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Infections with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) cause coronavirus disease 2019 (COVID-19), a disease with very heterogeneous symptoms. Dyslipidaemia is prevalent in at least 20% of Europeans, and dyslipidaemia before SARS-CoV-2 infection increases the risk for severe COVID-19 and mortality by 139%. Many reports described reduced serum cholesterol levels in virus-infected patients, in particular in those with severe disease. The liver is the major organ for lipid homeostasis and hepatic dysfunction appears to occur in one in five patients infected with SARS-CoV-2. Thus, SARS-CoV-2 infection, COVID-19 disease severity and liver injury may be related to impaired cholesterol homeostasis. These observations prompted efforts to assess the therapeutic opportunities of cholesterol-lowering medications to reduce COVID-19 severity. The majority of studies implicate statins to have beneficial effects on disease severity and outcome in COVID-19. Proprotein convertase subtilisin/kexin type 9 (PCSK9) antibodies have also shown potential to protect against COVID-19. This review describes the relationship between systemic cholesterol levels, liver injury and COVID-19 disease severity. The potential effects of statins and PCSK9 in COVID-19 are summarised. Finally, the relationship between cholesterol and lung function, the first organ to be affected by SARS-CoV-2, is described. [ABSTRACT FROM AUTHOR]

Bacterial and fungal superinfections are common in COVID-19, and early diagnosis can enable timely intervention. Serum calprotectin levels increase with bacterial, fungal, and viral infections. This study evaluated serum calprotectin as a diagnostic and prognostic tool for microbial superinfections in COVID-19. Serum samples from adult patients with moderate and severe COVID-19 were collected during hospitalization from 2020 to 2024. Calprotectin levels were measured using an enzyme-linked immunosorbent assay in 63 patients with moderate COVID-19, 60 patients with severe COVID-19, and 34 healthy individuals. Calprotectin serum levels were elevated in patients with moderate COVID-19 compared with controls, and these levels were further increased in the severe cases. Patients with severe COVID-19 and vancomycin-resistant enterococci (VRE) bacteremia had elevated calprotectin levels, but their C-reactive protein and procalcitonin levels were not increased. Fungal superinfections and herpes simplex virus reactivation did not change the calprotectin levels. A calprotectin concentration of 31.29 µg/mL can be used to diagnose VRE bloodstream infection with 60% sensitivity and 96% specificity. These data suggest that serum calprotectin may be a promising biomarker for the early detection of VRE bloodstream infections in patients with COVID-19. [ABSTRACT FROM AUTHOR]

Background/Objectives: Chemerin is an adipokine involved in inflammatory and metabolic diseases, and its circulating levels have been associated with inflammatory parameters in various patient cohorts. Severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) infection, which causes COVID-19, triggers inflammatory pathways. However, the association between serum chemerin levels and COVID-19 disease severity and outcomes has not been definitively established. Methods: In this study, serum chemerin levels were analyzed in 64 patients with moderate COVID-19 and 60 patients with severe disease. Results: The results showed that serum chemerin levels were comparable between these two groups and slightly higher than in healthy controls. Notably, COVID-19 patients with hypertension exhibited elevated serum chemerin levels, while those with liver cirrhosis had lower levels. When patients with these comorbidities were excluded from the analyses, serum chemerin levels in COVID-19 patients were similar to those in healthy controls. Positive correlations were observed between serum chemerin levels and markers such as alkaline phosphatase, C-reactive protein, eosinophils, and lymphocytes in the entire cohort, as well as in the subgroup excluding patients with hypertension and cirrhosis. Additionally, urinary chemerin levels were comparable between COVID-19 patients and controls, and neither hypertension nor dialysis significantly affected urinary chemerin levels. Both survivors and non-survivors had similar serum and urinary chemerin levels. Conclusions: In conclusion, this study suggests that comorbidities such as arterial hypertension and liver cirrhosis do have a more significant impact on serum chemerin levels than SARS-CoV-2 infection itself. [ABSTRACT FROM AUTHOR]

