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1.
Signal Transduct Target Ther ; 6(1): 427, 2021 12 16.
Article in English | MEDLINE | ID: covidwho-1585887

ABSTRACT

Abnormal glucose and lipid metabolism in COVID-19 patients were recently reported with unclear mechanism. In this study, we retrospectively investigated a cohort of COVID-19 patients without pre-existing metabolic-related diseases, and found new-onset insulin resistance, hyperglycemia, and decreased HDL-C in these patients. Mechanistically, SARS-CoV-2 infection increased the expression of RE1-silencing transcription factor (REST), which modulated the expression of secreted metabolic factors including myeloperoxidase, apelin, and myostatin at the transcriptional level, resulting in the perturbation of glucose and lipid metabolism. Furthermore, several lipids, including (±)5-HETE, (±)12-HETE, propionic acid, and isobutyric acid were identified as the potential biomarkers of COVID-19-induced metabolic dysregulation, especially in insulin resistance. Taken together, our study revealed insulin resistance as the direct cause of hyperglycemia upon COVID-19, and further illustrated the underlying mechanisms, providing potential therapeutic targets for COVID-19-induced metabolic complications.


Subject(s)
COVID-19/blood , Hyperglycemia/blood , Insulin Resistance , Lipid Metabolism , Lipids/blood , SARS-CoV-2/metabolism , Adult , Aged , Biomarkers/blood , COVID-19/complications , Female , Humans , Hyperglycemia/etiology , Male , Middle Aged , Retrospective Studies
2.
Viruses ; 13(12)2021 12 14.
Article in English | MEDLINE | ID: covidwho-1572667

ABSTRACT

Pre-existing comorbidities such as obesity or metabolic diseases can adversely affect the clinical outcome of COVID-19. Chronic metabolic disorders are globally on the rise and often a consequence of an unhealthy diet, referred to as a Western Diet. For the first time in the Syrian hamster model, we demonstrate the detrimental impact of a continuous high-fat high-sugar diet on COVID-19 outcome. We observed increased weight loss and lung pathology, such as exudate, vasculitis, hemorrhage, fibrin, and edema, delayed viral clearance and functional lung recovery, and prolonged viral shedding. This was accompanied by an altered, but not significantly different, systemic IL-10 and IL-6 profile, as well as a dysregulated serum lipid response dominated by polyunsaturated fatty acid-containing phosphatidylethanolamine, partially recapitulating cytokine and lipid responses associated with severe human COVID-19. Our data support the hamster model for testing restrictive or targeted diets and immunomodulatory therapies to mediate the adverse effects of metabolic disease on COVID-19.


Subject(s)
COVID-19 , Diet, High-Fat/adverse effects , Dietary Carbohydrates/adverse effects , Lipid Metabolism , Severity of Illness Index , Animals , COVID-19/pathology , Cricetinae , Cytokines/blood , Disease Models, Animal , Edema , Fibrin , Hemorrhage , Humans , Interleukin-10 , Interleukin-6 , Lipidomics , Lipids/blood , Liver/pathology , Lung/pathology , Male , Mesocricetus , Obesity , SARS-CoV-2 , Sugars , Vasculitis/pathology , Virus Shedding
3.
Sci Rep ; 11(1): 21633, 2021 11 04.
Article in English | MEDLINE | ID: covidwho-1503836

ABSTRACT

Although the serum lipidome is markedly affected by COVID-19, two unresolved issues remain: how the severity of the disease affects the level and the composition of serum lipids and whether serum lipidome analysis may identify specific lipids impairment linked to the patients' outcome. Sera from 49 COVID-19 patients were analyzed by untargeted lipidomics. Patients were clustered according to: inflammation (C-reactive protein), hypoxia (Horowitz Index), coagulation state (D-dimer), kidney function (creatinine) and age. COVID-19 patients exhibited remarkable and distinctive dyslipidemia for each prognostic factor associated with reduced defense against oxidative stress. When patients were clustered by outcome (7 days), a peculiar lipidome signature was detected with an overall increase of 29 lipid species, including-among others-four ceramide and three sulfatide species, univocally related to this analysis. Considering the lipids that were affected by all the prognostic factors, we found one sphingomyelin related to inflammation and viral infection of the respiratory tract and two sphingomyelins, that are independently related to patients' age, and they appear as candidate biomarkers to monitor disease progression and severity. Although preliminary and needing validation, this report pioneers the translation of lipidome signatures to link the effects of five critical clinical prognostic factors with the patients' outcomes.


