Assessment of Serum Lipocalin-2 Level as Early Predictor Marker to Severe COVID-19 Disease

The coronavirus disease of 2019 (COVID-19) is an emerging coronavirus that affects people's respiratory systems (Severe acute respiratory syndrome coronavirus) and can the rapidly growing COVID-19 pandemic represents a significant global challenge, It can be considered that lipocalin-2 was highly associated with the severity of COVID-19. Therefore, it may be a useful biomarker for diagnosing disease severity in COVID-19 patients. lipocalin-2 was initially identified as a secreted protein from human neutrophils. Alveolar type II cells that have been damaged primarily express this substance. To verify lipocalin-2's potential as a diagnosing biomarker for COVID-19 patients, Lipocalin-2 levels in the blood were examined in this pilot investigation. To examine the relationship between serum lipocalin-2 levels and the severity of COVID-19 infection to see if this protein may be utilized as a disease indicator. This study was done in a case-control study with One hundred and twenty patients (79 males, 41 females) with COVID-19 who participated in the research. The COVID-19 patients were divided into three groups based on the severity of the illness: critical disease (n = 30), severe disease (n = 30), and mild/moderate disease (n = 60), with (n = 60) healthy volunteers serving as the control group (35 males, 25 females). Between January 2022 and May 2022, the patients were obtained from Al-Amal hospitals and the AL-Shefaa centre in ALNajaf City, Iraq., All of the patients' fundamental clinical and demographic data were collected along with blood samples. Enzyme-linked immunosorbent tests were used to measure the blood's level of LCN2 (ELISA). The levels of total cholesterol, triglycerides, and High-Density lipoprotein were assessed using colorimetric methods. Ichroma was tested for serum ferritin, D-dimer, and CBC by Swelab. ran a statistical study to see if they were related to the severity of the disease. Higher lipocalin-2 levels were observed in the patient group, particularly in cases of mild/moderate (1.32±0.30) (P. 0.001), severe(2.16±0.42) (P. 0.001), and critical(4.71±1.01) (P. 0.001) comparing cases to healthy controls (0.86±0.51) respectively, groupings. (SPO2 %, Hb, TC, HDL, LDL, and lymphocyte) levels were found to significant negative correlation with one another in the COVID-19 patient group, with p-values=0.001 for each of these relationships. Moreover, a significant positive correlation between (TG, VLDL-C, WBCs, neutrophil, platelet, N/L ratio, D-dimer, Ferritin, and CRP, p.value=0.001 for each one of them) levels with lipocalin-2 in the COVID-19 patients group. a cut-off value of 1.215 (ng/mL) for lipocalin-2 predicted severe COVID-19 with a sensitivity of 81.7 % and a specificity of 80.2 % (AUC: 0.9, 95%CI 0.852-0.949;p<0.0001). [ FROM AUTHOR] Copyright of Egyptian Academic Journal of Biological Sciences, C Physiology & Molecular Biology is the property of Egyptian Academic Journal of Biological Sciences and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full . (Copyright applies to all s.)

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

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

Aminothiols exchange in coronavirus disease 2019

Clinical manifestation of the inflammatory process in its relation to biochemical markers (total cysteine [Cys], cysteine-glycine [CysGly], glutathione [GSH], glutamate-cysteine [Glu-Cys], homocysteine [Hcy], the ratio of reduced to oxidized glutathione [GSH/GSSG], the ratio of reduced to oxidized cysteine [CySH/CySS], malondialdehyde-oxidized low-density lipoproteins [MDA-oxLDL]) has been studied in patients with coronavirus disease 2019 (COVID-19). 48 patients with mild to severe COVID-19 and 20 healthy volunteers were included in our research. The participants were divided into 4 experimental groups according to inflammation intensity estimated based on the serum levels of interleukin 6 (IL-6). All 4 groups showed the prevalence of male patients and elevated serum levels of IL-6 (by 54.6%). There was no comorbidity in patients with mild COVID-19 (nasopharyngitis symptoms) and in healthy control subjects. 50% of patients with lung damage had accompanying diseases. Alterations of aminoethyl metabolism were detected in COVID-19 patients: as reflected by the decreased levels of Cys, CysGly, and Glu-Cys and the increased levels of GSH as compared to the control group. Elevation of IL-6 over 7.5 pg/mL was associated with decreased GSH/GSSG and CySH/CySS ratios indicating enhanced oxidative stress and was followed by protein oxidation, specifically MDA-oxLDL. [ FROM AUTHOR]

Atherosclerosis, Cardiovascular Disorders and COVID-19: Comorbid Pathogenesis.

