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.).

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.

HDL proteome remodeling associates with COVID-19 severity.

BACKGROUND: Besides the well-accepted role in lipid metabolism, high-density lipoprotein (HDL) also seems to participate in host immune response against infectious diseases. OBJECTIVE: We used a quantitative proteomic approach to test the hypothesis that alterations in HDL proteome associate with severity of Coronavirus disease 2019 (COVID-19). METHODS: Based on clinical criteria, subjects (n=41) diagnosed with COVID-19 were divided into two groups: a group of subjects presenting mild symptoms and a second group displaying severe symptoms and requiring hospitalization. Using a proteomic approach, we quantified the levels of 29 proteins in HDL particles derived from these subjects. RESULTS: We showed that the levels of serum amyloid A 1 and 2 (SAA1 and SAA2, respectively), pulmonary surfactant-associated protein B (SFTPB), apolipoprotein F (APOF), and inter-alpha-trypsin inhibitor heavy chain H4 (ITIH4) were increased by more than 50% in hospitalized patients, independently of sex, HDL-C or triglycerides when comparing with subjects presenting only mild symptoms. Altered HDL proteins were able to classify COVID-19 subjects according to the severity of the disease (error rate 4.9%). Moreover, apolipoprotein M (APOM) in HDL was inversely associated with odds of death due to COVID-19 complications (odds ratio [OR] per 1-SD increase in APOM was 0.27, with 95% confidence interval [CI] of 0.07 to 0.72, P=0.007). CONCLUSION: Our results point to a profound inflammatory remodeling of HDL proteome tracking with severity of COVID-19 infection. They also raise the possibility that HDL particles could play an important role in infectious diseases.

Uneven metabolic and lipidomic profiles in recovered COVID-19 patients as investigated by plasma NMR metabolomics.

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.

Prognostic Value of Leucocyte to High-Density Lipoprotein-Cholesterol Ratios in COVID-19 Patients and the Diabetes Subgroup.

Background: Blood parameters, such as neutrophil-to-lymphocyte ratio, have been identified as reliable inflammatory markers with diagnostic and predictive value for the coronavirus disease 2019 (COVID-19). However, novel hematological parameters derived from high-density lipoprotein-cholesterol (HDL-C) have rarely been studied as indicators for the risk of poor outcomes in patients with severe acute respiratory syndrome-related coronavirus 2 (SARS-CoV-2) infection. Here, we aimed to assess the prognostic value of these novel biomarkers in COVID-19 patients and the diabetes subgroup. Methods: We conducted a multicenter retrospective cohort study involving all hospitalized patients with COVID-19 from January to March 2020 in five hospitals in Wuhan, China. Demographics, clinical and laboratory findings, and outcomes were recorded. Neutrophil to HDL-C ratio (NHR), monocyte to HDL-C ratio (MHR), lymphocyte to HDL-C ratio (LHR), and platelet to HDL-C ratio (PHR) were investigated and compared in both the overall population and the subgroup with diabetes. The associations between blood parameters at admission with primary composite end-point events (including mechanical ventilation, admission to the intensive care unit, or death) were analyzed using Cox proportional hazards regression models. Receiver operating characteristic curves were used to compare the utility of different blood parameters. Results: Of 440 patients with COVID-19, 67 (15.2%) were critically ill. On admission, HDL-C concentration was decreased while NHR was high in patients with critical compared with non-critical COVID-19, and were independently associated with poor outcome as continuous variables in the overall population (HR: 0.213, 95% CI 0.090-0.507; HR: 1.066, 95% CI 1.030-1.103, respectively) after adjusting for confounding factors. Additionally, when HDL-C and NHR were examined as categorical variables, the HRs and 95% CIs for tertile 3 vs. tertile 1 were 0.280 (0.128-0.612) and 4.458 (1.817-10.938), respectively. Similar results were observed in the diabetes subgroup. ROC curves showed that the NHR had good performance in predicting worse outcomes. The cutoff point of the NHR was 5.50. However, the data in our present study could not confirm the possible predictive effect of LHR, MHR, and PHR on COVID-19 severity. Conclusion: Lower HDL-C concentrations and higher NHR at admission were observed in patients with critical COVID-19 than in those with noncritical COVID-19, and were significantly associated with a poor prognosis in COVID-19 patients as well as in the diabetes subgroup.