Subject(s)
COVID-19/metabolism , Lipids/blood , Serum/chemistry , Adult , Aged , Biomarkers/blood , COVID-19/blood , Dyslipidemias/metabolism , Female , Humans , Italy , Lipidomics/methods , Lipids/analysis , Male , Middle Aged , Oxidative Stress/physiology , Prognosis , SARS-CoV-2/metabolism , SARS-CoV-2/pathogenicity , Sphingomyelins/blood
5.
PLoS One ; 16(9): e0257433, 2021.
Article in English | MEDLINE | ID: covidwho-1406755

ABSTRACT

Metabolic syndrome (MetS) is frequently associated with various health issues and is a major contributor to morbidity and mortality worldwide, particularly with its recent relevance to coronavirus disease 2019 (COVID-19). To combat its increasing prevalence in Southeast Asia, numerous intervention programs have been implemented. We conducted a scoping review on recent interventions to manage MetS among Southeast Asians using standard methodologies. Cochrane, Embase, Ovid MEDLINE, PubMed, and Scopus databases were systematically searched to yield peer-reviewed articles published between 2010-2020. We included 13 articles describing 11 unique interventions in four Southeast Asian countries: Malaysia, Thailand, Indonesia, and Vietnam. These interventions were broadly categorized into four groups: (i) nutrition (n = 4); (ii) physical activity (n = 2); (iii) nutrition and physical activity (n = 2); and (iv) multi-intervention (n = 3). Most studies investigated the effects of an intervention on components of MetS, which are anthropometry, blood pressure, glucose-related parameters, and lipid profile. Significant improvements ranged from 50% of studies reporting serum triglyceride and HDL-cholesterol levels to 100% for waist circumference. Evidence on interventions for individuals with MetS remains limited in Southeast Asia. More studies from other countries in this region are needed, especially on the effects of dietary interventions, to effectively address gaps in knowledge and provide sufficient data to design the ideal intervention for Southeast Asian populations.


Subject(s)
Metabolic Syndrome/epidemiology , Metabolic Syndrome/therapy , Asia, Southeastern/epidemiology , Diet , Humans , Life Style , Lipids/blood , Metabolic Syndrome/blood , Metabolic Syndrome/diet therapy
8.
Clin Chem Lab Med ; 59(12): 1891-1905, 2021 11 25.
Article in English | MEDLINE | ID: covidwho-1334799

ABSTRACT

Human Severe Acute Respiratory Syndrome CoronaVirus 2 (SARS-CoV-2) infection activates a complex interaction host/virus, leading to the reprogramming of the host metabolism aimed at the energy supply for viral replication. Alterations of the host metabolic homeostasis strongly influence the immune response to SARS-CoV-2, forming the basis of a wide range of outcomes, from the asymptomatic infection to the onset of COVID-19 and up to life-threatening acute respiratory distress syndrome, vascular dysfunction, multiple organ failure, and death. Deciphering the molecular mechanisms associated with the individual susceptibility to SARS-CoV-2 infection calls for a system biology approach; this strategy can address multiple goals, including which patients will respond effectively to the therapeutic treatment. The power of metabolomics lies in the ability to recognize endogenous and exogenous metabolites within a biological sample, measuring their concentration, and identifying perturbations of biochemical pathways associated with qualitative and quantitative metabolic changes. Over the last year, a limited number of metabolomics- and lipidomics-based clinical studies in COVID-19 patients have been published and are discussed in this review. Remarkable alterations in the lipid and amino acid metabolism depict the molecular phenotype of subjects infected by SARS-CoV-2; notably, structural and functional data on the lipids-virus interaction may open new perspectives on targeted therapeutic interventions. Several limitations affect most metabolomics-based studies, slowing the routine application of metabolomics. However, moving metabolomics from bench to bedside cannot imply the mere determination of a given metabolite panel; rather, slotting metabolomics into clinical practice requires the conversion of metabolic patient-specific data into actionable clinical applications.


Subject(s)
COVID-19/pathology , Metabolomics/methods , Amino Acids/analysis , Amino Acids/metabolism , COVID-19/epidemiology , COVID-19/virology , Cytokines/analysis , Eicosanoids/blood , Humans , Lipids/blood , Pandemics , Phenylalanine/analysis , Phenylalanine/metabolism , SARS-CoV-2/isolation & purification
9.
Virol J ; 18(1): 157, 2021 07 27.
Article in English | MEDLINE | ID: covidwho-1329116