The article describes how atherosclerosis and coronavirus disease 19 (COVID-19) may affect each other. The features of this comorbid pathogenesis at various levels (vascular, cellular and molecular) are considered. A bidirectional influence of these conditions is described: the presence of cardiovascular diseases affects different individuals' susceptibility to viral infection. In turn, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can have a negative effect on the endothelium and cardiomyocytes, causing blood clotting, secretion of pro-inflammatory cytokines, and thus exacerbating the development of atherosclerosis. In addition to the established entry into cells via angiotensin-converting enzyme 2 (ACE2), other mechanisms of SARS-CoV-2 entry are currently under investigation, for example, through CD147. Pathogenesis of comorbidity can be determined by the influence of the virus on various links which are meaningful for atherogenesis: generation of oxidized forms of low-density lipoproteins (LDL), launch of a cytokine storm, damage to the endothelial glycocalyx, and mitochondrial injury. The transformation of a stable plaque into an unstable one plays an important role in the pathogenesis of atherosclerosis complications and can be triggered by COVID-19. The impact of SARS-CoV-2 on large vessels such as the aorta is more complex than previously thought considering its impact on vasa vasorum. Current information on the mutual influence of the medicines used in the treatment of atherosclerosis and acute COVID-19 is briefly summarized.

Evaluation of Tau, amyloid beta, dynorphin levels and number of biochemical variables in covid-19 patients

The study aimed to determine the levels of Tau, amyloid beta, dynorphin, and number of biochemical variables in men with COVID-19. The study groups included 30 men with COVID-19, 30 men who recovered from COVID -19, and 30 healthy men as a control group. Protein and biochemical assays include: tau, amyloid beta, dynorphin, zinc, triglycerides, HDL-C, VLDL-C and cholesterol. The results were a significant increase (P 0.05) in the levels of amyloid beta, dynorphin, HDL-C, cholesterol and LDL-C in patients. Those infected with COVID-19 compared to the control group, while in the recovery group, amyloid beta was low compared to the control group, while zinc and lipid profile were high in the recovered. While tau protein, zinc, triglycerides and VLDL-C showed a significant decrease at (P< 0.05) in the affected men group compared to the control group.

Quantitative Serum NMR Spectroscopy Stratifies COVID-19 Patients and Sheds Light on Interfaces of Host Metabolism and the Immune Response with Cytokines and Clinical Parameters.

The complex manifestations of COVID-19 are still not fully decoded on the molecular level. We combined quantitative the nuclear magnetic resonance (NMR) spectroscopy serum analysis of metabolites, lipoproteins and inflammation markers with clinical parameters and a targeted cytokine panel to characterize COVID-19 in a large (534 patient samples, 305 controls) outpatient cohort of recently tested PCR-positive patients. The COVID-19 cohort consisted of patients who were predominantly in the initial phase of the disease and mostly exhibited a milder disease course. Concerning the metabolic profiles of SARS-CoV-2-infected patients, we identified markers of oxidative stress and a severe dysregulation of energy metabolism. NMR markers, such as phenylalanine, inflammatory glycoproteins (Glyc) and their ratio with the previously reported supramolecular phospholipid composite (Glyc/SPC), showed a predictive power comparable to laboratory parameters such as C-reactive protein (CRP) or ferritin. We demonstrated interfaces between the metabolism and the immune system, e.g., we could trace an interleukin (IL-6)-induced transformation of a high-density lipoprotein (HDL) to a pro-inflammatory actor. Finally, we showed that metadata such as age, sex and constitution (e.g., body mass index, BMI) need to be considered when exploring new biomarkers and that adding NMR parameters to existing diagnoses expands the diagnostic toolbox for patient stratification and personalized medicine.