Amyloid beta (Aβ) plays a major role in the pathogenesis of Alzheimer's disease and, more recently, has been shown to protect against liver fibrosis. Therefore, we studied Aβ-42 levels and the expression of genes involved in the generation, degradation, and transport of Aβ proteins in liver samples from patients at different stages of metabolic dysfunction-associated liver disease (MASLD) and under steatotic conditions in vitro/in vivo. Amyloid precursor protein (APP), key Aβ-metabolizing proteins, and Aβ-42 were analyzed using RT-PCR, Western blotting, Luminex analysis in steatotic in vitro and fatty liver mouse models, and TaqMan qRT-PCR analysis in hepatic samples from patients with MASLD. Hepatocytes loaded with palmitic acid induced APP, presenilin, and neprilysin (NEP) expression, which was reversed by oleic acid. Increased APP and NEP, decreased BACE1, and unchanged Aβ-42 protein levels were found in the steatotic mouse liver compared to the normal liver. Aβ-42 concentrations were low in MASLD samples of patients with moderate to severe fibrosis compared to the livers of patients with mild or no MASLD. Consistent with the reduced Aβ-42 levels, the mRNA expression of proteins involved in APP degradation (ADAM9/10/17, BACE2) and Aβ-42 cleavage (MMP2/7/9, ACE) was increased. In the steatotic liver, the expression of APP- and Aβ-metabolizing proteins is increased, most likely related to oxidative stress, but does not affect hepatic Aβ-42 levels. Consistent with our previous findings, low Aβ-42 levels in patients with liver fibrosis appear to be caused by the reduced production and enhanced non-amyloidogenic processing of APP. [ABSTRACT FROM AUTHOR]

Phosphatidylcholine (PC) is an essential lipid for liver health and lipoprotein metabolism, but its circulating levels have rarely been studied in patients with cirrhosis. Chronic hepatitis C virus (HCV) infection causes lipid abnormalities and is a major cause of cirrhosis. Effective HCV elimination with direct-acting antivirals (DAAs) is associated with the normalization of serum low-density lipoprotein cholesterol levels. Since PC is abundant in all lipoprotein particles, this study analyzed the association between serum PC species levels and liver cirrhosis before and after HCV eradication. Therefore, 27 PC species were measured by Fourier Transform Mass Spectrometry in the serum of 178 patients with chronic HCV infection at baseline and in 176 of these patients at the end of therapy. The PC species did not correlate with viral load, and the levels of 13 PC species were reduced in patients infected with genotype 3a compared to those affected with genotype 1. Four PC species were slightly elevated 12 weeks after DAA initiation, and genotype-related changes were largely normalized. Patients with HCV and cirrhosis had higher serum levels of PC 30:0 and 32:0 before and at the end of therapy. PC species containing polyunsaturated fatty acids were mostly decreased in cirrhosis. The levels of polyunsaturated, but not saturated, PC species were inversely correlated with the model of the end-stage liver disease score. A receiver operating characteristic curve analysis showed area under the curve values of 0.814 and 0.826 for PC 32:0 and 0.917 and 0.914 for % PC 32:0 (relative to the total PC levels) for the classification of cirrhosis at baseline and at the end of therapy, respectively. In conclusion, the specific upregulation of PC 32:0 in cirrhosis before and after therapy may be of diagnostic value in HCV-related cirrhosis. [ABSTRACT FROM AUTHOR]

SARS-CoV-2 infection was shown to induce proprotein convertase subtilisin/kexin type 9 (PCSK9) plasma levels in sepsis. Here, we investigate the association between serum PCSK9 levels and disease severity. PCSK9 was measured in serum of 55 controls, 40 patients with moderate and 60 patients with severe COVID-19 disease. Serum PCSK9 was elevated in moderate COVID-19 compared to controls and further increased in severe cases. PCSK9 levels were not associated with C-reactive protein, bacterial superinfections, interventions, or survival in patients with severe COVID-19. PCSK9 regulates circulating cholesterol levels, and 15 cholesteryl ester (CE) species and free cholesterol (FC) were quantified by direct flow injection analysis using a high-resolution hybrid quadrupole-Orbitrap mass spectrometer. Most CE species with shorter fatty acid chains were decreased in severe compared to moderate COVID-19, and none of the CE species were correlated with PCSK9 in patients with severe COVID-19. Levels of all CE species negatively correlated with C-reactive protein in severe COVID-19 patients. Notably, FC was induced in severe compared to moderate COVID-19. The FC/CE ratio correlated positively with inflammatory markers and was associated with non-survival. The current study suggests that the imbalance between CE and FC levels is associated with disease severity and mortality in patients with COVID-19. [ABSTRACT FROM AUTHOR]

