Serum Clusterin Concentration and Its Glycosylation Changes as Potential New Diagnostic Markers of SARS-CoV-2 Infection and Recovery Process.

COVID-19 is an infectious disease caused by the SARS-CoV-2 virus. Glycoprotein clusterin (CLU) has many functions such as phagocyte recruitment, complement system inhibition, apoptosis inhibition, hormone and lipid transport, as well as in the immune response. The study aimed to assess the changes in CLU concentrations and the profile and degree of CLU glycosylation between patients with severe COVID-19, convalescents, and healthy subjects (control). The profile and degree of serum CLU N-glycosylation were analyzed using lectin-ELISA with specific lectins. CLU concentrations were significantly lower and relative reactivities of CLU glycans with SNA (Sambucus nigra agglutinin) were significantly higher in severe COVID-19 patients in comparison to convalescents and the control group. The relative reactivities of CLU glycans with MAA (Maackia amurensis agglutinin), together with relative reactivity with LCA (Lens culinaris agglutinin), were also significantly higher in patients with severe COVID-19 than in convalescents and the control group, but they also significantly differed between convalescents and control. The development of acute inflammation in the course of severe COVID-19 is associated with a decrease in CLU concentration, accompanied by an increase in the expression of α2,3-linked sialic acid, and core fucose. Both of these parameters can be included as useful glycomarkers differentiating patients with severe COVID-19 from convalescents and the control group, as well as convalescents and healthy subjects.

Inflammatory cell-associated tumors. Not only macrophages (TAMs), fibroblasts (TAFs) and neutrophils (TANs) can infiltrate the tumor microenvironment. The unique role of tumor associated platelets (TAPs).

It is well known that various inflammatory cells infiltrate cancer cells. Next to TAMs (tumor-associated macrophages), TAFs (tumor-associated fibroblasts) and TANs (tumor-associated neutrophils) also platelets form the tumor microenvironment. Taking into account the role of platelets in the development of cancer, we have decided to introduce a new term: tumor associated platelets-TAPs. To the best of our knowledge, thus far this terminology has not been employed by anyone. Platelets are the first to appear at the site of the inflammatory process that accompanies cancer development. Within the first few hours from the start of the colonization of cancer cells platelet-tumor aggregates are responsible for neutrophils recruitment, and further release a number of factors associated with tumor growth, metastasis and neoangiogenesis. On the other hand, it also has been indicated that factors delivered from platelets can induce a cytotoxic effect on the proliferating neoplastic cells, and even enhance apoptosis. Undoubtedly, TAPs' role seems to be more complex when compared to tumor associated neutrophils and macrophages, which do not allow for their division into TAP P1 and TAP P2, as in the case of TANs and TAMs. In this review we discuss the role of TAPs as an important element of tumor invasiveness and as a potentially new therapeutic target to prevent cancer development. Nevertheless, better exploring the interactions between platelets and tumor cells could help in the formulation of new therapeutic goals that support or improve the effectiveness of cancer treatment.

Diagnostic utility of protein to creatinine ratio (P/C ratio) in spot urine sample within routine clinical practice.

The spot (random) urine protein to creatinine ratio (P/C ratio) is an alternative, fast and simple method of detecting and estimating the quantitative assessment of proteinuria. The aim of the work was to review the literature concerning the usefulness of spot urine P/C ratio evaluation in the diagnosis of proteinuria in the course of kidney disease, hypertension, gestational hypertension, preeclampsia, immunological diseases, diabetes mellitus, and multiple myeloma, and in the diagnosis of proteinuria in children. We searched the PubMed and Google Scholar databases using the following keywords: proteinuria, spot urine protein to creatinine ratio, spot urine P/C ratio, protein creatinine index, PCR (protein to creatinine ratio), P/C ratio and methods, Jaffe versus enzymatic creatinine methods, urine protein methods, spot urine protein to creatinine ratio versus ACR (albumin to creatinine ratio), proteinuria versus albuminuria, limitations of the P/C ratio. More weight was given to the articles published in the last 10-20 years. A spot urine P/C ratio >20 mg/mmol (0.2 mg/mg) is the most commonly reported cutoff value for detecting proteinuria, while a P/C ratio value >350 mg/mmol (3.5 mg/mg) confirms nephrotic proteinuria. The International Society for the Study of Hypertension in Pregnancy recommends a P/C ratio of 30 mg/mmol (0.3 mg/mg) for the classification of proteinuria in pregnant women at risk of preeclampsia. A high degree of correlation was observed between P/C ratio values and the protein concentration in 24-h urine collections. The spot urine P/C ratio is a quick and reliable test that can eliminate the need for a daily 24-h urine collection. However, in doubtful situations, it is still recommended to assess proteinuria in a 24-h urine collection. The literature review indicates the usefulness of the spot P/C ratio in various disease states; therefore, this test should be available in every laboratory. However, the challenge for the primary care physician is to know the limitations of the methods used to determine the protein and creatinine concentrations that are used to calculate the P/C ratio. Moreover, the P/C ratio cutoff used should be determined in individual laboratories because it depends on the patient population and the laboratory methodologies.