Dyslipidemia and Inflammation as Hallmarks of Oxidative Stress in COVID-19: A Follow-Up Study.

Recent works have demonstrated a significant reduction in cholesterol levels and increased oxidative stress in patients with coronavirus disease 2019 (COVID-19). The cause of this alteration is not well known. This study aimed to comprehensively evaluate their possible association during the evolution of COVID-19. This is an observational prospective study. The primary endpoint was to analyze the association between lipid peroxidation, lipid, and inflammatory profiles in COVID-19 patients. A multivariate regression analysis was employed. The secondary endpoint included the long-term follow-up of lipid profiles. COVID-19 patients presented significantly lower values in their lipid profile (total, low, and high-density lipoprotein cholesterol) with greater oxidative stress and inflammatory response compared to the healthy controls. Lipid peroxidation was the unique oxidative parameter with a significant association with the total cholesterol (OR: 0.982; 95% CI: 0.969-0.996; p = 0.012), IL1-RA (OR: 0.999; 95% CI: 0.998-0.999; p = 0.021) IL-6 (OR: 1.062; 95% CI: 1.017-1.110; p = 0.007), IL-7 (OR: 0.653; 95% CI: 0.433-0.986; p = 0.042) and IL-17 (OR: 1.098; 95% CI: 1.010-1.193; p = 0.028). Lipid abnormalities recovered after the initial insult during long-term follow-up (IQR 514 days); however, those with high LPO levels at hospital admission had, during long-term follow-up, an atherogenic lipid profile. Our study suggests that oxidative stress in COVID-19 is associated with derangements of the lipid profile and inflammation. Survivors experienced a recovery in their lipid profiles during long-term follow-up, but those with stronger oxidative responses had an atherogenic lipid profile.

An Old Mobbing Story and Covid-19

Innovative medical education greatly relies on lifelong learning with universal standards in research, for generating novel knowledge for improvement maximum patient care. The other side of innovative medical education relies on success of development of novel ideas, perspective;skill building, future career objectives. Leaders have curious roles in the research assistant education. In the current century, both technology and education raced forward in many countries. Mobbing and bullying is an important problem in all fields, every sphere of life in workplaces. Unethical behavior must not take place in universities because universities are the centers of learning, and best academic teaching in ethical standards. Bullying may damage every individual in every academic degree and effect academic performance. In this paper I will discuss a mobbing case which is done to a young academician in many years ago, which is not most frequently observed type. However, such bullying behaviors may increase due to COVID-19 pandemic. Because COVID-19 pandemic may cause various problems in social groups difficulties, anxiety, and economic challenges, problems. Nowadays everybody is experiencing worry, uncertainty, anxiety, fear of economic problems, fear of dying. COVID-19 pandemic has created some unexpected problems to everybody however, academic researchers have additional worries and fears such as;the expiration time of chemicals, problems on chemicals are not imported from abroad on time also difficulties of knockout or transgenic experimental animals cannot be imported from abroad on time, and all these problems cause fear of unsuccessful experimental results, spending extra time. All these anxieties may cause arouse increasing unstable friendships and mobbing possibilities. The COVID-19 disease takes our future and experimental plans to waste basket and change everything including friendship.

The Influence of SARS-CoV-2 Infection on Lipid Metabolism-The Potential Use of Lipid-Lowering Agents in COVID-19 Management.

