Increase in gut permeability and oxidized ldl is associated with post-acute sequelae of SARS-CoV-2.

Background: Post-acute sequelae of SARS-CoV-2 (PASC) is marked by persistent or newly developing symptoms beyond 4 weeks of infection. Investigating gut integrity, oxidized lipids and inflammatory markers is important for understanding PASC pathogenesis. Methods: A cross-sectional study including COVID+ with PASC, COVID+ without PASC, and COVID-negative (COVID-) participants. We measured plasma markers by enzyme-linked immunosorbent assay to assess intestinal permeability (ZONULIN), microbial translocation (lipopolysaccharide-binding protein or LBP), systemic inflammation (high-sensitivity C-reactive protein or hs-CRP), and oxidized low-density lipoprotein (Ox-LDL). Results: 415 participants were enrolled in this study; 37.83% (n=157) had prior COVID diagnosis and among COVID+, 54% (n=85) had PASC. The median zonulin among COVID- was 3.37 (IQR: 2.13, 4.91) mg/mL, 3.43 (IQR: 1.65, 5.25) mg/mL among COVID+ no PASC, and highest [4.76 (IQR: 3.2, 7.35) mg/mL] among COVID+ PASC+ (p<.0001). The median ox-LDL among COVID- was 47.02 (IQR: 35.52, 62.77) U/L, 57.24 (IQR: 40.7, 75.37) U/L among COVID+ No PASC, and the highest [76.75 (IQR: 59.95, 103.28) U/L] among COVID+ PASC+ (p<.0001). COVID+ PASC+ was positively associated with zonulin (p=0.0002) and ox-LDL (p<.0001), and COVID- was negatively associated with ox-LDL (p=0.01), compared to COVID+ No PASC. Every unit increase in zonulin was associated with 44% higher predicted odds of having PASC [aOR: 1.44 (95%CI: 1.1, 1.9)] and every one-unit increase in ox-LDL was associated with more than four-fold increased odds of having PASC [aOR: 2.44 (95%CI: 1.67, 3.55)]. Conclusions: PASC is associated with increased gut permeability and oxidized lipids. Further studies are needed to clarify whether these relationships are causal which could lead to targeted therapeutics.

Potential of Hesperidin in the Medicinal Field

Hesperidin has gained major interest recently due to the outbreak of COVID-19. The traction has led to more research being conducted on the compound hesperidin. Recent studies have shown its anti-inflammatory and anti-viral attributes, which have beneficial effects on severe acute respiratory syndrome (SARS-CoV-2). Hesperidin has also shown unique effects on the protein of SARS-CoV-2, which lead to a good preventative measure for SARS-CoV-2. Hesperidin also causes a suppression of appetite, which helps to combat obesity through the release of cholecystokinin. Furthermore, hesperidin has shown cardioprotective properties, which cause an increase in plasma high-density lipoprotein levels and a decrease in plasma low-density lipoprotein levels. Hesperidin is also used in combination with the Japanese herb Rikkunshito, which has shown potential in a discovery of a new drug for gastrointestinal motility as hesperidin can depolarize pacemaker potential in interstitial cells of Cajal (ICC). The chemo-preventive effects of hesperidin are caused by its antioxidant effect, which may prevent tissue necrosis due to oxidative stress. The photo-protective effect of hesperidin can reduce the damage to the skin caused by UV rays. Hesperidin also possesses wound-healing properties.Copyright © 2023 Bentham Science Publishers.

Lipid Lowering Natural Products Targeting hPCSK9 May Prevent the Severity of COVID-19 Infection