Intraoperative Peritoneal Interleukin-6 Concentration Changes in Relation to the High-Mobility Group Protein B1 and Heat Shock Protein 70 Levels in Children Undergoing Cholecystectomy.

The aim was the evaluation of IL-6 concentration in peritoneal lavage fluid of children which underwent cholecystectomy to ascertain if there is a difference in early inflammatory response depending on the type of surgical approach (open vs. laparoscopy). The analysis of high-mobility group protein B1 (HMGB1) and heat shock protein 70 (HSP70) was performed to find out if the source of IL-6 was related to tissue damage. IL-6 concentration in peritoneal lavage fluid samples, obtained at the beginning and at the end of the laparoscopic (N = 23) and open cholecystectomy (N = 14), was tested with a routinely used electrochemiluminescence assay. The concentrations of HMGB1 and HSP70 were analyzed with the use of an ELISA method. Statistical analysis was performed using the STATISTICA PL release 12.5 Program. The differences were assessed using the Mann-Whitney U test and Wilcoxon matched pairs test. Correlations were studied by using the Spearman correlation test. Our results demonstrated significant peritoneal lavage fluid IL-6 concentration growth measured at the end of the cholecystectomy as compared to the beginning, regardless of the type of the procedure. IL-6 growth during open cholecystectomy was greater compared to laparoscopic cholecystectomy (62.51-fold vs. 3.19-fold). IL-6 concentration did not correlate with HMGB1 and HSP70, which indicate that the significant growth of this cytokine was not related to mechanical tissue damage due to surgical procedure. A clinical significance of the study could be related to the fact that the evaluation of IL-6 concentration in peritoneal lavage fluid may be useful to assess an early local inflammatory response.

Serum and cerebrospinal fluid Neudesin concentration and Neudesin Quotient as potential circulating biomarkers of a primary brain tumor.

BACKGROUND: Despite the previously suggested role of Neudesin in tumorigenesis and its potential as a novel target for the treatment of cancers, its prognostic value has never been examined. Thus, the aim of the study was to evaluate Neudesin concentrations in primary brain tumor patients and make a comparison with non-tumoral individuals. METHODS: Cerebrospinal fluid (CSF) and serum Neudesin concentration was evaluated by means of the ELISA method. RESULTS: The total group of brain tumor patients had statistically lower serum Neudesin concentrations compared to the non-tumoral group (P = 0.037). The meningeal tumor subgroup also had statistically lower serum Neudesin concentrations compared to the non-tumoral group (P = 0.012). The Astrocytic brain tumor subgroup had significantly higher CSF Neudesin concentrations compared to the non-tumoral group (P = 0.046). Neudesin Quotient (CSF concentration divided by serum concentration) in the astrocytic brain tumor subgroup was statistically higher compared to the non-tumoral group (P = 0.023). Males had statistically lower concentrations of the serum Neudesin compared to females (P = 0.047). Univariate linear regression analysis revealed that for women the serum Neudesin concentration was 1.53 times higher than for men. In the model of multivariate linear regression analysis, predictor variables influencing serum Neudesin concentrations included CSF Neudesin concentration and the Neudesin Quotient, if other model parameters are fixed. The developed model explains 82% of the variance in serum Neudesin concentration. Both linear regression models, univariate and multivariate, pointed to fewer factors with a potential to influence the Neudesin Quotient compared to serum Neudesin concentration. CONCLUSIONS: In astrocytic brain tumor patients Neudesin concentrations within the cerebrospinal fluid are higher compared with non-tumoral individuals. Serum Neudesin concentration strongly correlates with its CSF level. In primary brain tumor patients serum Neudesin concentration is clearly gender-dependent. Linear regression models pointed to fewer factors that may influence the Neudesin Quotient value, which suggests it is a better biomarker of astrocytic brain tumors than serum and CSF Neudesin concentrations alone.

Mean Platelet Volume (MPV): New Perspectives for an Old Marker in the Course and Prognosis of Inflammatory Conditions.