Causal Associations Between Blood Lipids and COVID-19 Risk: A Two-Sample Mendelian Randomization Study.

[Figure: see text].

The association of metabolic syndrome and COVID-19 deterioration.

BACKGROUND AND AIMS: To evaluate the prevalence and prognostic value of metabolic syndrome (MetS) in patients admitted for coronavirus disease 2019 (COVID-19). METHODS AND RESULTS: In this monocentric cohort retrospective study, we consecutively included all adult patients admitted to COVID-19 units between April 9 and May 29, 2020 and between February 1 and March 26, 2021. MetS was defined when at least three of the following components were met: android obesity, high HbA1c, hypertension, hypertriglyceridemia, and low HDL cholesterol. COVID-19 deterioration was defined as the need for nasal oxygen flow ≥6 L/min within 28 days after admission. We included 155 patients (55.5% men, mean age 61.7 years old, mean body mass index 29.8 kg/m2). Fifty-six patients (36.1%) had COVID-19 deterioration. MetS was present in 126 patients (81.3%) and was associated with COVID-19 deterioration (no-MetS vs MetS: 13.7% and 41.2%, respectively, p < 0.01). Logistic regression taking into account MetS, age, gender, ethnicity, period of inclusion, and Charlson Index showed that COVID-19 deterioration was 5.3 times more likely in MetS patients (95% confidence interval 1.3-20.2) than no-MetS patients. CONCLUSIONS: Over 81.3% of patients hospitalized in COVID-19 units had MetS. This syndrome appears to be an independent risk factor of COVID-19 deterioration.

Integrated Safety Analysis of Abrocitinib for the Treatment of Moderate-to-Severe Atopic Dermatitis From the Phase II and Phase III Clinical Trial Program.

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.

Temporal changes in soluble angiotensin-converting enzyme 2 associated with metabolic health, body composition, and proteome dynamics during a weight loss diet intervention: a randomized trial with implications for the COVID-19 pandemic.

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.

Low serum level of apolipoprotein A1 may predict the severity of COVID-19: A retrospective study.

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.

Dyslipidemia Is Related to Mortality in Critical Patients With Coronavirus Disease 2019: A Retrospective Study.

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.

High triglyceride to HDL-cholesterol ratio as a biochemical marker of severe outcomes in COVID-19 patients.

BACKGROUND & AIMS: Coronavirus disease 2019 (COVID-19) patients with severe complications have shown comorbidities with cardiovascular-disease, hypertension and type 2 diabetes mellitus; clinical disorders that share the common metabolic alterations of insulin resistance and dyslipidaemia. A high triglyceride to high density lipoprotein cholesterol (Tg/HDL c) ratio has been associated with reduced insulin sensitivity, metabolic syndrome and adverse cardiovascular events. Our aim in this study was to determine the association between different components of the lipid profile and particularly the Tg/HDL c ratio with severe complications like the requirement of invasive mechanical ventilation in COVID-19 patients. METHODS: We collected demographic, clinical and biochemical data to conduct a cohort study in 43 adult patients with confirmed COVID-19 diagnosis by quantitative polymerase chain reaction (qPCR) at baseline and in the subsequent 15 days. Patients were subjected to a very similar treatment scheme with the JAK1/2 inhibitor ruxolitinib. Descriptive statistics, variable association and logistic regression were applied to identify predictors of disease severity among elements and calculations from the lipid profile. RESULTS: Patients were aged 57 ± 14 years; 55.8% were male from which 75% required hospitalization and 44.2% were female who 58% were hospitalized. The most common comorbidities were type 2 diabetes mellitus (58%) and hypertension (40%). Hospitalized and critical care patients showed lower HDL c blood levels and increased Tg/HDL c ratio than those with outpatient management and mild/asymptomatic COVID-19. Tg/HDL c ratio correlated with variables of disease severity such as lactate dehydrogenase (LDH) levels (r = 0.356; p < 0.05); National Early Warning Score 2 (NEWS 2) (r = 0.495; p < 0.01); quick sequential organ failure assessment (qSOFA) (r = 0.538; p < 0.001); increased need of oxygen support (r = 0.447; p < 0.01) and requirement of mechanical ventilation (r = 0.378; p < 0.05). Tg/HDL c ratio had a negative correlation with partial oxygen saturation/fraction of inspired oxygen (SaO 2/FiO2) ratio (r = -0.332;p < 0.05). Linear regression analysis showed that Tg/HDL c ratio can predict increases in inflammatory factors like LDH (p < 0.01); ferritin (p < 0.01) and D-dimer (p < 0.001). Logistic regression model indicated that ≥7.45 Tg/HDL c ratio predicts requirement of invasive mechanical ventilation (OR 11.815, CI 1.832-76.186, p < 0.01). CONCLUSIONS: The Tg/HDLc ratio can be used as an early biochemical marker of COVID-19 severe prognosis with requirement of invasive mechanical ventilation.

