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1.
BMC Med Genomics ; 14(1): 269, 2021 11 13.
Article in English | MEDLINE | ID: covidwho-1515444

ABSTRACT

BACKGROUND: As the number of COVID-19 deaths continues to rise worldwide, the identification of risk factors for the disease is an urgent issue, and it remains controversial whether atherogenic lipid-related traits including serum apolipoprotein B, low-density lipoprotein (LDL)-cholesterol, and triglyceride levels, are risk factors. The aim of this study was to estimate causal effects of lipid-related traits on COVID-19 risk in the European population using a two-sample Mendelian randomization (MR) approach. METHODS: We used summary statistics from a genome-wide association study (GWAS) that included 441,016 participants from the UK Biobank as the exposure dataset of lipid-related traits and from COVID-19 Host Genetics Initiative GWAS meta-analyses of European ancestry as the outcome dataset for COVID-19 susceptibility (32,494 cases and 1,316,207 controls), hospitalization (8316 cases and 1,549,095 controls), and severity (4792 cases and 1,054,664 controls). We performed two-sample MR analyses using the inverse variance weighted (IVW) method. As sensitivity analyses, the MR-Egger regression, weighted median, and weighted mode methods were conducted as were leave-one-out sensitivity analysis, the MR-PRESSO global test, PhenoScanner searches, and IVW multivariable MR analyses. A P value below 0.0055 with Bonferroni correction was considered statistically significant. RESULTS: This MR study suggested that serum apolipoprotein B or LDL-cholesterol levels were not significantly associated with COVID-19 risk. On the other hand, we inferred that higher serum triglyceride levels were suggestively associated with higher risks of COVID-19 susceptibility (odds ratio [OR] per standard deviation increase in lifelong triglyceride levels, 1.065; 95% confidence interval [CI], 1.001-1.13; P = 0.045) and hospitalization (OR, 1.174; 95% CI, 1.04-1.33; P = 0.012), and were significantly associated with COVID-19 severity (OR, 1.274; 95% CI, 1.08-1.50; P = 0.004). Sensitivity and bidirectional MR analyses suggested that horizontal pleiotropy and reverse causation were unlikely. CONCLUSIONS: Our MR study indicates a causal effect of higher serum triglyceride levels on a greater risk of COVID-19 severity in the European population using the latest and largest GWAS datasets to date. However, as the underlying mechanisms remain unclear and our study might be still biased due to possible horizontal pleiotropy, further studies are warranted to validate our findings and investigate underlying mechanisms.


Subject(s)
Apolipoprotein B-100 , COVID-19 , Cholesterol, LDL , Genetic Predisposition to Disease , Quantitative Trait, Heritable , SARS-CoV-2/metabolism , Triglycerides , Apolipoprotein B-100/blood , Apolipoprotein B-100/genetics , COVID-19/blood , COVID-19/genetics , Cholesterol, LDL/blood , Cholesterol, LDL/genetics , Female , Genome-Wide Association Study , Humans , Male , Mendelian Randomization Analysis , Risk Factors , Severity of Illness Index , Triglycerides/blood , Triglycerides/genetics
2.
NMR Biomed ; 35(2): e4637, 2022 02.
Article in English | MEDLINE | ID: covidwho-1487509

ABSTRACT

COVID-19 is a systemic infectious disease that may affect many organs, accompanied by a measurable metabolic dysregulation. The disease is also associated with significant mortality, particularly among the elderly, patients with comorbidities, and solid organ transplant recipients. Yet, the largest segment of the patient population is asymptomatic, and most other patients develop mild to moderate symptoms after SARS-CoV-2 infection. Here, we have used NMR metabolomics to characterize plasma samples from a cohort of the abovementioned group of COVID-19 patients (n = 69), between 3 and 10 months after diagnosis, and compared them with a set of reference samples from individuals never infected by the virus (n = 71). Our results indicate that half of the patient population show abnormal metabolism including porphyrin levels and altered lipoprotein profiles six months after the infection, while the other half show little molecular record of the disease. Remarkably, most of these patients are asymptomatic or mild COVID-19 patients, and we hypothesize that this is due to a metabolic reflection of the immune response stress.


Subject(s)
COVID-19/metabolism , Lipidomics , Magnetic Resonance Spectroscopy/methods , Metabolomics , SARS-CoV-2 , COVID-19/immunology , Cholesterol, HDL/blood , Cholesterol, LDL/blood , Humans
4.
Am J Clin Dermatol ; 22(5): 693-707, 2021 Sep.
Article in English | MEDLINE | ID: covidwho-1361347