Background: The deadly outbreak of COVID-19 disease caused by novel SARS CoV2 has created an unprecedented global health crisis affecting every sectors of human life and enor-mous damage to world's economy. With >16.1 million infections and >650,000 deaths worldwide as of July 27, 2020, there is no treatment for this disease neither is there any available vaccine. Seri-ous research efforts are ongoing on all fronts including treatment, prevention and diagnosis to combat the spread of this infection. A number of targets that include both viral and host proteins have been identified and became part of intense investigation. In this respect the viral surface spike (S) glycoprotein caught the attention most. It is cleaved by multiple host proteases to allow recognition by host receptor human Angiotensin Converting Enzyme2 (hACE2) leading to fusion and viral re-plication. Natural products, small compounds, antioxidants, peptides, proteins, oligonucleotides, antibodies and other compounds are under investigation for development of antiviral agents against COVID-19. Objective(s): Recently cholesterol lowering phytocompounds Quercetin, Swertiamarin and Berberine which promote human Low Density Lipoprotein Receptor (hLDLR) via inhibition of human Pro-protein Convertase Subtilisin Kexin9 (hPCSK9) have been shown to block viral infections caused by ebola, influenza, Respiratory Syncytial Virus (RSV), Hepatitis C virus (HCV) and other RNA type viruses. Since SARS CoV2 is a RNA virus with similar genetic structure and infection machin-ery, it is hypothesised that these phytocompounds may also exhibit antiviral property against COVID-19. Method(s): Our above concept is based on recently published studies as well as our herein presented in silico modeling and computational data which suggested strong interactions of hPCSK9 with above phytocompounds and most importantly with hACE2 following its complexation with receptor binding domain (RBD) of SARS CoV2 S protein. Result(s): These results and a proposed schematic model showing association of hPCSK9 with SARS CoV2 infection are presented in this manuscript. It is proposed that hPCSK9 plays the role of a co-receptor in binding with hACE2:RBD complex and thereby facilitates viral fusion. Conclusion(s): Our studies suggest that PCSK9 inhibitors may provide beneficial effect against COVID-19 infection by retarding viral fusion through displacement of bound hPCSK9 from its complex with ACE2:RBD of SARS CoV2 S protein.Copyright © 2021 Bentham Science Publishers.

A study of relationship between lipid profile and severity of SARS-CoV-2

COVID-19 is a severe acute respiratory disease caused by coronavirus 2. While many biochemical alterations have been studied in patients with COVID-19, only a few studies were available to explore the relationship between serum lipid profile values and the severity of SARS COVID-19 infection. A cross-sectional study was conducted at Chettinad Hospital and Research Institute on 128 patients infected with SARS COVID-19 from March 2020 to September 2020. It was an age and sex-matched study. Patients were categorized into mild and severe based on the signs and symptoms. A fasting serum lipid profile and IL-6 levels were measured and Pearson's correlation analysis was done. There was a highly significant decrease in the median and IQR levels of TC, HDL, and LDL in severe cases as compared to mild cases [TC - mild: (256,64), severe (125,44), HDL - mild (46,11), severe (25,13), and LDL - mild (170,48), severe (76,36)]. TGL showed a significant decrease [mild: (170,67), severe:(110,69)]. IL-6 showed a significant increase in severe cases when compared to mild cases [mild:(20,37), severe:(62,105)]. Pearson's correlation analysis showed a significant inverse relationship between the levels of TC, HDL, and IL-6. However, TGL and LDL showed inverse but no significant relationship with IL-6. As the severity of COVID-19 increases, lipid profile levels start decreasing. Hypolipidemia is a pathognomic finding in severe SARS COVID-19 infection.

Low HDL-c levels at admission are associated with greater severity and worse clinical outcomes in patients with COVID-19 disease.

Background and aims: HDL particles may act to buffer host cells from excessive inflammatory mediators. The aim of this study is to investigate if the lipid profile provides a prognostic biomarker for COVID-19 outcomes. Methods: This was a prospective study of the characteristics of 125 adult COVID-19 patients with a lipid profile performed on the day of admission analyzed with regard to clinical outcomes. Results: Seventy-seven patients (61.2%) were men, with a mean age of 66.3 (15.6) years. 54.1% had bilateral pneumonia. The all-cause mortality rate during hospitalization was 20.8%. We found a direct association between more severe disease assessed by the WHO classification, admission to the ICU and death with more pronounced lymphopenia, higher levels of CRP, ferritin (p < 0.001), D-dímer and lactate dehydrogenase (LDH) all statistically significant. Lower leves of HDL-c and LDL-c were also associated with a worse WHO classification, ICU admission, and death,. HDL-c levels were inversely correlated with inflammatory markers CRP (r = -0.333; p < 0.001), ferritin (r = -0.354; p < 0.001), D-dímer (r = -0.214; p < 0.001), LDH (r = -0.209; p < 0.001. LDL-c levels were significantly associated with CRP (r = -0.320; p < 0.001) and LDH (r = -0.269; p < 0.001). ROC curves showed that HDL [AUC = 0.737(0.586-0.887), p = 0.005] and lymphocytes [AUC = 0.672(0.497-0.847], p < 0.043] had the best prognostic accuracy to predict death. In a multivariate analysis, HDL-c (ß = -0.146(0.770-0.971), p = 0.014) and urea (ß = 0.029(1.003-1.057), p = 0.027) predicted mortality. Conclusion: Hypolipidemia including HDL levels at admission identifies patients with a higher risk of death and worse clinical manifestations who may require more intensive care.

