials (RCTs) on Google Scholar using the snowball technique. A quality assessment was performed using the Cochrane Collaboration's Risk of Bias tool (RoB)2. The meta-analysis used the DerSimonian-Laird random-effects model to analyze the pooled mean difference (MD) and its p-value. RESULTS: Thirteen RCT studies were included for the systematic review and meta-analysis with a total number of participants of 3300. The model of telecoaching is a form of using nurses-led telephone and mobile apps, which are relatively cost-effective. The meta-analysis showed a positively improved statistically significance in clinical outcomes, including in HbA1c (a pooled MD of -0.33; 95% CI: -0.51--0.15; p = 0.0003), blood glucose (-18.99; 95% CI: -20.89--17.09; p = 0.00001), systolic blood pressure (-2.66; 95% CI: -3.66--1.66; p = 0.00001), body mass index (-0.79; 95% CI: -1.39--0.18; p = 0.01), and weight (-2.16 kg; 95% CI: -3.95--0.38; p = 0.02). It was not, however, statistically significant in diastolic blood pressure (-0.87; 95% CI: -2.02-0.28; p = 0.14), total cholesterol (-0.07; 95% CI: -0.26-0.12; p = 0.46), low-density lipoprotein (-2.19; 95% CI: -6.70-2.31; p = 0.34), triglycerides (-13.56; 95% CI: -40.46-13.35; p = 0.32) and high-density protein (0.40; 95% CI: -1.12-1.91; p = 0.61). CONCLUSIONS: The telecoaching with nurses-led telephone and mobile apps significantly affected clinical outcomes on HbA1c, systolic blood pressure, weight, and BMI. Moreover, there was no significant effect on the total cholesterol, low-density lipoprotein, triglycerides, and high-density lipoprotein. Thus, telecoaching has the potential as a care model in diabetes mellitus during COVID-19 and similar pandemics to improve self-care and clinical outcomes, but all the studies analyzed involved non-COVID-19 patients, limiting the generalizability of the results to COVID-19.

Neurodevelopmental Outcomes in Preterm Infants Receiving a Multicomponent vs. a Soybean-Based Lipid Emulsion: 24 Month Follow-Up of a Randomized Controlled Trial.

BACKGROUND: Few studies in the literature have analyzed the long-term neurodevelopmental outcomes of the administration of a multicomponent versus a soybean-based lipid emulsion (LE) in preterm infants receiving parenteral nutrition (PN). A recent randomized controlled trial conducted in our unit provided evidence of better growth in head circumference during the hospital stay in those who received a multicomponent LE. METHODS: This is a 24 month follow-up study of preterm infants, previously enrolled in a randomized trial, who received a multicomponent LE (SMOFlipid®) or a standard soybean-based one (Intralipid®). We evaluated neurodevelopmental outcomes at 24 months of corrected age (CA) in the two groups. RESULTS: Ninety-three children were followed up to the age of 24 months CA. Due to the peculiar time frame of the SARS-CoV-2 pandemic, neurodevelopmental outcomes were evaluated only in 77 children: 37 in the SMOFlipid® group and 40 in the Intralipid® group. No differences in major disability rates or in Griffith's evaluation were found between the two groups. CONCLUSIONS: In our population study, the administration of a multicomponent LE containing fish oil, compared to a soybean-based LE, had no significant effects on neurodevelopmental outcomes in preterm infants at 24 months CA.

Update on Omega-3 Polyunsaturated Fatty Acids on Cardiovascular Health.

Twenty percent of deaths in the United States are secondary to cardiovascular diseases (CVD). In patients with hyperlipidemia and hypertriglyceridemia, studies have shown high atherosclerotic CVD (ASCVD) event rates despite the use of statins. Given the association of high triglyceride (TG) levels with elevated cholesterol and low levels of high-density lipoprotein cholesterol, the American Heart Association (AHA)/American College of Cardiology (ACC) cholesterol guidelines recommend using elevated TGs as a "risk-enhancing factor" for ASCVD and using omega 3 fatty acids (Ω3FAs) for patients with persistently elevated severe hypertriglyceridemia. Ω3FA, or fish oils (FOs), have been shown to reduce very high TG levels, hospitalizations, and CVD mortality in randomized controlled trials (RCTs). We have published the largest meta-analysis to date demonstrating significant effects on several CVD outcomes, especially fatal myocardial infarctions (MIs) and total MIs. Despite the most intensive research on Ω3FAs on CVD, their benefits have been demonstrated to cluster across multiple systems and pathologies, including autoimmune diseases, infectious diseases, chronic kidney disease, central nervous system diseases, and, most recently, the COVID-19 pandemic. A review and summary of the controversies surrounding Ω3FAs, some of the latest evidence-based findings, and the current and most updated recommendations on Ω3FAs are presented in this paper.