Platelet size has been demonstrated to reflect platelet activity and seems to be a useful predictive and prognostic biomarker of cardiovascular events. It is associated with a variety of prothrombotic and proinflammatory diseases. The aim is a review of literature reports concerning changes in the mean platelet volume (MPV) and its possible role as a biomarker in inflammatory processes and neoplastic diseases. PubMed database was searched for sources using the following keywords: platelet activation, platelet count, mean platelet volume and: inflammation, cancer/tumor, cardiovascular diseases, myocardial infarction, diabetes, lupus disease, rheumatoid arthritis, tuberculosis, ulcerative colitis, renal disease, pulmonary disease, influencing factors, age, gender, genetic factors, oral contraceptives, smoking, lifestyle, methods, standardization, and hematological analyzer. Preference was given to the sources which were published within the past 20 years. Increased MPV was observed in cardiovascular diseases, cerebral stroke, respiratory diseases, chronic renal failure, intestine diseases, rheumatoid diseases, diabetes, and various cancers. Decreased MPV was noted in tuberculosis during disease exacerbation, ulcerative colitis, SLE in adult, and different neoplastic diseases. The study of MPV can provide important information on the course and prognosis in many inflammatory conditions. Therefore, from the clinical point of view, it would be interesting to establish an MPV cut-off value indicating the intensity of inflammatory process, presence of the disease, increased risk of disease development, increased risk of thrombotic complications, increased risk of death, and patient's response on applied treatment. Nevertheless, this aspect of MPV evaluation allowing its use in clinical practice is limited and requires further studies.

Lectin adhesion proteins (P-, L- and E-selectins) as biomarkers in colorectal cancer.

CONTEXT: Selectins probably participate in the interactions between platelets and other inflammatory cells in cancer invasion and metastasis formation. We assessed a potential relationship of P-, L- and E-selectin in colorectal cancer (CRC) patients in relation to tumour advancement according to TNM classification, and tumour location. MATERIALS AND METHODS: The study group was composed of 53 CRC patients and 25 healthy subjects. Plasma levels of soluble P-, L- and E-selectins were measured using the immunoenzymatic method with Quantikine kits (R&D Systems, Minneapolis, MN). RESULTS: The mean levels of all selectins were significantly higher in CRC patients compared to healthy controls. The highest level of sP-selectin was observed in patients with metastases to the liver (stage IV), and was significantly higher than in patients without metastases (stage I/II) and with lymph node metastases (stage III), p = .02. The highest levels of sL- and sE-selectin were observed in patients with lymph node metastasis. We also found sP-selectin to be the best predictor of CRC. CONCLUSION: Our finding show possible involvement of tested selectins in CRC advancement and forming metastasis. Among sL- and E- selectins, P-selectin plays an important role in the progression of CRC and could be an attractive biomarker with clinical significance.

The Effect of Nonsurgical Periodontal Therapy on the Level of Human Neutrophil Peptides 1-3 in Patients with Aggressive Periodontitis.

PURPOSE: To assess the presence of HNP1-3 in the gingival crevicular fluid (GCF) of patients suffering from aggressive periodontitis before and after nonsurgical periodontal therapy. MATERIALS AND METHODS: Twenty patients, each with generalised aggressive periodontitis (GAP) were included in the study. After periodontal examination, one site with a probing depth (PD) ≥ 4 mm was selected. Patients received nonsurgical treatment (scaling and root planing [SRP]) with additional administration of systemic antibiotic therapy (amoxicillin 375 mg three times daily + metronidazole 250 mg three times daily for 7 days). Prior to therapy and 3 and 6 months after, the following parameters were evaluated from the same site: PD, gingival recession (GR), clinical attachment level (CAL), plaque index (PI), bleeding on probing (BOP), sulcus fluid flow rate (SFFR). The level of HNP1-3 in GCF was determined by means of a commercially available ELISA kit. RESULTS: Compared to baseline, the level of HNP 1-3 did not show statistically significant differences at 3 and 6 months. The evaluated clinical parameters and SFFR showed statistically significant decreases compared to baseline. At 6 months, PD (median) decreased from 7 to 3.5 and CAL (median) decreased from 7 to 4. CONCLUSION: In patients with GAP, nonsurgical periodontal therapy in conjunction with systemic administration of amoxicillin and metronidazole had no effect on the level of HNP1-3 in GCF.

Plasma C16-Cer levels are increased in patients with preterm labor.