Several studies have indicated lipid metabolism alterations during COVID-19 infection, specifically a decrease in high-density lipoprotein (HDL) and low-density lipoprotein (LDL) concentrations and an increase in triglyceride (TG) levels during the infection. However, a decline in triglycerides can also be observed in critical cases. A direct correlation can be observed between a decrease in serum cholesterol, HDL-C, LDL-C and TGs, and the severity of the disease; these laboratory findings can serve as potential markers for patient outcomes. The transmission of coronavirus increases proportionally with rising levels of cholesterol in the cell membrane. This is due to the fact that cholesterol increases the number of viral entry spots and the concentration of angiotensin-converting enzyme 2 (ACE2) receptor, crucial for viral penetration. Studies have found that lower HDL-C levels correspond with a higher susceptibility to SARS-CoV-2 infection and infections in general, while higher HDL-C levels were related to a lower risk of developing them. However, extremely high HDL-C levels in serum increase the risk of infectious diseases and is associated with a higher risk of cardiovascular events. Low HDL-C levels are already accepted as a marker for risk stratification in critical illnesses, and higher HDL-C levels prior to the infection is associated with a lower risk of death in older patients. The correlation between LDL-C levels and disease severity is still unclear. However, TG levels were significantly higher in non-surviving severe patients compared to those that survived; therefore, elevated TG-C levels in COVID-19 patients may be considered an indicator of uncontrolled inflammation and an increased risk of death.

Anti-Inflammatory Activity of CIGB-258 against Acute Toxicity of Carboxymethyllysine in Paralyzed Zebrafish via Enhancement of High-Density Lipoproteins Stability and Functionality.

Background: Hyperinflammation is frequently associated with the chronic pain of autoimmune disease and the acute death of coronavirus disease (COVID-19) via a severe cytokine cascade. CIGB-258 (Jusvinza®), an altered peptide ligand with 3 kDa from heat shock protein 60 (HSP60), inhibits the systemic inflammation and cytokine storm, but the precise mechanism is still unknown. Objective: The protective effect of CIGB-258 against inflammatory stress of N-ε-carboxymethyllysine (CML) was tested to provide mechanistic insight. Methods: CIGB-258 was treated to high-density lipoproteins (HDL) and injected into zebrafish and its embryo to test a putative anti-inflammatory activity under presence of CML. Results: Treatment of CML (final 200 µM) caused remarkable glycation of HDL with severe aggregation of HDL particles to produce dysfunctional HDL, which is associated with a decrease in apolipoprotein A-I stability and lowered paraoxonase activity. Degradation of HDL3 by ferrous ions was attenuated by a co-treatment with CIGB-258 with a red-shift of the Trp fluorescence in HDL. A microinjection of CML (500 ng) into zebrafish embryos resulted in the highest embryo death rate, only 18% of survivability with developmental defects. However, co-injection of CIGB-258 (final 1 ng) caused the remarkable elevation of survivability around 58%, as well as normal developmental speed. An intraperitoneal injection of CML (final 250 µg) into adult zebrafish resulted acute paralysis, sudden death, and laying down on the bottom of the cage with no swimming ability via neurotoxicity and inflammation. However, a co-injection of CIGB-258 (1 µg) resulted in faster recovery of the swimming ability and higher survivability than CML alone injection. The CML alone group showed 49% survivability, while the CIGB-258 group showed 97% survivability (p < 0.001) with a remarkable decrease in hepatic inflammation up to 50%. A comparison of efficacy with CIGB-258, Infliximab (Remsima®), and Tocilizumab (Actemra®) showed that the CIGB-258 group exhibited faster recovery and swimming ability with higher survivability than those of the Infliximab group. The CIGB-258 group and Tocilizumab group showed the highest survivability, the lowest plasma total cholesterol and triglyceride level, and the infiltration of inflammatory cells, such as neutrophils in hepatic tissue. Conclusion: CIGB-258 ameliorated the acute neurotoxicity, paralysis, hyperinflammation, and death induced by CML, resulting in higher survivability in zebrafish and its embryos by enhancing the HDL structure and functionality.