ABSTRACT

BACKGROUND: Pivotal phase III studies demonstrated that abrocitinib, an oral, once-daily, JAK1-selective inhibitor, is effective treatment for moderate-to-severe atopic dermatitis (AD) as monotherapy and in combination with topical therapy. OBJECTIVE: The aim of this study was to evaluate the long-term safety of abrocitinib 200 mg and 100 mg in an integrated analysis of a phase IIb study, four phase III studies, and one long-term extension study. METHODS: Two cohorts were analyzed: a placebo-controlled cohort from 12- to 16-week studies and an all-abrocitinib cohort including patients who received one or more abrocitinib doses. Adverse events (AEs) of interest and laboratory data are reported. RESULTS: Total exposure in the all-abrocitinib cohort (n = 2856) was 1614 patient-years (PY); exposure was ≥ 24 weeks in 1248 patients and ≥ 48 weeks in 606 (maximum 108 weeks). In the placebo-controlled cohort (n = 1540), dose-related AEs (200 mg, 100 mg, placebo) were nausea (14.6%, 6.1%, 2.0%), headache (7.8%, 5.9%, 3.5%), and acne (4.7%, 1.6%, 0%). Platelet count was reduced transiently in a dose-dependent manner; 2/2718 patients (200-mg group) had confirmed platelet counts of < 50 × 103/mm3 at week 4. Incidence rates (IRs) were 2.33/100PY and 2.65/100 PY for serious infection, 4.34/100PY and 2.04/100PY for herpes zoster, and 11.83/100PY and 8.73/100PY for herpes simplex in the 200-mg and 100-mg groups, respectively. IRs for nonmelanoma skin cancer, other malignancies, and major adverse cardiovascular events were < 0.5/100PY for both doses. Five venous thromboembolism events occurred (IR 0.30/100PY), all in the 200-mg group. There were three deaths due to gastric carcinoma (diagnosed at day 43), sudden death, and COVID-19. CONCLUSION: Abrocitinib, with proper patient and dose selection, has a manageable tolerability and longer-term safety profile appropriate for long-term use in patients with moderate-to-severe AD. TRIAL REGISTRIES: ClinicalTrials.gov: NCT02780167, NCT03349060, NCT03575871, NCT03720470, NCT03627767, NCT03422822.


Subject(s)
Dermatitis, Atopic/drug therapy , Infections/epidemiology , Protein Kinase Inhibitors/adverse effects , Pyrimidines/adverse effects , Skin Neoplasms/epidemiology , Sulfonamides/adverse effects , Acne Vulgaris/chemically induced , Adolescent , Adult , Aged , Cardiovascular Diseases/epidemiology , Cholesterol, HDL/blood , Cholesterol, LDL/blood , Female , Headache/chemically induced , Herpes Simplex/epidemiology , Herpes Zoster/epidemiology , Humans , Incidence , Lymphocyte Count , Male , Middle Aged , Nausea/chemically induced , Platelet Count , Protein Kinase Inhibitors/administration & dosage , Pyrimidines/administration & dosage , Risk Factors , Sulfonamides/administration & dosage , Time Factors , Venous Thromboembolism/epidemiology , Young Adult
5.
Am J Clin Nutr ; 114(5): 1655-1665, 2021 11 08.
Article in English | MEDLINE | ID: covidwho-1349771

ABSTRACT

BACKGROUND: Angiotensin-converting enzyme 2 (ACE2) serves protective functions in metabolic, cardiovascular, renal, and pulmonary diseases and is linked to COVID-19 pathology. The correlates of temporal changes in soluble ACE2 (sACE2) remain understudied. OBJECTIVES: We explored the associations of sACE2 with metabolic health and proteome dynamics during a weight loss diet intervention. METHODS: We analyzed 457 healthy individuals (mean ± SD age: 39.8 ± 6.6 y) with BMI 28-40 kg/m2 in the DIETFITS (Diet Intervention Examining the Factors Interacting with Treatment Success) study. Biochemical markers of metabolic health and 236 proteins were measured by Olink CVDII, CVDIII, and Inflammation I arrays at baseline and at 6 mo during the dietary intervention. We determined clinical and routine biochemical correlates of the diet-induced change in sACE2 (ΔsACE2) using stepwise linear regression. We combined feature selection models and multivariable-adjusted linear regression to identify protein dynamics associated with ΔsACE2. RESULTS: sACE2 decreased on average at 6 mo during the diet intervention. Stronger decline in sACE2 during the diet intervention was independently associated with female sex, lower HOMA-IR and LDL cholesterol at baseline, and a stronger decline in HOMA-IR, triglycerides, HDL cholesterol, and fat mass. Participants with decreasing HOMA-IR (OR: 1.97; 95% CI: 1.28, 3.03) and triglycerides (OR: 2.71; 95% CI: 1.72, 4.26) had significantly higher odds for a decrease in sACE2 during the diet intervention than those without (P ≤ 0.0073). Feature selection models linked ΔsACE2 to changes in α-1-microglobulin/bikunin precursor, E-selectin, hydroxyacid oxidase 1, kidney injury molecule 1, tyrosine-protein kinase Mer, placental growth factor, thrombomodulin, and TNF receptor superfamily member 10B. ΔsACE2 remained associated with these protein changes in multivariable-adjusted linear regression. CONCLUSIONS: Decrease in sACE2 during a weight loss diet intervention was associated with improvements in metabolic health, fat mass, and markers of angiotensin peptide metabolism, hepatic and vascular injury, renal function, chronic inflammation, and oxidative stress. Our findings may improve the risk stratification, prevention, and management of cardiometabolic complications.This trial was registered at clinicaltrials.gov as NCT01826591.