Infectious diseases are associated with low iron levels and the induction of hepcidin, the primary protein regulating cellular iron export. Bone morphogenetic protein 6 (BMP6), a key regulator of hepcidin expression, has not yet been analyzed in the plasma of patients with systemic inflammatory response syndrome (SIRS) or sepsis. An analysis of 38 SIRS, 39 sepsis, and 78 septic shock patients revealed similar levels of BMP6 in sepsis and septic shock, which were lower compared to patients with SIRS and healthy controls. Plasma BMP6 levels did not correlate with procalcitonin and C-reactive protein levels in patients with SIRS or sepsis/septic shock. Neither bacterial nor SARS-CoV-2 infections affected plasma BMP6 levels. There was no difference in BMP6 levels between ventilated and non-ventilated patients, or between patients with and without dialysis. Vasopressor therapy did not alter BMP6 levels. Survivors had plasma BMP6 levels similar to non-survivors. Due to the high variability of plasma BMP6 levels, these analyses have limited clinical relevance. Iron, ferritin, and transferrin levels were known in at least 50% of patients but did not correlate with plasma BMP6 levels. In conclusion, this study showed normal BMP6 plasma levels in SIRS, which are reduced in patients with sepsis and septic shock. This suggests that the commonly observed increase in hepcidin levels and the decline in iron levels in SIRS, sepsis, and septic shock are not due to higher BMP6. [ABSTRACT FROM AUTHOR]

Neutrophils are critical immune cells in severe coronavirus disease 2019 (COVID-19). S100 calcium-binding protein A12 (S100A12) is highly expressed in neutrophils during acute inflammation. The aim of this study was to evaluate serum S100A12 levels as a diagnostic and prognostic tool in COVID-19. Serum samples of patients with moderate and severe COVID-19 were collected during 2020 to 2024. Enzyme-linked immunosorbent assay was used to measure serum S100A12 levels in 63 patients with moderate COVID-19, 60 patients with severe disease and 33 healthy controls. Serum S100A12 levels were elevated in moderate COVID-19 compared to controls and were even higher in severe cases. In moderate disease, serum S100A12 levels positively correlated with immune cell counts. While C-reactive protein and procalcitonin are established inflammation markers, they did not correlate with serum S100A12 levels in either patient cohort. Patients with severe COVID-19 and vancomycin-resistant enterococcus (VRE) infection had increased S100A12 levels. Elevated S100A12 levels were also observed in patients with herpes simplex reactivation. Fungal superinfections did not alter S100A12 levels. These data show that serum S100A12 increases in moderate and severe COVID-19 and is further elevated by VRE bloodstream infection and herpes simplex reactivation. Therefore, S100A12 may serve as a novel biomarker for severe COVID-19 and an early diagnostic indicator for bacterial and viral infections. [ABSTRACT FROM AUTHOR]

Primary sclerosing cholangitis (PSC) is a serious liver disease associated with inflammatory bowel disease (IBD). Galectin-3, an inflammatory and fibrotic molecule, has elevated circulating levels in patients with chronic liver disease and inflammatory bowel disease (IBD). This study aims to clarify whether galectin-3 can differentiate between patients with IBD, PSC, and PSC-IBD. Our study measured serum galectin-3 levels in 38 healthy controls, 55 patients with IBD, and 22 patients with PSC (11 patients had underlying IBD and 11 patients did not), alongside the urinary galectin-3 of these patients and 18 controls. Serum and urinary galectin-3 levels in IBD patients were comparable to those in controls. Among IBD patients, those with high fecal calprotectin, indicating severe disease, exhibited lower serum and elevated urinary galectin-3 levels compared to those with low calprotectin levels. Serum galectin-3 levels were inversely correlated with C-reactive protein levels. PSC patients displayed higher serum and urinary galectin-3 levels than IBD patients, with the highest serum levels observed in PSC patients with coexisting IBD. There was no correlation between serum and urinary galectin-3 levels and laboratory indicators of liver injury in both IBD and PSC patients. In conclusion, this study demonstrates that serum and urinary galectin-3 levels can distinguish IBD from PSC patients, and also reveals higher serum galectin-3 levels in PSC-IBD patients compared to those with isolated PSC. [ABSTRACT FROM AUTHOR]