ABSTRACT

BACKGROUND: The numbers of confirmed cases of coronavirus disease 2019 (COVID-19) and COVID-19 related deaths are still increasing, so it is very important to determine the risk factors of COVID-19. Dyslipidemia is a common complication in patients with COVID-19, but the association of dyslipidemia with the severity and mortality of COVID-19 is still unclear. The aim of this study is to analyze the potential association of dyslipidemia with the severity and mortality of COVID-19. METHODS: We searched the PubMed, Embase, MEDLINE, and Cochrane Library databases for all relevant studies up to August 24, 2020. All the articles published were retrieved without language restriction. All analysis was performed using Stata 13.1 software and Mantel-Haenszel formula with fixed effects models was used to compare the differences between studies. The Newcastle Ottawa scale was used to assess the quality of the included studies. RESULTS: Twenty-eight studies involving 12,995 COVID-19 patients were included in the meta-analysis, which was consisted of 26 cohort studies and 2 case-control studies. Dyslipidemia was associated with the severity of COVID-19 (odds ratio [OR] = 1.27, 95% confidence interval [CI] 1.11-1.44, P = 0.038, I2 = 39.8%). Further, patients with dyslipidemia had a 2.13-fold increased risk of death compared to patients without dyslipidemia (95% CI 1.84-2.47, P = 0.001, I2 = 66.4%). CONCLUSIONS: The results proved that dyslipidemia is associated with increased severity and mortality of COVID-19. Therefore, we should monitor blood lipids and administer active treatments in COVID-19 patients with dyslipidemia to reduce the severity and mortality.


Subject(s)
COVID-19/pathology , Dyslipidemias/pathology , Lipids/blood , Severity of Illness Index , COVID-19/mortality , Dyslipidemias/mortality , Humans , Risk Factors , SARS-CoV-2
10.
J Clin Lab Anal ; 35(8): e23911, 2021 Aug.
Article in English | MEDLINE | ID: covidwho-1308972

ABSTRACT

BACKGROUND: Dyslipidemia has been observed in patients with coronavirus disease 2019 (COVID-19). This study aimed to investigate blood lipid profiles in patients with COVID-19 and to explore their predictive values for COVID-19 severity. METHODS: A total of 142 consecutive patients with COVID-19 were included in this single-center retrospective study. Blood lipid profile characteristics were investigated in patients with COVID-19 in comparison with 77 age- and gender-matched healthy subjects, their predictive values for COVID-19 severity were analyzed by using multivariable logistic regression analysis, and their prediction efficiencies were evaluated by using receiver operator characteristic (ROC) curves. RESULTS: There were 125 and 17 cases in the non-severe and severe groups, respectively. Total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), and apolipoprotein A1 (ApoA1) gradually decreased across the groups in the following order: healthy controls, non-severe group, and severe group. ApoA1 was identified as an independent risk factor for COVID-19 severity (adjusted odds ratio [OR]: 0.865, 95% confidence interval [CI]: 0.800-0.935, p < 0.001), along with interleukin-6 (IL-6) (adjusted OR: 1.097, 95% CI: 1.034-1.165, p = 0.002). ApoA1 exhibited the highest area under the ROC curve (AUC) among all single markers (AUC: 0.896, 95% CI: 0.834-0.941); moreover, the risk model established using ApoA1 and IL-6 enhanced prediction efficiency (AUC: 0.977, 95% CI: 0.932-0.995). CONCLUSION: Blood lipid profiles in patients with COVID-19 are quite abnormal compared with those in healthy subjects, especially in severe cases. Serum ApoA1 may represent a good indicator for predicting the severity of COVID-19.


Subject(s)
Apolipoprotein A-I/blood , COVID-19/etiology , Adult , Aged , Area Under Curve , Biomarkers/blood , COVID-19/blood , COVID-19/epidemiology , Case-Control Studies , Cholesterol, HDL/blood , Cholesterol, LDL/blood , Comorbidity , Female , Humans , Lipids/blood , Male , Middle Aged , Retrospective Studies , Risk Factors , Severity of Illness Index
11.
Nutrients ; 13(7)2021 Jun 24.
Article in English | MEDLINE | ID: covidwho-1285398