Significant Worsening of Preexisting Obesity in South Texas Children during COVID-19 Lockdown

Background: Obesity has been on the rise for the past several decades, which is associated with increased risk for comorbidities and severe consequences to the individual. In the Mexican American community, obesity has become a serious problem in children. The COVID-19 lockdown order issued in February 2020 caused further challenges for children to engage in regular physical activity. Objective: To determine if the COVID-19 lockdown impacted the weight of 95% Medicaid-insured Mexican American children at a pediatric clinic in South Texas. Design and Methods: We identified 417 new patients from March 2019 to February 2020 (with exclusion of 104 newborns) and followed them until December 2021. Height and weight were measured to estimate Body Mass Index (BMI) . The percentage of overweight or obese (OW/OB) children was calculated at the first and last visit. Results: We had a total of 346 children at the end of the study. The average stature of the whole group was at the 48th percentile with 60% of the children at or below the 50th percentile based on CDC growth charts. Boys increased BMI from the 62.7th to 71.8th percentile (p<0.01) and girls increased from the 60th to the 70th percentile (p<0.02) . The distribution of BMI of the whole group indicated that 34.5% of children were OW/OB on the first visit and 49% were OW/OB at the last visit. Conclusion (s) : Our study exemplifies that the lockdown during the COVID-19 pandemic, which was associated with decreased physical activity, increased the BMI of children and increased associated comorbidities based on lab values. We have shown in previous studies that when BMI is in the OW/OB category, children have increased blood pressure, decreased high density lipoproteins, elevated liver enzymes, increased insulin resistance, larger kidneys, and fatty liver. These indicators place children at a higher risk for early development of hypertension, renal function decline, diabetes, and cardiovascular disease.

Serum NMR Profiling Reveals Differential Alterations in the Lipoproteome Induced by Pfizer-BioNTech Vaccine in COVID-19 Recovered Subjects and Naïve Subjects.

1H NMR spectra of sera have been used to define the changes induced by vaccination with Pfizer-BioNTech vaccine (2 shots, 21 days apart) in 10 COVID-19-recovered subjects and 10 COVID-19-naïve subjects at different time points, starting from before vaccination, then weekly until 7 days after second injection, and finally 1 month after the second dose. The data show that vaccination does not induce any significant variation in the metabolome, whereas it causes changes at the level of lipoproteins. The effects are different in the COVID-19-recovered subjects with respect to the naïve subjects, suggesting that a previous infection reduces the vaccine modulation of the lipoproteome composition.

The Current Status of Research on High-Density Lipoproteins (HDL): A Paradigm Shift from HDL Quantity to HDL Quality and HDL Functionality.

The quantity of high-density lipoproteins (HDL) is represented as the serum HDL-C concentration (mg/dL), while the HDL quality manifests as the diverse features of protein and lipid content, extent of oxidation, and extent of glycation. The HDL functionality represents several performance metrics of HDL, such as antioxidant, anti-inflammatory, and cholesterol efflux activities. The quantity and quality of HDL can change during one's lifetime, depending on infection, disease, and lifestyle, such as dietary habits, exercise, and smoking. The quantity of HDL can change according to age and gender, such as puberty, middle-aged symptoms, climacteric, and the menopause. HDL-C can decrease during disease states, such as acute infection, chronic inflammation, and autoimmune disease, while it can be increased by regular aerobic exercise and healthy food consumption. Generally, high HDL-C at the normal level is associated with good HDL quality and functionality. Nevertheless, high HDL quantity is not always accompanied by good HDL quality or functionality. The HDL quality concerns the morphology of the HDL, such as particle size, shape, and number. The HDL quality also depends on the composition of the HDL, such as apolipoproteins (apoA-I, apoA-II, apoC-III, serum amyloid A, and α-synuclein), cholesterol, and triglyceride. The HDL quality is also associated with the extent of HDL modification, such as glycation and oxidation, resulting in the multimerization of apoA-I, and the aggregation leads to amyloidogenesis. The HDL quality frequently determines the HDL functionality, which depends on the attached antioxidant enzyme activity, such as the paraoxonase and cholesterol efflux activity. Conventional HDL functionality is regression, the removal of cholesterol from atherosclerotic lesions, and the removal of oxidized species in low-density lipoproteins (LDL). Recently, HDL functionality was reported to expand the removal of ß-amyloid plaque and inhibit α-synuclein aggregation in the brain to attenuate Alzheimer's disease and Parkinson's disease, respectively. More recently, HDL functionality has been associated with the susceptibility and recovery ability of coronavirus disease 2019 (COVID-19) by inhibiting the activity of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The appearance of dysfunctional HDL is frequently associated with many acute infectious diseases and chronic aging-related diseases. An HDL can be a suitable biomarker to diagnose many diseases and their progression by monitoring the changes in its quantity and quality in terms of the antioxidant and anti-inflammatory abilities. An HDL can be a protein drug used for the removal of plaque and as a delivery vehicle for non-soluble drugs and genes. A dysfunctional HDL has poor HDL quality, such as a lower apoA-I content, lower antioxidant ability, smaller size, and ambiguous shape. The current review analyzes the recent advances in HDL quantity, quality, and functionality, depending on the health and disease state during one's lifetime.