Can circulating oxidative stress-related biomarkers be used as an early prognostic marker for COVID-19?

Background: Oxidative stress plays an important role in the pathogenesis of many diseases. This study aimed to investigate the relationship between nuclear factor kappa B (NF-κB) and oxidative stress and the severity of the disease in new COVID-19 patients, and, to compare the levels of NF-κB, oxidized LDL (oxLDL), and lectin-like oxidized-LDL receptor-1 (LOX-1) with oxygen saturation, which is an indicator of the severity parameters of the disease in COVID-19 patients. Methods: In this prospective study, 100 COVID-19 patients and 100 healthy subjects were selected. Results: LOX-1, NF-κB, and oxLDL were found to be higher in COVID-19 patients compared to the healthy subjects (p < 0.001 for all). According to the results of correlation analysis, it was found that there was no significant relationship between oxygen saturation and LOX-1, NF-κB and oxLDL parameters. There was significant relationship between oxLDL with LOX-1 and NF-κB in patients with COVID-19 disease. ROC analysis results of the highest discrimination power were oxLDL (AUC: 0.955, CI: 0.904-1.000; sensitivity: 77%, and specificity: 100%, for cutoff: 127.944 ng/l) indicating COVID-19. Conclusion: Oxidative stress plays an essential role in COVID-19. NF-κB, oxLDL, and LOX-1 seem to represent good markers in COVID-19. Our study also showed that oxLDL has the highest power in distinguishing patients with COVID-19 from the healthy subjects.

Plasma Apolipoprotein Concentrations Are Highly Altered in Severe Intensive Care Unit COVID-19 Patients: Preliminary Results from the LIPICOR Cohort Study.

SARS-CoV-2 infection goes beyond acute pneumonia, as it also impacts lipid metabolism. Decreased HDL-C and LDL-C levels have been reported in patients with COVID-19. The lipid profile is a less robust biochemical marker than apolipoproteins, components of lipoproteins. However, the association of apolipoprotein levels during COVID-19 is not well described and understood. The objective of our study is to measure plasma levels of 14 apolipoproteins in patients with COVID-19 and to evaluate the relationships between apolipoprotein levels, severity factors and patient outcomes. From November to March 2021, 44 patients were recruited on admission to the intensive care unit because of COVID-19. Fourteen apolipoproteins and LCAT were measured by LC-MS/MS in plasma of 44 COVID-19 patients on admission to the ICU and 44 healthy control subjects. Absolute apolipoprotein concentrations were compared between COVID-19 patients and controls. Plasma apolipoproteins (Apo) A (I, II, IV), C(I, II), D, H, J and M and LCAT were lower in COVID-19 patients, whereas Apo E was higher. COVID-19 severity factors such as PaO2/FiO2 ratio, SO-FA score and CRP were correlated with certain apolipoproteins. Lower Apo B100 and LCAT levels were observed in non-survivors of COVID-19 versus survivors. To conclude, in this study, lipid and apolipoprotein profiles are altered in COVID-19 patients. Low Apo B100 and LCAT levels may be predictive of non-survival in COVID-19 patients.

The bidirectional interaction of COVID-19 infections and lipoproteins.