ABSTRACT

OBJECTIVE: Vitamin D deficiency has been associated with an increased risk of COVID-19 severity. This multi-center randomized clinical trial aims to determine the effects of 5000 IU versus 1000 IU daily oral vitamin D3 supplementation in the recovery of symptoms and other clinical parameters among mild to moderate COVID-19 patients with sub-optimal vitamin D status. STUDY DESIGN AND SETTING: A total of 69 reverse transcriptase polymerase chain reaction (RT-PCR) SARS-CoV-2 positive adults who were hospitalized for mild to moderate COVID-19 disease were allocated to receive once daily for 2 weeks either 5000 IU oral vitamin D3 (n = 36, 21 males; 15 females) or 1000 IU oral vitamin D3 (standard control) (n = 33, 13 males; 20 females). Anthropometrics were measured and blood samples were taken pre- and post-supplementation. Fasting blood glucose, lipids, serum 25(OH)D, and inflammatory markers were measured. COVID-19 symptoms were noted on admission and monitored until full recovery. RESULTS: Vitamin D supplementation for 2 weeks caused a significant increase in serum 25(OH)D levels in the 5000 IU group only (adjusted p = 0.003). Within-group comparisons also showed a significant decrease in BMI and IL-6 levels overtime in both groups (p-values < 0.05) but was not clinically significant in between-group comparisons. Kaplan-Meier survival analysis revealed that the 5000 IU group had a significantly shorter time to recovery (days) than the 1000 IU group in resolving cough, even after adjusting for age, sex, baseline BMI, and D-dimer (6.2 ± 0.8 versus 9.1 ± 0.8; p = 0.039), and ageusia (loss of taste) (11.4 ± 1.0 versus 16.9 ± 1.7; p = 0.035). CONCLUSION: A 5000 IU daily oral vitamin D3 supplementation for 2 weeks reduces the time to recovery for cough and gustatory sensory loss among patients with sub-optimal vitamin D status and mild to moderate COVID-19 symptoms. The use of 5000 IU vitamin D3 as an adjuvant therapy for COVID-19 patients with suboptimal vitamin D status, even for a short duration, is recommended.


Subject(s)
COVID-19/drug therapy , Cholecalciferol/administration & dosage , Vitamins/administration & dosage , Administration, Oral , Adult , Aged , Blood Glucose/analysis , COVID-19/mortality , Dietary Supplements , Female , Hospitalization , Humans , Kaplan-Meier Estimate , Lipids/blood , Male , Middle Aged , Nutritional Status , SARS-CoV-2 , Saudi Arabia , Severity of Illness Index , Time Factors , Treatment Outcome , Vitamin D/blood , Vitamin D Deficiency/drug therapy
12.
Cell Death Dis ; 12(6): 541, 2021 05 25.
Article in English | MEDLINE | ID: covidwho-1243286

ABSTRACT

More and more patients suffered from Coronavirus disease 2019 (COVID-19) have got recovery gradually due to suitable intervention. Increasing data mainly studies the clinical characteristics of recovered COVID-19 patients, and their molecular changes especially proteome changes also play the same important role in understanding of biological characteristics of recovered COVID-19 patients as clinical characteristics do. In our study, we reported the whole lung-ground glass-CT value-average of mild/severe recovered patients 3 months after discharge without underlying diseases was significantly lower than that of healthy subjects. Then we isolated the extracellular vesicles (EVs) of plasma from 19 healthy subjects and 67 recovered COVID-19 patients. Mass Spectrometry was used to catalogue the proteins of these EVs compared to a defined group of controls. Identified 174 proteins were differentially expressed in the EVs of COVID-19 patients compared with healthy subjects, which involved in lipid metabolic process, response to cellular, and response to stress oxygen-containing compound. Besides, we identified several protein of plasma EVs in recovered patients associated with coagulation activity, inflammatory reaction, immune response, and low organ function. In addition, proteins correlating with clinical index such as alkaline phosphatase (ALP) and alanine aminotransferase (ALT) were also detected. Moreover, we also identified many unique or characteristic associations found in the recovered COVID-19 patients, which especially involved the kidney, serum electrolyte levels, and inflammation functions. This finding suggests that monitoring the situation of recovered patients might be useful, especially the indexes of coagulation, inflammation, immunity, and organ function, which can prevent bleeding, reinfection and organ dysfunction.


Subject(s)
COVID-19/metabolism , Convalescence , Extracellular Vesicles/metabolism , Adult , COVID-19/blood , COVID-19/pathology , COVID-19/physiopathology , Extracellular Vesicles/pathology , Female , Humans , Lipids/blood , Male , Middle Aged , Prospective Studies , Proteins/metabolism , Proteomics , SARS-CoV-2 , Severity of Illness Index
13.
Elife ; 102021 05 04.
Article in English | MEDLINE | ID: covidwho-1215707