INTRODUCTION: The pathogenesis of preterm labor is fragmentarily explained. The most widely accepted theory points out to infection and inflammation as possible causes, which can be mediated by potentially different factors, including sphingolipid mediators. Sphingolipids are a class of lipids that have been shown as important mediators in various cell processes such as: proliferation, growth, apoptosis, stress response, necrosis and inflammation. The aim of the study was to assess plasma concentrations of selected sphingolipids in patients with preterm labor. MATERIAL AND METHODS: We used ultra-high performance liquid chromatography with triple mass spectrometry (UHPLC-ESI-MS/MS) to assess plasma concentrations of the 11 sphingolipids in patients presenting with symptoms of preterm labor (n=61) and threatened preterm labor (n=40). RESULTS: We observed a statistically significant increase (p-value<0.004) in plasma concentrations of C16-Cer in patients with preterm labor as compared to the control group. We also found C16-Cer to be the best predictor of preterm labor in the group of patients with symptoms occurring after 32 weeks of gestation. CONCLUSIONS: Our findings show a possible involvement of selected sphingolipids, especially C16-Cer, in the pathogenesis of preterm labor. Their role as predictors of preterm delivery needs to be validated in the future on larger group of patients.

Application of the Bead-Based Technique in Neurodegeneration: A Literature Review.

BACKGROUND: Alzheimer's disease (AD) is the most common disease causing neurodegeneration. The lower concentration of ß-amyloid 1-42 (Aß1-42) together with increased levels of total tau protein (T-tau) and phosphorylated tau protein (P-tau) in the cerebrospinal fluid (CSF) make a panel of well-established biomarkers in AD diagnosis. Addition of novel biomarkers to the gold standard biomarker panel might improve the diagnostic accuracy of neurodegeneration. This goal might be reached by the use of multiplexing, which is a simultaneous measurement of multiple analytes in a single sample volume and within a single cycle or run. OBJECTIVE/METHODS: Therefore the aim of the current review was to present, according to our best knowledge, available data concerning the evaluation of concentrations and diagnostic accuracy of well-established biomarkers in AD as well as novel biomarkers analyzed with the use of the bead-based technique. Additionally we discuss the utilization of the bead-based technique as compared to the conventional ELISA method. RESULTS: Literature data indicate that the bead-based technique revealed diagnostic sensitivity, specificity and coefficients of variation at the levels similar to ELISA. Moreover, an addition of novel biomarkers (tested by means of the bead-based technique) to the gold standard biomarker panel improved the diagnostic accuracy of neurodegeneration. CONCLUSION: Review of literature data shows that the combined analysis of classical CSF biomarkers with novel biomarkers might increase the specificity and sensitivity of performed tests. However, we concluded that the replacement of conventional ELISA with the bead-based technique requires new reference intervals for Aß1-42, T-tau and P-tau concentrations.

[Procalcitonin (PCT), contemporary indicator of infection and inflammation]. / Prokalcytonina (PCT), wspólczesny wskaznik infekcji i stanów zapalnych.

Procalcitonin is a protein synthesized during sepsis and inflammation. In these states, its production is stimulated by inflammatory mediators and bacterial toxins. Routine determination of PCT concentration is useful in the rapid detection and monitoring of bacterial and fungal infections. The article presents the latest meta-analysis and clinical reports on the use of the PCT and comparison of its diagnostic sensitivity and specificity with other indicators of inflammation and infection in both neonates and in the adult population. Synthesis, properties and metabolism of PCT and the available methods and conditions of the determination are discussed. Presented data indicate a high sensitivity and specificity of PCT determinations, especially in bacterial infection and, what is very important, short duration of the assay and the use of a small sample volume. Assess the dynamics of changes in the concentrations of PCT can provide information not only about the course of infection but also facilitates the decision to introduce and then to discontinue antibiotic therapy.

Multifunctional CD40L: pro- and anti-neoplastic activity.

The CD40 ligand is a type I transmembrane protein that belongs to a tumor necrosis factor (TNF) superfamily. It is present not only on the surface of activated CD4+ T cells, B cells, blood platelets, monocytes, and natural killer (NK) cells but also on cancer cells. The receptor for ligand is constitutively expressed on cells, TNF family protein: CD40. The role of the CD40/CD40L pathway in the induction of body immunity, in inflammation, or in hemostasis has been well documented, whereas its involvement in neoplastic disease is still under investigation. CD40L ligand may potentiate apoptosis of tumor cells by activation of nuclear factor-κB (NF-κB), AP-1, CD95, or caspase-depended pathways and stimulate host immunity to defend against cancer. Although CD40L has a major contribution to anti-cancer activity, many reports point at its ambivalent nature. CD40L enhance release of strongly pro-angiogenic factor, vascular endothelial growth factor (VEGF), and activator of coagulation, TF, the level of which is correlated with tumor metastasis. CD40L involvement in the inhibition of tumor progression has led to the emergence of not only therapy using recombinant forms of the ligand and vaccines in the treatment of cancer but also therapy consisting of inhibiting platelets-main source of CD40L. This article is a review of studies on the ambivalent role of CD40L in neoplastic diseases.