Subject(s)
Angiotensin-Converting Enzyme 2/metabolism , Body Composition , COVID-19/metabolism , Diet, Reducing , Obesity/metabolism , Proteome/metabolism , Weight Loss/physiology , Adipose Tissue/metabolism , Adult , Biomarkers/blood , Body Mass Index , Cholesterol, HDL/blood , Cholesterol, LDL/blood , Female , Humans , Inflammation , Insulin Resistance , Male , Middle Aged , Obesity/diet therapy , Oxidative Stress , Pandemics , SARS-CoV-2 , Triglycerides/blood , Weight Reduction Programs
6.
Nutr Metab Cardiovasc Dis ; 31(9): 2619-2627, 2021 08 26.
Article in English | MEDLINE | ID: covidwho-1349564

ABSTRACT

BACKGROUND AND AIMS: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the sole causative agent of coronavirus infectious disease-19 (COVID-19). METHODS AND RESULTS: We performed a retrospective single-center study of consecutively admitted patients between March 1st and May 15th, 2020, with a definitive diagnosis of SARS-CoV-2 infection. The primary end-point was to evaluate the association of lipid markers with 30-days all-cause mortality in COVID-19. A total of 654 patients were enrolled, with an estimated 30-day mortality of 22.8% (149 patients). Non-survivors had lower total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-c) levels during the entire course of the disease. Both showed a significant inverse correlation with inflammatory markers and a positive correlation with lymphocyte count. In a multivariate analysis, LDL-c ≤ 69 mg/dl (hazard ratio [HR] 1.94; 95% confidence interval [CI] 1.14-3.31), C-reactive protein >88 mg/dl (HR 2.44; 95% CI, 1.41-4.23) and lymphopenia <1000 (HR 2.68; 95% CI, 1.91-3.78) at admission were independently associated with 30-day mortality. This association was maintained 7 days after admission. Survivors presented with complete normalization of their lipid profiles on short-term follow-up. CONCLUSION: Hypolipidemia in SARS-CoV-2 infection may be secondary to an immune-inflammatory response, with complete recovery in survivors. Low LDL-c serum levels are independently associated with higher 30-day mortality in COVID-19 patients.


Subject(s)
COVID-19/blood , Cholesterol, LDL/blood , Dyslipidemias/blood , Aged , Aged, 80 and over , Biomarkers/blood , COVID-19/diagnosis , COVID-19/mortality , COVID-19/therapy , Down-Regulation , Dyslipidemias/diagnosis , Dyslipidemias/mortality , Dyslipidemias/therapy , Female , Humans , Inflammation Mediators/blood , Male , Middle Aged , Prognosis , Retrospective Studies , Risk Assessment , Risk Factors , Spain , Time Factors
7.
Mol Immunol ; 138: 121-127, 2021 10.
Article in English | MEDLINE | ID: covidwho-1347762

ABSTRACT

AIMS: Coronavirus disease 2019 (COVID-19) is a novel viral infection threatening worldwide health as currently there exists no effective treatment strategy and vaccination programs are not publicly available yet. T lymphocytes play an important role in antiviral defenses. However, T cell frequency and functionality may be affected during the disease. MATERIAL AND METHODS: Total blood samples were collected from patients with mild and severe COVID-19, and the total lymphocyte number, as well as CD4+ and CD8 + T cells were assessed using flowcytometry. Besides, the expression of exhausted T cell markers was evaluated. The levels of proinflammatory cytokines were also investigated in the serum of all patients using enzyme-linked immunesorbent assay (ELISA). Finally, the obtained results were analyzed along with laboratory serological reports. RESULTS: COVID-19 patients showed lymphopenia and reduced CD4+ and CD8 + T cells, as well as high percentage of PD-1 expression by T cells, especially in severe cases. Serum secretion of TNF-α, IL-1ß, and IL-2 receptor (IL-2R) were remarkably increased in patients with severe symptoms, as compared with healthy controls. Moreover, high levels of triglyceride (TG) and low density lipoprotein cholesterol (LDL-C), were correlated with the severity of the disease. CONCLUSION: Reduced number and function of T cells were observed in COVID-19 patients, especially in severe patients. Meanwhile, the secretion of proinflammatory cytokines was increased as the disease developed. High level of serum IL-2R was also considered as a sign of lymphopenia. Additionally, hypercholesterolemia and hyperlipidemia could be important prognostic factors in determining the severity of the infection.