ABSTRACT

Biomarkers of low-grade inflammation have been associated with susceptibility to a severe infectious disease course, even when measured prior to disease onset. We investigated whether metabolic biomarkers measured by nuclear magnetic resonance (NMR) spectroscopy could be associated with susceptibility to severe pneumonia (2507 hospitalised or fatal cases) and severe COVID-19 (652 hospitalised cases) in 105,146 generally healthy individuals from UK Biobank, with blood samples collected 2007-2010. The overall signature of metabolic biomarker associations was similar for the risk of severe pneumonia and severe COVID-19. A multi-biomarker score, comprised of 25 proteins, fatty acids, amino acids, and lipids, was associated equally strongly with enhanced susceptibility to severe COVID-19 (odds ratio 2.9 [95%CI 2.1-3.8] for highest vs lowest quintile) and severe pneumonia events occurring 7-11 years after blood sampling (2.6 [1.7-3.9]). However, the risk for severe pneumonia occurring during the first 2 years after blood sampling for people with elevated levels of the multi-biomarker score was over four times higher than for long-term risk (8.0 [4.1-15.6]). If these hypothesis generating findings on increased susceptibility to severe pneumonia during the first few years after blood sampling extend to severe COVID-19, metabolic biomarker profiling could potentially complement existing tools for identifying individuals at high risk. These results provide novel molecular understanding on how metabolic biomarkers reflect the susceptibility to severe COVID-19 and other infections in the general population.


National policies for mitigating the COVID-19 pandemic include stricter measures for people considered to be at high risk of severe and potentially fatal cases of the disease. Although older age and pre-existing health conditions are strong risk factors, it is poorly understood why susceptibility varies so widely in the population. People with cardiometabolic diseases, such as diabetes and liver diseases, or chronic inflammation are at higher risk of severe COVID-19 and other infections including pneumonia. These conditions alter the molecules circulating in the blood, providing potential 'biomarkers' to determine whether a person is more likely to develop a fatal infection. Uncovering these blood biomarkers could help to identify people who are prone to life-threatening infections despite not having ever been diagnosed with a cardiometabolic disease. To find these biomarkers, Julkunen et al. studied blood samples that had been collected from 105,000 healthy individuals in the United Kingdom over ten years ago. The data showed that individuals with biomarkers linked to low-grade inflammation and cardiometabolic disease were more likely to have died or been hospitalised with pneumonia. A score based on 25 of these biomarkers provided the best predictor of severe pneumonia. This biomarker score performed up to four times better within the first few years after blood sampling compared to predicting cases of pneumonia a decade later. The same blood biomarker changes were also linked with developing severe COVID-19 over ten years after the blood samples had been collected. The predictive value of the biomarker score was similar for both severe COVID-19 and the long-term risk of severe pneumonia. Julkunen et al. propose that the metabolic biomarkers reflect inhibited immunity that impairs response to infections. The results from over 100,000 individuals suggest that these blood biomarkers may help to identify people at high risk of severe COVID-19 or other infectious diseases.


Subject(s)
COVID-19/blood , Metabolome , Amino Acids/blood , Biomarkers/blood , COVID-19/epidemiology , Fatty Acids/blood , Humans , Lipids/blood , Magnetic Resonance Spectroscopy , Mass Screening/statistics & numerical data
14.
AIDS Res Hum Retroviruses ; 37(4): 297-303, 2021 04.
Article in English | MEDLINE | ID: covidwho-1207217

ABSTRACT

In the era of COVID-19, providers are delaying laboratory testing in people with HIV (PWH). The purpose of this study was to examine the clinical significance of renal, liver, and lipid testing. We reviewed the charts of 261 PWH who initiated care at an academic HIV clinic between January 1, 2016 and December 21, 2018. Analysis included one-sided binomial exact tests and multiple linear, Poisson, and Beta regression models. The most common abnormality was a glomerular filtration rate (GFR) <60 mL/min (10%). Age <40 years [estimated relative rate (rr) 0.017, 95% confidence interval (CI) 0.207 to 0.494], cobicistat (rr 0.284, 95% CI 0.128 to 0.63), and tenofovir alafenamide (rr 0.295 95% CI 0.151 to 0.573) were associated with a decreased risk of GFR <60 mL/min. An increased AST and ALT ≥2 × upper limit of normal (ULN) was found in 5% and 3%, respectively. Hepatitis C and use of darunavir and lopinavir were associated with increased AST or ALT. When a GFR was <60 mL/min or an AST or ALT was ≥2 × ULN, no action was taken in 53% of cases. In 18% of cases the only intervention was repeat testing. The most common interventions after lipid results were calculation of a 10-year cardiovascular risk score (31%) and addition of a statin (18%). Taking action after lipid results was strongly associated with age ≥40 (rr 7.37, 95% CI 3.0 to 18.3). Young PWH without hepatitis C rarely have renal, liver, or lipid test results that alter clinical care. Decreased testing should be considered.