COVID-19 infections decrease total cholesterol, LDL-C, HDL-C, and apolipoprotein A-I, A-II, and B levels while triglyceride levels may be increased or inappropriately normal for the poor nutritional status. The degree of reduction in total cholesterol, LDL-C, HDL-C, and apolipoprotein A-I are predictive of mortality. With recovery lipid/lipoprotein levels return towards pre-infection levels and studies have even suggested an increased risk of dyslipidemia post-COVID-19 infection. The potential mechanisms for these changes in lipid and lipoprotein levels are discussed. Decreased HDL-C and apolipoprotein A-I levels measured many years prior to COVID-19 infections are associated with an increased risk of severe COVID-19 infections while LDL-C, apolipoprotein B, Lp (a), and triglyceride levels were not consistently associated with an increased risk. Finally, data suggest that omega-3-fatty acids and PCSK9 inhibitors may reduce the severity of COVID-19 infections. Thus, COVID-19 infections alter lipid/lipoprotein levels and HDL-C levels may affect the risk of developing COVID-19 infections.

Autoimmune Reaction Associated With Long COVID Syndrome and Cardiovascular Disease: A Genetic Case Report.

A 35-year-old woman with history of cardiovascular disease presented with shortness of breath, lightheadedness, fatigue, chest pain, and premature ventricular contractions 3 weeks after her second COVID-19 vaccine. Symptoms subsided following catheter ablation and ibuprofen except for chest pain and fatigue, which persisted following ablation and subsequent SARS-CoV-2 infection. The case suggests causal associations between COVID-19 vaccine/infection and recurrence of cardiovascular disease, including long-COVID-like symptoms. (Level of Difficulty: Advanced.).

Hypercholesterolemia After COVID-19: Time to Include Lipoprotein X Among the Differential Diagnoses.

Background: Lipoprotein X (LpX) is an abnormal lipoprotein composed of phospholipids, free cholesterol, and albumin. Its overaccumulation is an infrequent cause of hyperlipidemia, which oftentimes presents in patients with cholestatic liver disease. The aim is to present the first 2 cases of patients with post-COVID cholangiopathy and LpX overaccumulation. Case Report: We present 2 female patients (ie, a 34-year-old [patient 1] and a 56-year-old [patient 2]), who had complicated courses of COVID-19, requiring prolonged mechanical ventilation (>4 weeks). One month after discharge, patient 1 presented with abdominal pain. Patient 2 had gangrenous cholecystitis and later developed recurrent elevation of alkaline phosphatase and bilirubin. Both patients were diagnosed with cholestatic liver disease. During outpatient follow-up both patients were found to have elevated plasma low-density lipoprotein cholesterol (LDL-C) in routine lipid panels (723 mg/dL and 1389 mg/dL, respectively). Both patients underwent various treatments for elevated LDL-C before referral to endocrinology. Patients were diagnosed with LpX overaccumulation from post-COVID-19 cholangiopathy. In both patients, LDL-C fluctuations seen in routine lipid panels (affected by LpX levels) were tightly correlated with changes in alkaline phosphate and bilirubin. Discussion: Our patients represent the first report of LpX overaccumulation in patients with post-COVID-19 cholangiopathy. Whether LpX accumulation is only the result of liver dysfunction, or COVID-19 infection plays a direct role in elevated LpX levels is still unknown. Conclusion: In patients with complicated courses of COVID-19, LpX overaccumulation should be considered when a routine lipid panel shows significant LDL-C elevations. Awareness among health care providers regarding LpX is important to avoid unnecessary workup and treatment.

Effects of COVID-19 Pandemic and Lockdown on Monitoring and Treatment Balance of Finnish Coronary Heart Disease and Type 2 Diabetes Patients.