Shared genetic influences between blood analyte levels and risk of severe COVID-19.

Genome-wide association studies (GWASs) show that genetic factors contribute to the risk of severe coronavirus disease 2019 (COVID-19) and blood analyte levels. Here, we utilize GWAS summary statistics to study the shared genetic influences (pleiotropy) between severe COVID-19 and 344 blood analytes at the genome, gene, and single-nucleotide polymorphism (SNP) levels. Our pleiotropy analyses genetically link blood levels of 71 analytes to severe COVID-19 in at least one of the three levels of investigation-suggesting shared biological mechanisms or causal relationships. Six analytes (alanine aminotransferase, alkaline phosphatase, apolipoprotein B, C-reactive protein, triglycerides, and urate) display evidence of pleiotropy with severe COVID-19 at all three levels. Causality analyses indicate that higher triglycerides levels causally increase the risk of severe COVID-19, thereby providing important support for the use of lipid-lowering drugs such as statins and fibrates to prevent severe COVID-19.

Remnant cholesterol levels are associated with severity and death in COVID-19 patients.

Coronavirus disease-19 (COVID-19) patients with severe complications present comorbidities like cardiovascular-disease, hypertension and type-2 diabetes mellitus (DM), sharing metabolic alterations like insulin resistance (IR) and dyslipidemia. Our objective was to evaluate the association among different components of the lipid-lipoprotein profile, such as remnant lipoprotein (RLP)-cholesterol, in patients with COVID-19, and to analyze their associations with the severity of the disease and death. We studied 193 patients (68 (29-96) years; 49.7% male) hospitalized for COVID-19 and 200 controls (46 (18-79) years; 52.5% male). Lipoprotein profile, glucose and procalcitonin were assessed. Patients presented higher glucose, TG, TG/HDL-cholesterol and RLP-cholesterol levels, but lower total, LDL, HDL and no-HDL-cholesterol levels (p < 0.001). When a binary logistic regression was performed, age, non-HDL-cholesterol, and RLP-cholesterol were associated with death (p = 0.005). As the COVID-19 condition worsened, according to procalcitonin tertiles, a decrease in all the cholesterol fractions (p < 0.03) was observed with no differences in TG, while levels of RLP-cholesterol and TG/HDL-cholesterol increased (p < 0.001). Lower levels of all the cholesterol fractions were related with the presence and severity of COVID-19, except for RLP-cholesterol levels and TG/HDL-cholesterol index. These alterations indicate a lipid metabolic disorder, characteristic of IR states in COVID-19 patients. RLP-cholesterol levels predicted severity and death in these patients.

Machine Learning Sensors for Diagnosis of COVID-19 Disease Using Routine Blood Values for Internet of Things Application.

Healthcare digitalization requires effective applications of human sensors, when various parameters of the human body are instantly monitored in everyday life due to the Internet of Things (IoT). In particular, machine learning (ML) sensors for the prompt diagnosis of COVID-19 are an important option for IoT application in healthcare and ambient assisted living (AAL). Determining a COVID-19 infected status with various diagnostic tests and imaging results is costly and time-consuming. This study provides a fast, reliable and cost-effective alternative tool for the diagnosis of COVID-19 based on the routine blood values (RBVs) measured at admission. The dataset of the study consists of a total of 5296 patients with the same number of negative and positive COVID-19 test results and 51 routine blood values. In this study, 13 popular classifier machine learning models and the LogNNet neural network model were exanimated. The most successful classifier model in terms of time and accuracy in the detection of the disease was the histogram-based gradient boosting (HGB) (accuracy: 100%, time: 6.39 sec). The HGB classifier identified the 11 most important features (LDL, cholesterol, HDL-C, MCHC, triglyceride, amylase, UA, LDH, CK-MB, ALP and MCH) to detect the disease with 100% accuracy. In addition, the importance of single, double and triple combinations of these features in the diagnosis of the disease was discussed. We propose to use these 11 features and their binary combinations as important biomarkers for ML sensors in the diagnosis of the disease, supporting edge computing on Arduino and cloud IoT service.

The Social Distance Impacts from COVID-19 Pandemic on the Development of Two Orders of a Concurrent Training Programme for Morbidly Obese Patients.