Subject(s)
Antiviral Agents/therapeutic use , COVID-19/epidemiology , Drug Monitoring/methods , HIV Infections/drug therapy , Adult , Aged , Female , Glomerular Filtration Rate , HIV Infections/physiopathology , Humans , Lipids/blood , Liver Function Tests , Male , Middle Aged , Young Adult
15.
Front Endocrinol (Lausanne) ; 12: 651009, 2021.
Article in English | MEDLINE | ID: covidwho-1190304

ABSTRACT

Introduction: Patients with severe COVID-19 infections have coagulation abnormalities indicative of a hypercoagulable state, with thromboembolic complications and increased mortality. Platelets are recognized as mediators of inflammation, releasing proinflammatory and prothrombotic factors, and are hyperactivated in COVID-19 infected patients. Activated platelets have also been reported in type 2 diabetes (T2D) patients, putting these patients at higher risk for thromboembolic complications of COVID-19 infection. Methods: A case-control study of T2D (n=33) and control subjects (n=30) who underwent a hyperinsulinemic clamp to induce normoglycemia in T2D subjects: T2D: baseline glucose 7.5 ± 0.3mmol/l (135.1 ± 5.4mg/dl), reduced to 4.5 ± 0.07mmol/l (81 ± 1.2mg/dl) with 1-hour clamp; Controls: maintained at 5.1 ± 0.1mmol/l (91.9 ± 1.8mg/dl). Slow Off-rate Modified Aptamer (SOMA)-scan plasma protein measurement was used to determine a panel of platelet proteins. Results: Prothrombotic platelet proteins were elevated in T2D versus controls: platelet factor 4 (PF4, p<0.05); platelet glycoprotein VI (PGVI p<0.05); P-selectin (p<0.01) and plasminogen activator inhibitor I (PAI-1, p<0.01). In addition, the antithrombotic platelet-related proteins, plasmin (p<0.05) and heparin cofactor II (HCFII, p<0.05), were increased in T2D. Normalization of glucose in the T2D cohort had no effect on platelet protein levels. Conclusion: T2D patients have platelet hyperactivation, placing them at higher risk for thromboembolic events. When infected with COVID-19, this risk may be compounded, and their propensity for a more severe COVID-19 disease course increased. Clinical Trial Registration: https://clinicaltrials.gov/ct2/show/NCT03102801, identifier NCT03102801.


Subject(s)
Blood Platelet Disorders/blood , Blood Platelet Disorders/etiology , Blood Platelets/chemistry , Blood Proteins/analysis , COVID-19/blood , Diabetes Mellitus, Type 2/blood , Diabetes Mellitus, Type 2/complications , Hypoglycemia/blood , Hypoglycemia/complications , Aged , COVID-19/complications , Case-Control Studies , Female , Glucose Clamp Technique , Humans , Lipids/blood , Male , Middle Aged , Platelet Activation , Thromboembolism/blood , Thromboembolism/etiology
16.
Gut ; 70(7): 1253-1265, 2021 07.
Article in English | MEDLINE | ID: covidwho-1166535

ABSTRACT

OBJECTIVE: To characterise the oral microbiome, gut microbiome and serum lipid profiles in patients with active COVID-19 and recovered patients; evaluate the potential of the microbiome as a non-invasive biomarker for COVID-19; and explore correlations between the microbiome and lipid profile. DESIGN: We collected and sequenced 392 tongue-coating samples, 172 faecal samples and 155 serum samples from Central China and East China. We characterised microbiome and lipid molecules, constructed microbial classifiers in discovery cohort and verified their diagnostic potential in 74 confirmed patients (CPs) from East China and 37 suspected patients (SPs) with IgG positivity. RESULTS: Oral and faecal microbial diversity was significantly decreased in CPs versus healthy controls (HCs). Compared with HCs, butyric acid-producing bacteria were decreased and lipopolysaccharide-producing bacteria were increased in CPs in oral cavity. The classifiers based on 8 optimal oral microbial markers (7 faecal microbial markers) achieved good diagnostic efficiency in different cohorts. Importantly, diagnostic efficacy reached 87.24% in the cross-regional cohort. Moreover, the classifiers successfully diagnosed SPs with IgG antibody positivity as CPs, and diagnostic efficacy reached 92.11% (98.01% of faecal microbiome). Compared with CPs, 47 lipid molecules, including sphingomyelin (SM)(d40:4), SM(d38:5) and monoglyceride(33:5), were depleted, and 122 lipid molecules, including phosphatidylcholine(36:4p), phosphatidylethanolamine (PE)(16:0p/20:5) and diglyceride(20:1/18:2), were enriched in confirmed patients recovery. CONCLUSION: This study is the first to characterise the oral microbiome in COVID-19, and oral microbiomes and lipid alterations in recovered patients, to explore their correlations and to report the successful establishment and validation of a diagnostic model for COVID-19.