Purpose: We aimed to examine the effect of the COVID-19 pandemic and lockdown on monitoring and treatment balance of Finnish coronary heart disease (CHD) and type 2 diabetes (T2D) patients. Patients and Methods: We used data from the electronic health records on 1604 CHD and 10,136 T2D patients aged 18‒85 years in Eastern Finland. Measurement and levels of low-density lipoprotein cholesterol (LDL) of CHD patients and glycated haemoglobin (HbA1c) of T2D patients were assessed monthly during January 2019-June 2021. Interrupted time-series analysis design was utilized to examine the effect of the lockdown on proportion of patients monitored and treatment balance. Results: Reductions in frequencies of LDL testing of CHD and HbA1c testing of T2D patients were observed during the national lockdown. Downward trend in average LDL was observed from January 2019 until June 2021. Average HbA1c values increased from January 2019 to March 2020 with an additional increase by 2.04 mmol/mol (0.80 to 3.29) in April 2020. However, there was a downward trend in monthly average HbA1c during the lockdown until June 2021 with an additional change in level by 0.61 mmol/mol (95% CI 0.06 to 1.16) in July 2020. Conclusion: The lockdown decreased the frequency of monitoring among both CHD and T2D patients. Meanwhile, monthly average LDL had a steadily improving pattern in CHD patients during the follow-up while temporary worsening in HbA1c in patients with T2D was observed at the time of the lockdown. The lockdown may have introduced selection in patients who had their treatment outcomes monitored. Better self-management of risk factors among patients is also possible.

Induction of Hypoxic Response in Caco-2 Cells Promote the Expression of Genes Involved in SARS-CoV-2 Endocytosis and Transcytosis.

In the present manuscript we analyzed the influence of hypoxic response in Caco-2 cells on the expression of genes and miRNAs involved in the mechanisms of intracellular transport of SARS-CoV-2 viral particles, especially endocytosis and transcytosis. With the use of RNA sequencing of Caco-2 cells treated with hypoxia-inducing oxyquinoline derivative, we showed two-fold increase in the expression of the main SARS-CoV-2 receptor ACE2. Expression of the non-canonical receptor TFRC was also elevated. We also observed a significant increase in the expression levels of genes from the low-density lipoprotein (LDL) receptor family, which play a crucial role in the transcytosis: LDLR, LRP1, LRP4, and LRP5. Upregulation of LDLR was coupled with the downregulation of hsa-miR-148a-3p, which can directly bind to LDLR mRNA. Thus, the hypoxic response in Caco-2 cells includes upregulation of genes involved in the mechanisms of endocytosis and transcytosis of SARS-CoV-2 viral particles.

Seasonal variations and the influence of COVID-19 pandemic on hemoglobin A1c, glycoalbumin, and low-density lipoprotein cholesterol.

Aim: The purpose of the study was to investigate seasonal variations in HbA1c, GA and LDL-C and to examine the effects of the COVID-19 pandemic on these variations and on glycemic and lipid control themselves in patients with type 2 diabetes. Patients and methods: The subjects were outpatients with type 2 diabetes who had received standard treatment for glycemic control for more than 3 years. Data for patients who visited our hospital from January 2021 to March 2021 were retrospectively investigated based on electronic medical records. Results: HbA1c showed seasonal variation (high in winter-spring and low in summer-autumn), and this was similar during the COVID-19 pandemic. However, the mean HbA1c over 1 year was significantly elevated during the COVID-19 pandemic (7.53 ± 1.02% in 2020) compared with the previous 2 years: (7.34 ± 0.91 in 2018, 7.39 ± 0.93 in 2019; 2020 vs. 2018; 0.19%, P < 0.001; 2020 vs. 2019; 0.14%, P = 0.0013) and the difference was larger in winter. GA showed no apparent seasonal variation, but mean GA during the COVID-19 pandemic was elevated compared with earlier years (2020 vs. 2018, P < 0.001; 2020 vs. 2019, P < 0.001). LDL-C did not show apparent seasonal variation and was unaffected by COVID-19 pandemic. Conclusion: The COVID-19 pandemic influenced mean HbA1c and GA levels over 1 year, but did not affect seasonal variations, while LDL-C was not affected by COVID-19. Observation of these levels over a longer period is warranted to determine the longer-term influence of the COVID-19 pandemic.

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.