High plasma concentration of non-esterified polyunsaturated fatty acids is a specific feature of severe COVID-19 pneumonia.

COVID-19 pneumonia has specific features and outcomes that suggests a unique immunopathogenesis. Severe forms of COVID-19 appear to be more frequent in obese patients, but an association with metabolic disorders is not established. Here, we focused on lipoprotein metabolism in patients hospitalized for severe pneumonia, depending on COVID-19 status. Thirty-four non-COVID-19 and 27 COVID-19 patients with severe pneumonia were enrolled. Most of them required intensive care. Plasma lipid levels, lipoprotein metabolism, and clinical and biological (including plasma cytokines) features were assessed. Despite similar initial metabolic comorbidities and respiratory severity, COVID-19 patients displayed a lower acute phase response but higher plasmatic concentrations of non-esterified fatty acids (NEFAs). NEFA profiling was characterised by higher level of polyunsaturated NEFAs (mainly linoleic and arachidonic acids) in COVID-19 patients. Multivariable analysis showed that among severe pneumonia, COVID-19-associated pneumonia was associated with higher NEFAs, lower apolipoprotein E and lower high-density lipoprotein cholesterol concentrations, independently of body mass index, sequential organ failure (SOFA) score, and C-reactive protein levels. NEFAs and PUFAs concentrations were negatively correlated with the number of ventilator-free days. Among hospitalized patients with severe pneumonia, COVID-19 is independently associated with higher NEFAs (mainly linoleic and arachidonic acids) and lower apolipoprotein E and HDL concentrations. These features might act as mediators in COVID-19 pathogenesis and emerge as new therapeutic targets. Further investigations are required to define the role of NEFAs in the pathogenesis and the dysregulated immune response associated with COVID-19.Trial registration: NCT04435223.

Low HDL and high triglycerides predict COVID-19 severity.

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.

Association of serum HDL-cholesterol and apolipoprotein A1 levels with risk of severe SARS-CoV-2 infection.

Individuals with features of metabolic syndrome are particularly susceptible to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), a novel coronavirus associated with the severe respiratory disease, coronavirus disease 2019 (COVID-19). Despite considerable attention dedicated to COVID-19, the link between metabolic syndrome and SARS-CoV-2 infection remains unclear. Using data from the UK Biobank, we investigated the relationship between severity of COVID-19 and metabolic syndrome-related serum biomarkers measured prior to SARS-CoV-2 infection. Logistic regression analyses were used to test biomarker levels and biomarker-associated genetic variants with SARS-CoV-2-related outcomes. Among SARS-CoV-2-positive cases and negative controls, a 10 mg/dl increase in serum HDL-cholesterol or apolipoprotein A1 levels was associated with ∼10% reduced risk of SARS-CoV-2 infection, after adjustment for age, sex, obesity, hypertension, type 2 diabetes, and coronary artery disease. Evaluation of known genetic variants for HDL-cholesterol revealed that individuals homozygous for apolipoprotein E4 alleles had ∼2- to 3-fold higher risk of SARS-CoV-2 infection or mortality from COVID-19 compared with apolipoprotein E3 homozygotes, even after adjustment for HDL-cholesterol levels. However, cumulative effects of all evaluated HDL-cholesterol-raising alleles and Mendelian randomization analyses did not reveal association of genetically higher HDL-cholesterol levels with decreased risk of SARS-CoV-2 infection. These results implicate serum HDL-cholesterol and apolipoprotein A1 levels measured prior to SAR-CoV-2 exposure as clinical risk factors for severe COVID-19 infection but do not provide evidence that genetically elevated HDL-cholesterol levels are associated with SAR-CoV-2 infection.