Subject(s)
CD4-Positive T-Lymphocytes/immunology , CD8-Positive T-Lymphocytes/immunology , COVID-19/immunology , Lymphopenia/immunology , SARS-CoV-2/immunology , Adult , Aged , CD4-Positive T-Lymphocytes/metabolism , CD4-Positive T-Lymphocytes/virology , CD8-Positive T-Lymphocytes/metabolism , CD8-Positive T-Lymphocytes/virology , COVID-19/metabolism , COVID-19/virology , Cholesterol, LDL/blood , Cytokines/blood , Cytokines/immunology , Cytokines/metabolism , Disease Progression , Female , Humans , Lymphocyte Count , Lymphopenia/blood , Lymphopenia/virology , Male , Middle Aged , Prognosis , SARS-CoV-2/physiology , Severity of Illness Index , Triglycerides/blood
8.
Viruses ; 13(7)2021 07 19.
Article in English | MEDLINE | ID: covidwho-1344395

ABSTRACT

OBJECTIVES: HCV shows complex interactions with lipid metabolism. Our aim was to examine total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) changes in HIV/HCV coinfected patients, after achieving sustained virological response (SVR), according to different HCV genotypes and specific antiretroviral use. METHODS: HIV/HCV coinfected patients, enrolled in the ICONA and HepaICONA cohorts, who achieved DAA-driven SVR were included. Paired t-tests were used to examine whether the pre- and post-SVR laboratory value variations were significantly different from zero. ANCOVA regression models were employed to estimate the causal effect of SVR and of PI/r use on lipid changes. The interaction between the effect of eradication and HCV genotype was formally tested. RESULTS: six hundred and ninety-nine HIV/HCV coinfected patients were enrolled. After HCV eradication, a significant improvement in liver function occurred, with a significant decrease in AST, ALT, GGT, and total plasmatic bilirubin. TC and LDL-C significantly increased by 21.4 mg/dL and 22.4 mg/dL, respectively (p < 0.001), after SVR, whereas there was no evidence for a change in HDL-C (p = 0.45) and triglycerides (p = 0.49). Notably, the TC and LDL-C increase was higher for participants who were receiving darunavir/ritonavir, and the TC showed a more pronounced increase among HCV genotype 3 patients (interaction-p value = 0.002). CONCLUSIONS: complex and rapid changes in TC and LDL-C levels, modulated by HCV genotype and PI/r-based ART combinations, occurred in HIV/HCV coinfected patients after SVR. Further studies are needed to evaluate the clinical impact of these changes on the long-term risk of cardiovascular disease.


Subject(s)
Disease Eradication/statistics & numerical data , HIV Infections/virology , Hepacivirus/genetics , Hepatitis C/prevention & control , Lipid Metabolism , Antiviral Agents/therapeutic use , Cholesterol/blood , Cholesterol, LDL/blood , Cohort Studies , Female , Genotype , Hepacivirus/classification , Hepacivirus/drug effects , Hepatitis C/drug therapy , Humans , Italy , Male , Middle Aged , Sustained Virologic Response
9.
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
10.
Front Endocrinol (Lausanne) ; 12: 611526, 2021.
Article in English | MEDLINE | ID: covidwho-1305635

ABSTRACT

Background: It has been reported that dyslipidemia is related to coronavirus-related diseases. Critical patients with coronavirus disease 2019 (COVID-19) who suffered from multiple organ dysfunctions were treated in the intensive care unit (ICU) in Wuhan, China. Whether the lipids profile was associated with the prognosis of COVID-19 in critical patients remained unclear. Methods: A retrospective study was performed in critical patients (N=48) with coronavirus disease 2019 in Leishenshan hospital between February and April 2020 in Wuhan. The parameters including lipid profiles, liver function, and renal function were collected on admission day, 2-3days after the admission, and the day before the achievement of clinical outcome. Results: Albumin value and creatine kinase (ck) value were statistically decreased at 2-3 days after admission compared with those on admission day (P<0.05). Low density lipoprotein (LDL-c), high density lipoprotein (HDL-c), apolipoprotein A (ApoA), and apolipoprotein A (Apo B) levels were statistically decreased after admission (P<0.05). Logistic regression showed that HDL-c level both on admission day and the day before the achievement of clinical outcome were negatively associated with mortality in critical patients with COVID-19. Total cholesterol (TC) level at 2-3days after admission was related to mortality in critical patients with COVID-19. Conclusions: There were lipid metabolic disorders in the critical patients with COVID-19. Lower levels of HDL-c and TC were related to the progression of critical COVID-19.