Impact of the COVID-19 pandemic in the lipid control of the patients that start PCSK9 inhibitors

Objectives MEMOGAL study (NCT04319081) is aimed at evaluating changes in cognitive function in patients treated with PCSK9 inhibitors (PCSK9i). This is the first analysis: (1) discussion about the role of the Hospital Pharmacists during the pandemic, and also the assessment of the impact of COVID-19 in the lipid control;(2) descriptive analysis;(3) effectiveness in LDL cholesterol (LDL-c) reduction of alirocumab and evolocumab;(4) communicate PCSK9i safety. Material and methods It is a prospective Real-World Evidence analysis of patients that take PCSK9i for the first time in the usual clinical practice, and they are included after the first dispensation in the public pharmacy consultations of 12 Hospitals in Galicia from May 2020 to April 2021. Baseline values of LDL-c are the previous values before taking PCSK9 and the follow-up values are in 6 months time. Results 89 patients were included. 86.5% with cardiovascular disease and 53.9% with statin intolerances. 78.8% of the patients were treated with high intensity statins. Statins most used were rosuvastatin (34.1%) and atorvastatin (20.5%). Baseline value of LDL-c was 148 mg/dL and the follow-up value was 71 mg/dL. The baseline value of patients treated with alirocumab (N = 43) was 144 mg/dL and 73 mg/dL in the follow-up. With evolocumab (N = 46) was 151 mg/dL in basaline and 69 mg/dL in follow-up. The LDLc- reduction was 51.21% with evolocumab and 51.05% with alirocumab. 43.1% of the patients showed values >70 mg/dL in six month time;19.4% between 69 mg/dl and 55 mg/dL and 37.5% <55 mg/dL. 58.3% of the patients achieved a reduction >50% of LDL-c. The adverse events were: injection point reaction (N = 2), myalgias (N = 1), flu-like symptoms (N = 1) and neurocognitive worsening (N = 1). Conclusions (1) Despite the number of prescriptions was reduced because of the pandemic, the lipid control was not affected. (2) Half of the patients treated with PSCK9i is due to statins intolerance and the 86% is for secondary prevention. (2) The reduction results were similar to pivotal clinical trials. Despite this, 39% of the total of the patients and 60% of patients with dual teraphy did not reach the goal of ESC/EAS guidelines (< 55 mg/dL and/or reduction > 50%). There were not significant differences between evolocumab and alirocumab: 51.21% vs 51.05% (P = .972). (3) There were not any adverse events of special interest. The possible neurocognitive worsening will be studied as the primary endpoint once the MEMOGAL study has been completed. Resumen Objetivos El estudio MEMOGAL (NCT04319081) está dirigido a evaluar cambios en la función cognitiva en pacientes tratados con inhibidores de la PCSK9 (iPCSK9). Se realiza primer análisis: 1) discutir el papel de los farmacéuticos hospitalarios durante de la pandemia, así como evaluar el impacto de la misma en el control lipídico;2) análisis descriptivo;3) eficacia en reducción de colesterol-LDL (c-LDL) de alirocumab y v;y 4) reportar seguridad de los iPCSK9. Material y métodos Se trata de un análisis prospectivo en vida real de pacientes tratados por primera vez con iPCSK9 en la práctica clínica habitual e incluidos en su primera dispensación en las consultas de farmacia de 12 hospitales de Galicia desde mayo de 2020-abril de 2021. Los valores basales de c-LDL son los previos al inicio del tratamiento con iPCSK9 y como seguimiento los valores a los 6 meses. Resultados Se incluyeron 89 pacientes. El 86,5% con enfermedad cardiovascular y un 53,9% intolerancia a las estatinas. Un 78,8% de los pacientes fueron tratados con estatinas de alta intensidad. Las estatinas más usadas fueron rosuvastatina (34,1%) y atorvastatina (20,5%). El nivel basal de c-LDL fue 148 mg/dl y de 71 mg/dl al seguimiento. Los pacientes tratados con alirocumab (n = 43) presentaban valores basales de 144 mg/dl y de 73 mg/dl al seguimiento y con evolocumab (n = 46) de 151 mg/dl basal y 69 mg/dl al seguimiento. La reducción de c-LDL fue para evolocumab 51,21% y alirocumab 51,05%. El 43,1% presentaba a los 6 meses valores > 70 mg/dl, el 19,4% entre 55 y 69 mg/dl y el 37,5% < 55 mg/dl. Los pacientes que obtuvieron una reducción > 50% de c-LDL fueron el 58,3%. Los eventos adversos presentados fueron: reacción en el lugar de inyección (n = 2), mialgias (n = 1), síntomas pseudogripales (n = 1) y deterioro neurocognitivo (n = 1). Conclusiones 1) A pesar de haber disminuido el número de prescripciones de iPCSK9 durante la pandemia, el control lipídico de estos pacientes no se ha visto afectado;2) la mitad de los pacientes tratados con iPSCK9 se debe a intolerancia a estatinas y el 86% es en prevención secundaria;3) se presentaron valores de reducción similares a los ensayos clínicos pivotales. A pesar de esto, un 39% del total y un 60% en doble terapia no alcanzaron las recomendaciones de las guías ESC/EAS (< 55 mg/dl y/o reducción > 50%). No hubo diferencias significativas entre evolocumab y alirocumab: 51,21% vs. 51,05% (p = 0,972);y 4) no se observaron eventos de especial interés con el uso de estos fármacos. El posible deterioro cognitivo será analizado como variable principal una vez completado el estudio MEMOGAL.