Subject(s)
COVID-19/blood , COVID-19/microbiology , Feces/microbiology , Lipids/blood , Mouth/microbiology , Adult , COVID-19/diagnosis , Case-Control Studies , China , Cohort Studies , Female , Gastrointestinal Microbiome , Humans , Lipidomics , Male , Middle Aged
17.
Sci Rep ; 11(1): 7217, 2021 03 30.
Article in English | MEDLINE | ID: covidwho-1160169

ABSTRACT

Lipids are indispensable in the SARS-CoV-2 infection process. The clinical significance of plasma lipid profile during COVID-19 has not been rigorously evaluated. We aim to ascertain the association of the plasma lipid profile with SARS-CoV-2 infection clinical evolution. Observational cross-sectional study including 1411 hospitalized patients with COVID-19 and an available standard lipid profile prior (n: 1305) or during hospitalization (n: 297). The usefulness of serum total, LDL, non-HDL and HDL cholesterol to predict the COVID-19 prognosis (severe vs mild) was analysed. Patients with severe COVID-19 evolution had lower HDL cholesterol and higher triglyceride levels before the infection. The lipid profile measured during hospitalization also showed that a severe outcome was associated with lower HDL cholesterol levels and higher triglycerides. HDL cholesterol and triglyceride concentrations were correlated with ferritin and D-dimer levels but not with CRP levels. The presence of atherogenic dyslipidaemia during the infection was strongly and independently associated with a worse COVID-19 infection prognosis. The low HDL cholesterol and high triglyceride concentrations measured before or during hospitalization are strong predictors of a severe course of the disease. The lipid profile should be considered as a sensitive marker of inflammation and should be measured in patients with COVID-19.


Subject(s)
COVID-19/etiology , Cholesterol, HDL/blood , Triglycerides/blood , Aged , COVID-19/blood , Female , Ferritins/blood , Fibrin Fibrinogen Degradation Products/analysis , Hospitalization , Humans , Lipids/blood , Male , Middle Aged , Severity of Illness Index
18.
Biosci Rep ; 41(3)2021 03 26.
Article in English | MEDLINE | ID: covidwho-1149758

ABSTRACT

BACKGROUND: The pandemic of novel coronavirus disease 2019 (COVID-19) has become a serious public health crisis worldwide. The symptoms of COVID-19 vary from mild to severe among different age groups, but the physiological changes related to COVID-19 are barely understood. METHODS: In the present study, a high-resolution mass spectrometry (HRMS)-based lipidomic strategy was used to characterize the endogenous plasma lipids for cured COVID-19 patients with different ages and symptoms. These patients were further divided into two groups: those with severe symptoms or who were elderly and relatively young patients with mild symptoms. In addition, automated lipidomic identification and alignment was conducted by LipidSearch software. Multivariate and univariate analyses were used for differential comparison. RESULTS: Nearly 500 lipid compounds were identified in each cured COVID-19 group through LipidSearch software. At the level of lipid subclasses, patients with severe symptoms or elderly patients displayed dramatic changes in plasma lipidomic alterations, such as increased triglycerides and decreased cholesteryl esters (ChE). Some of these differential lipids might also have essential biological functions. Furthermore, the differential analysis of plasma lipids among groups was performed to provide potential prognostic indicators, and the change in signaling pathways. CONCLUSIONS: Dyslipidemia was observed in cured COVID-19 patients due to the viral infection and medical treatment, and the discharged patients should continue to undergo consolidation therapy. This work provides valuable knowledge about plasma lipid markers and potential therapeutic targets of COVID-19 and essential resources for further research on the pathogenesis of COVID-19.


Subject(s)
COVID-19/blood , Dyslipidemias/epidemiology , Lipids/blood , Adolescent , Adult , Aged , Case-Control Studies , Chromatography, High Pressure Liquid , Female , Humans , Lipidomics , Male , Mass Spectrometry , Middle Aged , Plasma , Survivors , Young Adult
19.
AIDS Res Hum Retroviruses ; 37(4): 297-303, 2021 04.
Article in English | MEDLINE | ID: covidwho-1146081