Metabolic and Lipidomic Markers Differentiate COVID-19 From Non-Hospitalized and Other Intensive Care Patients.

Coronavirus disease 2019 (COVID-19) is a viral infection affecting multiple organ systems of great significance for metabolic processes. Thus, there is increasing interest in metabolic and lipoprotein signatures of the disease, and early analyses have demonstrated a metabolic pattern typical for atherosclerotic and hepatic damage in COVID-19 patients. However, it remains unclear whether this is specific for COVID-19 and whether the observed signature is caused by the disease or rather represents an underlying risk factor. To answer this question, we have analyzed 482 serum samples using nuclear magnetic resonance metabolomics, including longitudinally collected samples from 12 COVID-19 and 20 cardiogenic shock intensive care patients, samples from 18 severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibody-positive individuals, and single time point samples from 58 healthy controls. COVID-19 patients showed a distinct metabolic serum profile, including changes typical for severe dyslipidemia and a deeply altered metabolic status compared with healthy controls. Specifically, very-low-density lipoprotein and intermediate-density lipoprotein particles and associated apolipoprotein B and intermediate-density lipoprotein cholesterol were significantly increased, whereas cholesterol and apolipoprotein A2 were decreased. Moreover, a similarly perturbed profile was apparent when compared with other patients with cardiogenic shock who are in the intensive care unit when looking at a 1-week time course, highlighting close links between COVID-19 and lipid metabolism. The metabolic profile of COVID-19 patients distinguishes those from healthy controls and also from patients with cardiogenic shock. In contrast, anti-SARS-CoV-2 antibody-positive individuals without acute COVID-19 did not show a significantly perturbed metabolic profile compared with age- and sex-matched healthy controls, but SARS-CoV-2 antibody-titers correlated significantly with metabolic parameters, including levels of glycine, ApoA2, and small-sized low- and high-density lipoprotein subfractions. Our data suggest that COVID-19 is associated with dyslipidemia, which is not observed in anti-SARS-CoV-2 antibody-positive individuals who have not developed severe courses of the disease. This suggests that lipoprotein profiles may represent a confounding risk factor for COVID-19 with potential for patient stratification.

Pre-infection HDL-cholesterol levels and mortality among elderly patients infected with SARS-CoV-2.

BACKGROUND AND AIMS: Low HDL-cholesterol (HDLc) concentration is associated with a greater risk of infection-related mortality. We wanted to evaluate the relationship between pre-infection HDLc levels and mortality among older patients infected with SARS-Cov-2. METHODS: This is a population-based, cohort study, comprising all individuals residing in Madrid (Spain) born before 1 January 1945, and alive on 31 December 2019. Demographic, clinical, and analytical data were obtained from the primary care electronic clinical records. Confirmed SARS-CoV-2 infection was defined as a positive result in the RT-qPCR or in the antigen test. A death from COVID-19 was defined as that registered in the hospital chart, or as any death occurring in the 15 days following a confirmed SARS-CoV-2 infection. Data on infection, hospitalization, or death due to SAR-CoV-2 were collected from 1 March 2020 through 31 December 2020. RESULTS: Of the 593,342 individuals comprising the cohort, 36,966 had a SARS-CoV-2 infection during 2020, and at least one HDLc measurement in the previous five years. Among them, 9689 (26.2%) died from COVID-19. After adjustment for age and sex, the relative risk (95% confidence interval) of COVID-19 death across increasing quintiles of HDLc was 1.000, 0.896 (0.855-0.940), 0.816 (0.776-0.860), 0.758 (0.719-0.799), and 0.747 (0.708-0.787). The association was maintained after further adjustment for comorbidities, statin treatment and markers of malnutrition. While in females this association was linear, in males it showed a U-shaped curve. CONCLUSIONS: In older subjects, a higher HDLc measured before SARS-CoV-2 infection was associated with a lower risk of death.