Subject(s)
COVID-19/mortality , Dyslipidemias/epidemiology , Hospital Mortality , Multiple Organ Failure/mortality , Aged , Aged, 80 and over , Apolipoproteins A/blood , Apolipoproteins B/blood , COVID-19/blood , COVID-19/epidemiology , China/epidemiology , Cholesterol/blood , Cholesterol, HDL/blood , Cholesterol, LDL/blood , Critical Illness , Dyslipidemias/blood , Female , Humans , Male , Middle Aged , Multiple Organ Failure/blood , Multiple Organ Failure/epidemiology , Retrospective Studies , Risk Factors , SARS-CoV-2 , Severity of Illness Index
11.
Nutrients ; 13(6)2021 Jun 20.
Article in English | MEDLINE | ID: covidwho-1273495

ABSTRACT

Clinical decision support systems (CDSS) are data aggregation tools based on computer technology that assist clinicians to promote healthy weight management and prevention of cardiovascular diseases. We carried out a randomised controlled 3-month trial to implement lifestyle modifications in breast cancer (BC) patients by means of CDSS during the COVID-19 pandemic. In total, 55 BC women at stages I-IIIA were enrolled. They were randomly assigned either to Control group, receiving general lifestyle advice (n = 28) or the CDSS group (n = 27), to whom the CDSS provided personalised dietary plans based on the Mediterranean diet (MD) together with physical activity guidelines. Food data, anthropometry, blood markers and quality of life were evaluated. At 3 months, higher adherence to MD was recorded in the CDSS group, accompanied by lower body weight (kg) and body fat mass percentage compared to control (p < 0.001). In the CDSS arm, global health/quality of life was significantly improved at the trial endpoint (p < 0.05). Fasting blood glucose and lipid levels (i.e., cholesterol, LDL, triacylglycerols) of the CDSS arm remained unchanged (p > 0.05) but were elevated in the control arm at 3 months (p < 0.05). In conclusion, CDSS could be a promising tool to assist BC patients with lifestyle modifications during the COVID-19 pandemic.


Subject(s)
Breast Neoplasms , COVID-19 , Decision Support Systems, Clinical , Diet, Mediterranean , Life Style , Obesity/prevention & control , Pandemics , Adipose Tissue/metabolism , Adult , Behavior Therapy , Blood Glucose/metabolism , Body Mass Index , Body Weight , Cholesterol, LDL/blood , Female , Health Status , Humans , Middle Aged , Obesity/etiology , Patient Compliance , Quality of Life , SARS-CoV-2 , Triglycerides/blood
12.
PLoS One ; 15(11): e0241993, 2020.
Article in English | MEDLINE | ID: covidwho-1218366

ABSTRACT

OBJECTIVES: The aim of this study was to systematically collate and appraise the available evidence regarding the associations between small, dense low-density lipoprotein (sdLDL) and incident coronary heart disease (CHD), focusing on cholesterol concentration (sdLDL-C) and sdLDL particle characteristics (presence, density, and size). BACKGROUND: Coronary heart disease (CHD) is the leading cause of death worldwide. Small, dense low-density lipoprotein (sdLDL) has been hypothesized to induce atherosclerosis and subsequent coronary heart disease (CHD). However, the etiological relevance of lipoprotein particle size (sdLDL) versus cholesterol content (sdLDL-C) remains unclear. METHODS: PubMed, MEDLINE, Web of Science, and EMBASE were systematically searched for studies published before February 2020. CHD associations were based on quartile comparisons in eight studies of sdLDL-C and were based on binary categorization in fourteen studies of sdLDL particle size. Reported hazards ratios (HR) and odds ratios (OR) with 95% confidence interval (CI) were standardized and pooled using a random-effects meta-analysis model. RESULTS: Data were collated from 21 studies with a total of 30,628 subjects and 5,693 incident CHD events. The average age was 67 years, and 53% were men. Higher sdLDL and sdLDL-C levels were both significantly associated with higher risk of CHD. The pooled estimate for the high vs. low categorization of sdLDL was 1.36 (95% CI: 1.21, 1.52) and 1.07 (95% CI: 1.01, 1.12) for comparing the top quartiles versus the bottom of sdLDL-C. Several studies suggested a dose response relationship. CONCLUSIONS: The findings show a positive association between sdLDL or sdLDL-C levels and CHD, which is supported by an increasing body of genetic evidence in favor of its causality as an etiological risk factor. Thus, the results support sdLDL and sdLDL-C as a risk marker, but further research is required to establish sdLDL or sdLDL-C as a potential therapeutic marker for incident CHD risk reduction.


Subject(s)
Cholesterol, LDL/blood , Coronary Disease/blood , Lipoproteins/blood , Atherosclerosis/blood , Atherosclerosis/complications , Biomarkers/analysis , Biomarkers/blood , Cholesterol, LDL/analysis , Coronary Disease/etiology , Humans , Lipoproteins/analysis , Particle Size , Risk Factors
13.
Clin Chim Acta ; 517: 66-73, 2021 Jun.
Article in English | MEDLINE | ID: covidwho-1101131

