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.)

Iron Dyshomeostasis in COVID-19: Biomarkers Reveal a Functional Link to 5-Lipoxygenase Activation.

Coronavirus disease 2019 (COVID-19) is characterized by a broad spectrum of clinical symptoms. After acute infection, some subjects develop a post-COVID-19 syndrome known as long-COVID. This study aims to recognize the molecular and functional mechanisms that occur in COVID-19 and long-COVID patients and identify useful biomarkers for the management of patients with COVID-19 and long-COVID. Here, we profiled the response to COVID-19 by performing a proteomic analysis of lymphocytes isolated from patients. We identified significant changes in proteins involved in iron metabolism using different biochemical analyses, considering ceruloplasmin (Cp), transferrin (Tf), hemopexin (HPX), lipocalin 2 (LCN2), and superoxide dismutase 1 (SOD1). Moreover, our results show an activation of 5-lipoxygenase (5-LOX) in COVID-19 and in long-COVID possibly through an iron-dependent post-translational mechanism. Furthermore, this work defines leukotriene B4 (LTB4) and lipocalin 2 (LCN2) as possible markers of COVID-19 and long-COVID and suggests novel opportunities for prevention and treatment.

Identification of Neutrophil-Related Factor LCN2 for Predicting Severity of Patients With Influenza A Virus and SARS-CoV-2 Infection.

Background: Influenza and COVID-19 are respiratory infectious diseases that are characterized by high contagiousness and high mutation and pose a serious threat to global health. After Influenza A virus (IAV) and SARS-CoV-2 infection, severe cases may develop into acute lung injury. Immune factors act as an important role during infection and inflammation. However, the molecular immune mechanisms still remain unclear. We aimed to explore immune-related host factors and core biomarker for severe infection, to provide a new therapeutic target of host factor in patients. Methods: Gene expression profiles were obtained from Gene Expression Omnibus and the Seurat R package was used for data process of single-cell transcriptome. Differentially expressed gene analysis and cell cluster were used to explore core host genes and source cells of genes. We performed Gene Ontology enrichment, Kyoto Encyclopedia of Genes and Genomes analysis, and gene set enrichment analysis to explore potential biological functions of genes. Gene set variation analysis was used to evaluate the important gene set variation score for different samples. We conduct Enzyme-linked immunosorbent assay (ELISA) to test plasma concentrations of Lipocalin 2 (LCN2). Results: Multiple virus-related, cytokine-related, and chemokine-related pathways involved in process of IAV infection and inflammatory response mainly derive from macrophages and neutrophils. LCN2 mainly in neutrophils was significantly upregulated after either IAV or SARS-CoV-2 infection and positively correlated with disease severity. The plasma LCN2 of influenza patients were elevated significantly compared with healthy controls by ELISA and positively correlated with disease severity of influenza patients. Further bioinformatics analysis revealed that LCN2 involved in functions of neutrophils, including neutrophil degranulation, neutrophil activation involved in immune response, and neutrophil extracellular trap formation. Conclusion: The neutrophil-related LCN2 could be a promising biomarker for predicting severity of patients with IAV and SARS-CoV-2 infection and may as a new treatment target in severe patients.

Lipocalin-2, S100A8/A9, and cystatin C: Potential predictive biomarkers of cardiovascular complications in COVID-19.

Severe coronavirus (SARS-COV-2) infection often leads to systemic inflammation accompanied by cardiovascular complications including venous thromboembolism (VTE). However, it is largely undefined if inflammatory markers such as lipocalin-2 (LNC2), calprotectin (S100A8/A9), and cystatin C (CST3), previously linked with VTE, play roles in cardiovascular complications and advancement of COVID-19 severity. To investigate the same, hospitalized moderate and severe (presented pneumonia and required intensive care) COVID-19 patients were recruited. The levels of plasma LNC2, S100A8/A9, CST3, myoglobin, and cardiac Troponin I (cTnI) were assessed through enzyme-linked immunosorbent assay (ELISA). The investigation revealed a significantly upregulated level of plasma LNC2 at the moderate stage of SARS-CoV-2 infection. In contrast, the levels of S100A8/A9 and CST3 in moderate patients were comparable to healthy controls; however, a profound induction was observed only in severe COVID-19 patients. The tissue injury marker myoglobin was unchanged in moderate patients; however, a significantly elevated level was observed in the critically ill COVID-19 patients. In contrast, cTnI level was unchanged both in moderate and severe patients. Analysis revealed a positive correlation between the levels of S100A8/A9 and CST3 with myoglobin in COVID-19. In silico analysis predicted interactions of S100A8/A9 with toll-like receptor 4 (TLR-4), MyD88 LY96, and LCN2 with several other inflammatory mediators including MMP2, MMP9, TIMP1, and interleukins (IL-6, IL-17A, and IL-10). In summary, early induction of LCN2 likely plays a role in advancing the COVID-19 severity. A positive correlation of S100A8/A9 and CST3 with myoglobin suggests that these proteins may serve as predictive biomarkers for thromboembolism and tissue injury in COVID-19.