The Role of High-Density Lipoprotein in COVID-19.

The current Coronavirus disease 2019 (COVID-19) pandemic has become a global challenge. Managing a large number of acutely ill patients in a short time, whilst reducing the fatality rate and dealing with complications, brings unique difficulties. The most striking pathophysiological features of patients with severe COVID-19 are dysregulated immune responses and abnormal coagulation function, which can result in multiple-organ failure and death. Normally metabolized high-density lipoprotein (HDL) performs several functions, including reverse cholesterol transport, direct binding to lipopolysaccharide (LPS) to neutralize LPS activity, regulation of inflammatory response, anti-thrombotic effects, antioxidant, and anti-apoptotic properties. Clinical data shows that significantly decreased HDL levels in patients with COVID-19 are correlated with both disease severity and mortality. However, the role of HDL in COVID-19 and its specific mechanism remain unclear. In this analysis, we review current evidence mainly in the following areas: firstly, the pathophysiological characteristics of COVID-19, secondly, the pleiotropic properties of HDL, thirdly, the changes and clinical significance of HDL in COVID-19, and fourthly the prospect of HDL-targeting therapy in COVID-19 to clarify the role of HDL in the pathogenesis of COVID-19 and discuss the potential of HDL therapy in COVID-19.

Importance of Apolipoprotein A-I and A-II Composition in HDL and Its Potential for Studying COVID-19 and SARS-CoV-2.

The composition and properties of apolipoprotein (apo) A-I and apoA-II in high-density lipoproteins (HDL) might be critical to SARS-CoV-2 infection via SR-BI and antiviral activity against COVID-19. HDL containing native apoA-I showed potent antiviral activity, while HDL containing glycated apoA-I or other apolipoproteins did not. However, there has been no report to elucidate the putative role of apoA-II in the antiviral activity of HDL.

Integrative Modeling of Plasma Metabolic and Lipoprotein Biomarkers of SARS-CoV-2 Infection in Spanish and Australian COVID-19 Patient Cohorts.

Quantitative plasma lipoprotein and metabolite profiles were measured on an autonomous community of the Basque Country (Spain) cohort consisting of hospitalized COVID-19 patients (n = 72) and a matched control group (n = 75) and a Western Australian (WA) cohort consisting of (n = 17) SARS-CoV-2 positives and (n = 20) healthy controls using 600 MHz 1H nuclear magnetic resonance (NMR) spectroscopy. Spanish samples were measured in two laboratories using one-dimensional (1D) solvent-suppressed and T2-filtered methods with in vitro diagnostic quantification of lipoproteins and metabolites. SARS-CoV-2 positive patients and healthy controls from both populations were modeled and cross-projected to estimate the biological similarities and validate biomarkers. Using the top 15 most discriminatory variables enabled construction of a cross-predictive model with 100% sensitivity and specificity (within populations) and 100% sensitivity and 82% specificity (between populations). Minor differences were observed between the control metabolic variables in the two cohorts, but the lipoproteins were virtually indistinguishable. We observed highly significant infection-related reductions in high-density lipoprotein (HDL) subfraction 4 phospholipids, apolipoproteins A1 and A2,that have previously been associated with negative regulation of blood coagulation and fibrinolysis. The Spanish and Australian diagnostic SARS-CoV-2 biomarkers were mathematically and biologically equivalent, demonstrating that NMR-based technologies are suitable for the study of the comparative pathology of COVID-19 via plasma phenotyping.