ABSTRACT

BACKGROUND: We investigated the dynamic changes in lipid profiles and their correlations with disease severity and clinical outcome in patients with severe COVID-19. METHODS: We retrospectively reviewed 519 severe COVID-19 patients with confirmed outcomes (discharged or deceased), admitted to the West Court of Union Hospital in Wuhan, China, between 29 January and 8 April 2020. RESULTS: Altogether, 424 severe COVID-19 patients, including 34 non-survivors and 390 survivors, were included in the final analyses. During hospitalization, low-density lipoprotein cholesterol (LDL-C), total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C) and apolipoprotein A-I (apoA-I) showed an increasing trend in survivors, but showed a downward trend in non-survivors. The serum concentrations of HDL-C and apoA-I were inversely correlated with C-reactive protein (CRP), length of hospital stay of survivors, and disease severity scores. For in-hospital deaths, the areas under the receiver operating characteristic curves (AUCs) of the ratios of CRP/HDL-C and CRP/apoA-I at admission were 0.84 and 0.83, respectively. Moreover, patients with high ratios of CRP/HDL-C (>77.39) or CRP/apoA-I (>72.37) had higher mortality rates during hospitalization (log-rank p < 0.001). Logistic regression analysis demonstrated that hypertension, lactate dehydrogenase, SOFA score, and High CRP/HDL-C ratio were independent predictors of in-hospital mortality. CONCLUSIONS: During severe COVID-19, HDL-C and apoA-I concentrations are dramatically decreased in non-survivors. Moreover, High CRP/HDL-C ratio is significantly associated with an increase in mortality and a poor prognosis.


Subject(s)
COVID-19 , Lipid Metabolism , Aged , Apolipoprotein A-I/blood , C-Reactive Protein/analysis , COVID-19/blood , COVID-19/mortality , COVID-19/physiopathology , China , Cholesterol, HDL/blood , Cholesterol, LDL/blood , Female , Hospitalization , Humans , Male , Middle Aged , Retrospective Studies
16.
Eur Rev Med Pharmacol Sci ; 24(23): 12510-12515, 2020 12.
Article in English | MEDLINE | ID: covidwho-995009

ABSTRACT

OBJECTIVE: Almost all countries announced social restrictions and distancing measures which could unintentionally lead to a decline in admissions to hospital for acute disorders other than signs of pneumonia. We aimed to evaluate lipid profile, neutrophil to lymphocyte ratio (NLR) and cardiovascular admissions to the coronary care unit (CCU) of a tertiary center in Turkey during the COVID-19 era and to compare these results with admissions in the same time interval of the previous year. MATERIALS AND METHODS: We retrospectively analyzed CCU admissions due to new-onset atrial fibrillation, ST-elevation myocardial infarction, non-ST elevation acute coronary syndrome (NSTEACS) and acute heart failure during the COVID-19 outbreak and the same time interval of the past year. Laboratory measurements including lipid profile and NLR values were retrieved from the institutional digital database. RESULTS: Compared to the same time interval of 2019 (March-April, 2019), the number of patients admitted to the CCU with acute cardiovascular disorders (atrial fibrillation, STEMI, NSTEACS and acute heart failure) were lower in the COVID-19 period. The levels of NLR, total cholesterol, and low-density lipoprotein (LDL) cholesterol were significantly higher and high-density lipoprotein (HDL) cholesterol was significantly lower in subjects admitted to the CCU during March-April 2020 compared to subjects admitted in March-April 2019. CONCLUSIONS: Our findings show that subjects admitted to the CCU in the COVID-19 era have an unfavorable lipid profile and elevated NLR compared to those admitted in 2019. These patients appear to be at high risk for future cardiovascular events.


Subject(s)
Acute Coronary Syndrome/blood , Atrial Fibrillation/blood , COVID-19 , Dyslipidemias/blood , Heart Failure/blood , Lymphocyte Count , Neutrophils , ST Elevation Myocardial Infarction/blood , Acute Coronary Syndrome/epidemiology , Aged , Atrial Fibrillation/epidemiology , Cholesterol/blood , Cholesterol, HDL/blood , Cholesterol, LDL/blood , Cohort Studies , Communicable Disease Control , Coronary Care Units , Dyslipidemias/epidemiology , Female , Heart Failure/epidemiology , Humans , Leukocyte Count , Male , Middle Aged , Retrospective Studies , SARS-CoV-2 , ST Elevation Myocardial Infarction/epidemiology , Turkey/epidemiology
17.
PLoS One ; 15(9): e0239573, 2020.
Article in English | MEDLINE | ID: covidwho-793642