BACKGROUND: Although there is relevant information regarding the consequences of the coronavirus SARS-CoV-2 (COVID-19), little is known about the impact of the imposed social confinement (at home) on the development of exercise training programmes in populations with morbid obesity. AIM: To describe the effects of the imposed COVID-19 confinement on the cardiometabolic health benefits acquired through a concurrent training programme that started before the pandemic in populations with morbid obesity. METHODS: This was an experimental randomized clinical study, in which sedentary morbidly obese women were assigned 1:1 to a high-intensity interval training (HIIT) plus resistance training (RT) group (HIIT + RT; n = 11; BMI 42.1 ± 6.6) or to the same exercise dose, but in different order group of RT plus HIIT group (RT + HIIT; n = 7; BMI 47.5 ± 8.4). Both groups undertook two sessions/week. When COVID-19 confinement at home started, a post-test was applied in January 2020 (Post1) and after 20 months (Post2). The main outcomes were waist circumference (WC), systolic (SBP) and diastolic blood pressure (DBP), high-density lipids (HDL-c), triglycerides (Tg), and fasting plasma glucose (FPG). RESULTS: In the HIIT + RT group, the WC showed significant increases from Post1 to Post2 (Δ + 3.1 cm, p = 0.035); in the RT + HIIT group, it decreased from Post1 to Post2 (Δ - 4.8 cm, p = 0.028). In the HIIT + RT group, SBP showed significant increases from Post1 to Post2 (Δ + 6.2 mmHg, p = 0.041); the RT + HIIT group decreased SBP from Pre0 to Post1 (Δ - 7.2 mmHg, p = 0.026) and increased DBP from Pre0 to Post1 (Δ + 8.1 mmHg, p = 0.015). Tg in the HIIT + RT group decreased from Pre0 to Post1 (Δ - 40.1 mg/dL, p = 0.023) but increased from Post1 to Post2 (Δ + 86.3 mg/dL, p < 0.0001). CONCLUSIONS: The COVID-19 social confinement worsened metabolic syndrome (MetS) outcomes that had improved from 20 weeks' RT + HIIT during the training period, such as WC, SBP, and Tg from HIIT + RT, when, worryingly, SBP increased to another more serious clinical classification in both groups.

A Single Oral Vitamin D3 Bolus Reduces Inflammatory Markers in Healthy Saudi Males.

Vitamin D deficiency has increased in the general population and is a public health issue. Vitamin D plays an important role in regulating the immune system, e.g., by modulating the production of inflammatory cytokines. In most countries, the recommended maximal daily dose of vitamin D3 is 4000 IU (100 µg) per day. In this study, we investigated whether a single vitamin D3 bolus can reduce the levels of the inflammatory markers interleukin (IL) 6, IL8 and tumor necrosis factor (TNF) within one month. Fifty healthy Saudi males were recruited from the local community in Jeddah city and were orally supplemented with a single dose of 80,000 IU vitamin D3. Serum samples were collected at time points 0, 1 and 30 days, and serum levels of IL6, IL8 and TNF, parathyroid hormone (PTH), 25-hydroxyvitamin D3 (25(OH)D3), triglycerides, cholesterol, calcium (Ca2+) and phosphate (PO4-) were determined. On average, the vitamin D3 bolus resulted in a significant increase in vitamin D status as well as in a significant decrease in the levels of inflammatory cytokines even one month after supplementation without changing serum Ca2+, PO4- or lipid levels. In conclusion, single high-dose vitamin D3 supplementation is safe for reducing inflammation markers and may lead to an update of current recommendations for vitamin D intake, in order to prevent critical health problems.

Prognostic value of the TyG index for in-hospital mortality in nondiabetic COVID-19 patients with myocardial injury.

OBJECTIVE: The purpose of this study was to explore the efficacy of the triglyceride glucose (TyG) index on in-hospital mortality in nondiabetic coronavirus disease 2019 (COVID-19) patients with myocardial injury. METHODS: This was a retrospective study, which included 218 nondiabetic COVID-19 patients who had myocardial injury. The TyG index was derived using the following equation: log [serum triglycerides (mg/dL) ×fasting blood glucose (mg/dL)/2]. RESULTS: Overall, 49 (22.4%) patients died during hospitalization. Patients who did not survive had a higher TyG index than survivors. In multivariate Cox regression analysis, it was found that the TyG index was independently associated with in-hospital death. A TyG index cutoff value greater than 4.97 was predicted in-hospital death in nondiabetic COVID-19 patients with myocardial damage, with 82% sensitivity and 66% specificity. A pairwise evaluation of receiver operating characteristic (ROC) curves demonstrated that the TyG index (AUC: 0.786) had higher discriminatory performance than both triglyceride (AUC: 0.738) and fasting blood glucose (AUC: 0.660) in predicting in-hospital mortality among these patients. CONCLUSIONS: The TyG index might be used to identify high-risk nondiabetic COVID-19 patients with myocardial damage.