HDL cholesterol levels and susceptibility to COVID-19.

BACKGROUND: Host cell-membrane cholesterol, an important player in viral infections, is in constant interaction with serum high-density lipoprotein-cholesterol (HDL-C) and low-density lipoprotein-cholesterol (LDL-C). Low serum lipid levels during hospital admission are associated with COVID-19 severity. However, the effect of antecedent serum lipid levels on SARS-CoV-2 infection risk has not been explored. METHODS: From our retrospective cohort from the Arkansas Clinical Data-Repository, we used log-binomial regression to assess the risk of SARS-CoV-2 infection among the trajectories of lipid levels during the 2 years antecedent to COVID-19 testing, identified using group-based-trajectory modelling. We used mixed-effects linear regression to assess the serum lipid level trends followed up to the time of, and 2-months following COVID-19 testing. FINDINGS: Among the 11001 individuals with a median age of 59 years (IQR 46-70), 1340 (12.2%) tested positive for COVID-19. The highest trajectory for antecedent serum HDL-C was associated with the lowest SARS-CoV-2 infection risk (RR 0.63, 95%CI 0.46-0.86). Antecedent serum LDL-C, total cholesterol (TC), and triglycerides (TG) were not independently associated with SARS-CoV-2 infection risk. In COVID-19 patients, serum HDL-C (-7.7, 95%CI -9.8 to -5.5 mg/dL), and LDL-C (-6.29, 95%CI -12.2 to -0.37 mg/dL), but not TG levels, decreased transiently at the time of testing. INTERPRETATION: Higher antecedent serum HDL-C, but not LDL-C, TC, or TG, levels were associated with a lower SARS-CoV-2 infection risk. Serum HDL-C, and LDL-C levels declined transiently at the time of infection. Further studies are needed to determine the potential role of lipid-modulating therapies in the prevention and management of COVID-19. FUNDING: Research reported in this publication was supported by the National Center for Advancing Translational Sciences of the National Institutes of Health under Award Number UL1 TR003107.

Health effects and known pathology associated with the use of E-cigarettes.

In recent years, new nicotine delivery methods have emerged, and many users are choosing electronic cigarettes (e-cigarettes) over traditional tobacco cigarettes. E-cigarette use is very popular among adolescents, with more than 3.5 million currently using these products in the US. Despite the increased prevalence of e-cigarette use, there is limited knowledge regarding the health impact of e-cigarettes on the general population. Based on published findings by others, E-cigarette is associated with lung injury outbreak, which increased health and safety concerns related to consuming this product. Different components of e-cigarettes, including food-safe liquid solvents and flavorings, can cause health issues related to pneumonia, pulmonary injury, and bronchiolitis. In addition, e-cigarettes contain alarmingly high levels of carcinogens and toxicants that may have long-lasting effects on other organ systems, including the development of neurological manifestations, lung cancer, cardiovascular disorders, and tooth decay. Despite the well- documented potential for harm, e-cigarettes do not appear to increase susceptibility to SARS-CoV- 2 infection. Furthermore, some studies have found that e-cigarette users experience improvements in lung health and minimal adverse effects. Therefore, more studies are needed to provide a definitive conclusion on the long-term safety of e-cigarettes. The purpose of this review is to inform the readers about the possible health-risks associated with the use of e-cigarettes, especially among the group of young and young-adults, from a molecular biology point of view.