ABSTRACT

In the era of COVID-19, providers are delaying laboratory testing in people with HIV (PWH). The purpose of this study was to examine the clinical significance of renal, liver, and lipid testing. We reviewed the charts of 261 PWH who initiated care at an academic HIV clinic between January 1, 2016 and December 21, 2018. Analysis included one-sided binomial exact tests and multiple linear, Poisson, and Beta regression models. The most common abnormality was a glomerular filtration rate (GFR) <60 mL/min (10%). Age <40 years [estimated relative rate (rr) 0.017, 95% confidence interval (CI) 0.207 to 0.494], cobicistat (rr 0.284, 95% CI 0.128 to 0.63), and tenofovir alafenamide (rr 0.295 95% CI 0.151 to 0.573) were associated with a decreased risk of GFR <60 mL/min. An increased AST and ALT ≥2 × upper limit of normal (ULN) was found in 5% and 3%, respectively. Hepatitis C and use of darunavir and lopinavir were associated with increased AST or ALT. When a GFR was <60 mL/min or an AST or ALT was ≥2 × ULN, no action was taken in 53% of cases. In 18% of cases the only intervention was repeat testing. The most common interventions after lipid results were calculation of a 10-year cardiovascular risk score (31%) and addition of a statin (18%). Taking action after lipid results was strongly associated with age ≥40 (rr 7.37, 95% CI 3.0 to 18.3). Young PWH without hepatitis C rarely have renal, liver, or lipid test results that alter clinical care. Decreased testing should be considered.


Subject(s)
Antiviral Agents/therapeutic use , COVID-19/epidemiology , Drug Monitoring/methods , HIV Infections/drug therapy , Adult , Aged , Female , Glomerular Filtration Rate , HIV Infections/physiopathology , Humans , Lipids/blood , Liver Function Tests , Male , Middle Aged , Young Adult
20.
N Engl J Med ; 384(11): 989, 2021 03 18.
Article in English | MEDLINE | ID: covidwho-1139778

ABSTRACT

BACKGROUND: Obesity is a global health challenge with few pharmacologic options. Whether adults with obesity can achieve weight loss with once-weekly semaglutide at a dose of 2.4 mg as an adjunct to lifestyle intervention has not been confirmed. METHODS: In this double-blind trial, we enrolled 1961 adults with a body-mass index (the weight in kilograms divided by the square of the height in meters) of 30 or greater (≥27 in persons with ≥1 weight-related coexisting condition), who did not have diabetes, and randomly assigned them, in a 2:1 ratio, to 68 weeks of treatment with once-weekly subcutaneous semaglutide (at a dose of 2.4 mg) or placebo, plus lifestyle intervention. The coprimary end points were the percentage change in body weight and weight reduction of at least 5%. The primary estimand (a precise description of the treatment effect reflecting the objective of the clinical trial) assessed effects regardless of treatment discontinuation or rescue interventions. RESULTS: The mean change in body weight from baseline to week 68 was -14.9% in the semaglutide group as compared with -2.4% with placebo, for an estimated treatment difference of -12.4 percentage points (95% confidence interval [CI], -13.4 to -11.5; P<0.001). More participants in the semaglutide group than in the placebo group achieved weight reductions of 5% or more (1047 participants [86.4%] vs. 182 [31.5%]), 10% or more (838 [69.1%] vs. 69 [12.0%]), and 15% or more (612 [50.5%] vs. 28 [4.9%]) at week 68 (P<0.001 for all three comparisons of odds). The change in body weight from baseline to week 68 was -15.3 kg in the semaglutide group as compared with -2.6 kg in the placebo group (estimated treatment difference, -12.7 kg; 95% CI, -13.7 to -11.7). Participants who received semaglutide had a greater improvement with respect to cardiometabolic risk factors and a greater increase in participant-reported physical functioning from baseline than those who received placebo. Nausea and diarrhea were the most common adverse events with semaglutide; they were typically transient and mild-to-moderate in severity and subsided with time. More participants in the semaglutide group than in the placebo group discontinued treatment owing to gastrointestinal events (59 [4.5%] vs. 5 [0.8%]). CONCLUSIONS: In participants with overweight or obesity, 2.4 mg of semaglutide once weekly plus lifestyle intervention was associated with sustained, clinically relevant reduction in body weight. (Funded by Novo Nordisk; STEP 1 ClinicalTrials.gov number, NCT03548935).


Subject(s)
Anti-Obesity Agents/administration & dosage , Glucagon-Like Peptide 1/agonists , Glucagon-Like Peptides/administration & dosage , Obesity/drug therapy , Adult , Anti-Obesity Agents/adverse effects , Body Composition/drug effects , Body Mass Index , Cholelithiasis/chemically induced , Diarrhea/chemically induced , Double-Blind Method , Female , Glucagon-Like Peptides/adverse effects , Healthy Lifestyle , Humans , Injections, Subcutaneous , Lipids/blood , Male , Middle Aged , Nausea/chemically induced , Obesity/complications , Prediabetic State/complications , Weight Loss/drug effects
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