Lipid metabolism changes in patients with severe COVID-19.

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.

The clinical value of high-density lipoprotein in the evaluation of new coronavirus pneumonia.

BACKGROUND: The new coronavirus pneumonia (NCP, COVID-19) outbreak began in Wuhan in December 2019. The new coronavirus (2019 novel coronavirus (2019-nCoV)) can cause multiple organ damage, mainly to lung tissue, and induce inflammation in the body. OBJECTIVES: To investigate the changes of high-density lipoprotein (HDL) level in patients with COVID-19 and assess its value in the evaluation and prognosis of this disease. MATERIAL AND METHODS: This paper is a cross-sectional retrospective study. Eighty-six severe COVID-19 patients, 132 non-severe COVID-19 patients and 76 healthy individuals (control group) were recruited to measure triglyceride (TG), total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), and low-density lipoprotein cholesterol (LDL-C) using enzyme-coupled colorimetry. RESULTS: The serum HDL-C level in COVID-19 group was 1.02 ±0.28 mmol/L which was significantly lower than in control group (1.52 ±0.55 mmol/L) (p < 0.05). In addition, the serum HDL-C level in severe COVID-19 group was 0.83 ±1.67 mmol/L, which was significantly lower than that in non-severe COVID-19 group (1.15 ±0.27 mmol/L) (p < 0.05). CONCLUSIONS: Changes in HDL levels in patients with COVID-19 can reflect the severity of the disease and have a clinical significance in establishing the prognosis.

Containment measures established during the COVID-19 outbreak and its impact on lipid profile and neutrophil to lymphocyte ratio.

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.

High-density lipoprotein cholesterol as a factor affecting virus clearance in covid-19 patients.

OBJECTIVE: There were COVID-19 patients with SARS-COV-2 nucleic acid long-term positive. This article aims to understand the relevant factors that affect SARS-COV-2 clearance time. METHODS: The clinical data of 115 COVID-19 patients with SARS-COV-2 nucleic acid positive time exceeding 14 days were collected retrospectively, and the relationship between clinical characteristics, chest CT scans, blood cells, biochemical indicators, and the time of viral nucleic acid turning negative were analyzed. RESULTS: The time from symptom onsets to nucleic acid turning negative was (32.5 ± 8.7) days in this group of patients. The time of nucleic acid turning negative: no fever group was longer than fever group, diabetes group was longer than no comorbidity group, elevated levels of ALT (alanine aminotransferase), or GLU (fasting blood glucose) group, decreased levels of ALB (albumin) group or HDLC (high-density lipoprotein cholesterol) group was longer than it's normal group separately (P < 0.05). Cox multivariate regression analysis showed that ALT [odds ratio (OR): 2.164 (95% CI: 1.276-3.670), P = 0.004], GLU [OR: 2.064 (95% CI: 1.195-3.566), P = 0.009] and HDLC [OR: 0.527 (95% CI: 0.307-0.907), P = 0.021] were independent factors which affected the time of nucleic acid turning negative. CONCLUSIONS: ALT, GLU and HDLC were independent factors that influenced the time of nucleic acid turning negative. Although diabetes or hyperglycemia is a known risk factor, HDLC is the first to be identified, clinicians should be aware of dyslipidemia in covid-19 patients.