ABSTRACT

INTRODUCTION: Severe acute respiratory syndrome coronavirus2 has caused a global pandemic of coronavirus disease 2019 (COVID-19). High-density lipoproteins (HDLs), particles chiefly known for their reverse cholesterol transport function, also display pleiotropic properties, including anti-inflammatory or antioxidant functions. HDLs and low-density lipoproteins (LDLs) can neutralize lipopolysaccharides and increase bacterial clearance. HDL cholesterol (HDL-C) and LDL cholesterol (LDL-C) decrease during bacterial sepsis, and an association has been reported between low lipoprotein levels and poor patient outcomes. The goal of this study was to characterize the lipoprotein profiles of severe ICU patients hospitalized for COVID-19 pneumonia and to assess their changes during bacterial ventilator-associated pneumonia (VAP) superinfection. METHODS: A prospective study was conducted in a university hospital ICU. All consecutive patients admitted for COVID-19 pneumonia were included. Lipoprotein levels were assessed at admission and daily thereafter. The assessed outcomes were survival at 28 days and the incidence of VAP. RESULTS: A total of 48 patients were included. Upon admission, lipoprotein concentrations were low, typically under the reference values ([HDL-C] = 0.7[0.5-0.9] mmol/L; [LDL-C] = 1.8[1.3-2.3] mmol/L). A statistically significant increase in HDL-C and LDL-C over time during the ICU stay was found. There was no relationship between HDL-C and LDL-C concentrations and mortality on day 28 (log-rank p = 0.554 and p = 0.083, respectively). A comparison of alive and dead patients on day 28 did not reveal any differences in HDL-C and LDL-C concentrations over time. Bacterial VAP was frequent (64%). An association was observed between HDL-C and LDL-C concentrations on the day of the first VAP diagnosis and mortality ([HDL-C] = 0.6[0.5-0.9] mmol/L in survivors vs. [HDL-C] = 0.5[0.3-0.6] mmol/L in nonsurvivors, p = 0.036; [LDL-C] = 2.2[1.9-3.0] mmol/L in survivors vs. [LDL-C] = 1.3[0.9-2.0] mmol/L in nonsurvivors, p = 0.006). CONCLUSION: HDL-C and LDL-C concentrations upon ICU admission are low in severe COVID-19 pneumonia patients but are not associated with poor outcomes. However, low lipoprotein concentrations in the case of bacterial superinfection during ICU hospitalization are associated with mortality, which reinforces the potential role of these particles during bacterial sepsis.


Subject(s)
Cholesterol, HDL/blood , Cholesterol, LDL/blood , Coronavirus Infections/blood , Pneumonia, Bacterial/blood , Pneumonia, Ventilator-Associated/blood , Pneumonia, Viral/blood , Superinfection/blood , Aged , Betacoronavirus , COVID-19 , Coronavirus Infections/mortality , Female , France , Hospitals, University , Humans , Intensive Care Units , Male , Middle Aged , Pandemics , Pneumonia, Bacterial/mortality , Pneumonia, Ventilator-Associated/mortality , Pneumonia, Viral/mortality , Prospective Studies , SARS-CoV-2
18.
Lipids Health Dis ; 19(1): 204, 2020 Sep 07.
Article in English | MEDLINE | ID: covidwho-745682

ABSTRACT

BACKGROUND: The purpose of the study is to describe the blood lipid levels of patients diagnosed with coronavirus disease 2019 (COVID-19) and to analyze the correlation between blood lipid levels and the prognosis of COVID-19 patients. METHODS: In the clinical retrospective analysis, a total of 228 adults infected with COVID-19 were enrolled between January 17, 2020 and March 14, 2020, in Changsha, China. One thousand one hundred and forty healthy participants with matched age and gender were used as control. Median with interquartile range and Mann-Whitney test were adopted to describe and analyze clinical data. The Kaplan-Meier (KM) curve and Cox regression analysis were used to analyze the correlation between high-density lipoprotein cholesterol (HDL-C) and the severity of COVID-19. RESULTS: Compared with control, COVID-19 patients showed significantly lower levels of total cholesterol (TC) [median, 3.76 vs 4.65 mmol/L, P = 0.031], triglyceride [median, 1.08 vs 1.21 mmol/L, P <  0.001], low-density lipoprotein cholesterol (LDL-C) [median, 2.63 vs 2.83 mmol/L, P <  0.001], and HDL-C [median, 0.78 vs 1.37 mmol/L, P <  0.001], while compared with non-severe patients, severe COVID-19 patients only presented lower levels of HDL-C [median, 0.69 vs 0.79 mmol/L, P = 0.032]. In comparison with patients with high HDL-C, patients with low HDL-C showed a higher proportion of male (69.57% vs 45.60%, P = 0.004), higher levels of C-reactive protein (CRP) (median, 27.83 vs 12.56 mg/L, P <  0.001) and higher proportion of severe events (36.96% vs 14.84%, P = 0.001). Moreover, patients with low HDL-C at admission showed a higher risk of developing severe events compared with those with high HDL-C (Log Rank P = 0.009). After adjusting for age, gender and underlying diseases, they still had elevated possibility of developing severe cases than those with high HDL-C (HR 2.827, 95% CI 1.190-6.714, P = 0.019). CONCLUSIONS: HDL-C level was lower in COVID-19 adult patients, and low HDL-C in COVID-19 patients was correlated with a higher risk of developing severe events.


Subject(s)
Betacoronavirus , Cholesterol, HDL/blood , Cholesterol, LDL/blood , Coronavirus Infections/physiopathology , Pneumonia, Viral/physiopathology , Adult , C-Reactive Protein/analysis , COVID-19 , China , Cholesterol/blood , Coronavirus Infections/blood , Female , Humans , Male , Middle Aged , Pandemics , Pneumonia, Viral/blood , Retrospective Studies , Risk Factors , SARS-CoV-2 , Severity of Illness Index , Sex Factors , Triglycerides/blood
19.
Sci China Life Sci ; 63(11): 1678-1687, 2020 11.
Article in English | MEDLINE | ID: covidwho-610883

ABSTRACT

Coronavirus disease 2019 (COVID-19) is a global pandemic which has caused numerous deaths worldwide. The present study investigated the roles of hypoproteinemia in the clinical outcome and liver dysfunction of COVID-19 patients. In this retrospective study, we extracted data from 2,623 clinically confirmed adult COVID-19 patients (>18 years old) between January 29, 2020 and March 6, 2020 in Tongji Hospital, Wuhan, China. The patients were divided into three groups-non-critically ill, critically ill, and death groups-in accordance with the Chinese Clinical Guideline for COVID-19. Serum albumin, low-density lipoproteins cholesterol (LDL-C), and high-density lipoproteins cholesterol (HDL-C) concentrations and inflammatory cytokines levels were measured and compared among these three groups. The median age of these 2,623 patients was 64 years old (interquartile range (IQR), 52-71). Among the patients enrolled in the study, 2,008 (76.6%) were diagnosed as non-critically ill and 615 (23.4%) were critically ill patients, including 383 (14.6%) critically ill survivors and 232 (8.8%) critically ill deaths in the hospital. Marked hypoalbuminemia occurred in 38.2%, 71.2%, and 82.4% patients in non-critically ill, critically ill, and death groups, respectively, on admission and 45.9%, 77.7%, and 95.6% of these three groups, respectively, during hospitalization. We also discovered that serum low-density lipoprotein (LDL) and HDL levels were significantly lower in critically ill and death groups compared to non-critically ill group. Meanwhile, the patients displayed dramatically elevated levels of serum inflammatory factors, while a markedly prolonged activated partial thromboplastin time (APTT) in critically ill patients reflected coagulopathy. This study suggests that COVID-19-induced cytokine storm causes hepatotoxicity and subsequently critical hypoalbuminemia, which are associated with exacerbation of disease-associated inflammatory responses and progression of the disease and ultimately leads to death for some critically ill patients.


Subject(s)
COVID-19/blood , COVID-19/complications , Coronavirus Infections/blood , Coronavirus Infections/complications , Liver Diseases/etiology , Serum Albumin, Human/metabolism , Aged , COVID-19/mortality , China , Cholesterol, HDL/blood , Cholesterol, LDL/blood , Coronavirus Infections/mortality , Critical Illness , Cytokines/blood , Female , Humans , Liver Diseases/blood , Male , Middle Aged , Prognosis , Retrospective Studies , Risk Factors , SARS-CoV-2 , Thromboplastin/metabolism , Time Factors
20.
Metabolism ; 107: 154243, 2020 06.
Article in English | MEDLINE | ID: covidwho-602136

ABSTRACT

BACKGROUND: The pandemic of coronavirus disease 2019 (COVID-19) has become a global threat to public health. The lipid pathophysiology in COVID-19 is unknown. METHODS: In this retrospective longitudinal study, we monitored the serum lipids in 17 surviving and 4 non-surviving COVID-19 cases prior to their viral infections and duration the entire disease courses. RESULTS: In surviving cases, the low-density lipoprotein (LDL) levels decreased significantly on admission as compared with the levels before infection; the LDL levels remained constantly low during the disease progression and resumed to the original levels when patients recovered (pre-infection: 3.5 (3.0-4.4); on admission: 2.8 (2.3-3.1), p < 0.01; progression: 2.5 (2.3-3.0); discharge: 3.6 (2.7-4.1); median (IQR), in mmol/L). In non-surviving patients, LDL levels showed an irreversible and continuous decrease until death (1.1 (0.9-1.2), p = 0.02 versus the levels on admission). The ratio changes of LDL levels inversely correlated with ratio changes of high-sensitivity C-reactive protein levels. Logistic regression analysis showed increasing odds of lowered LDL levels associated with disease progression (odds ratio: 4.48, 95% IC: 1.55-12.92, p = 0.006) and in-hospital death (odds ratio: 21.72, 95% IC: 1.40-337.54, p = 0.028). CONCLUSIONS: LDL levels inversely correlated to disease severities, which could be a predictor for disease progress and poor prognosis.


Subject(s)
Cholesterol, LDL/blood , Coronavirus Infections/blood , Coronavirus Infections/diagnosis , Pneumonia, Viral/blood , Pneumonia, Viral/diagnosis , Aged , Betacoronavirus , C-Reactive Protein/analysis , COVID-19 , China , Comorbidity , Disease Progression , Female , Humans , Longitudinal Studies , Male , Middle Aged , Pandemics , Prognosis , Retrospective Studies , SARS-CoV-2
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