Are Changes in Serum IgG Glycosylation Related to the Severe Course of SARS-CoV-2 Infection and Recovery Process? In Search of New Diagnostic and Prognostic Biomarkers.

Introduction: Immunoglobulin G (IgG) glycosylation affects its effector functions and is essential in many steps of the inflammatory cascade. Therefore, it may be an important parameter for assessing the body's immune response during the course of COVID-19 (Coronavirus disease 2019). Methods: The N- and O-glycosylation of serum IgG in severe COVID-19 patients (n=87), convalescents (n=50), and healthy subjects (n=65) were examined using a modified lectin-ELISA method with specific biotinylated lectins. The obtained data were analyzed using STATISTICA 13.3PL software. Results: We showed significantly higher expression of Lewisx oligosaccharide structures in severe COVID-19 patients than in the other two groups. Moreover, significantly lower expression of Lewisy sugar structures in IgG glycans was observed in the convalescents when compared with COVID-19 patients and healthy subjects. The lowest expression of highly branched N-glycans in cases of severe COVID-19 indicates that the development of the disease is associated with the presence of typical IgG biantennary N-glycans. The lack of significant differences in the expression of Tn antigen in IgG between studied groups and the significantly lower expression of T antigen in convalescents compared to the patients with severe COVID-19 and healthy subjects indicates a decrease in the content of the T antigen in IgG O-glycans in subjects recovered from COVID-19. Substantially higher reactivities of IgG O-glycans with Jacalin observed in COVID-19 patients and convalescents in comparison to the control group were most probably caused by increased expression of core 3 O-glycans in IgG. Conclusion: Severe COVID-19 is accompanied by the expression in serum IgG of sialylated biantennary and highly branched N-glycans, decorated by fucose of Lewisx and Lewisy structures. The higher reactivity of IgG O-glycans with Jacalin in severe COVID-19 patients and convalescents indicates that the disease development and the recovery process are most probably accompanied by increased expression of the core 3 O-glycans.

Redox Biomarkers - An Effective Tool for Diagnosing COVID-19 Patients and Convalescents.

Aim: COVID-19 triggers the overproduction of reactive oxygen species (ROS) which, in combination with a weakened antioxidant barrier, can lead to protein oxidation and lipid peroxidation. The aim of this study was to evaluate enzymatic and non-enzymatic antioxidants, the overall redox potential, and protein and lipid peroxidation products in COVID-19 patients, convalescents, and healthy subjects, and to the determine the diagnostic applicability of these parameters in COVID-19 patients. Materials and Methods: The study involved 218 patients with COVID-19, 69 convalescents, and 48 healthy subjects who were selected for the research based on age and sex. The study was conducted between 20 February 2021 and 20 November 2021 in Bialystok, Poland. The antioxidant barrier, redox status, and oxidative damage products were assessed in serum/plasma samples with the use of colorimetric and spectrophotometric assays. Results: Glutathione reductase (GR) activity was higher, whereas total antioxidant capacity (TAC) was lower in COVID-19 patients than in convalescents (p<0.0001) and the control group (p<0.0001). The concentrations of advanced glycation end products (AGEs), advanced oxidation protein products (AOPP), 4-hydroxynonenal (4-HNE), and malondialdehyde (MDA) were higher in COVID-19 patients (p<0.0001) and convalescents (p<0.0001) than in the control group. AGEs were the most effective diagnostic biomarker for differentiating COVID-19 patients from the control group (AUC=0.9971) and convalescents from the control group (AUC=1.000). Conclusion: An infection with the SARS-CoV-2 disrupts the redox balance and increases protein oxidation and lipid peroxidation. AGEs fulfill the criteria for a potential diagnostic biomarker in COVID-19 patients and convalescents.

Fashionable, but What is Their Real Clinical Usefulness? NLR, LMR, and PLR as a Promising Indicator in Colorectal Cancer Prognosis: A Systematic Review.

The link between inflammation and cancer is still an attractive subject of many studies because systemic inflammatory response has been proven to play a pivotal role in cancer progression and metastasis. The strongest relationship between chronic inflammation and cancer development is observed in colorectal cancer (CRC). The evaluation of ratios derived from the routinely performed inflammatory biomarkers shows limited performances and limited clinical utility when individually used as prognostic factors for patients with CRC. In this review, we would like to summarize the latest knowledge about the diagnostic utility of systemic inflammatory ratios: neutrophil/lymphocyte (NLR), lymphocyte/monocyte (LMR), and platelet/lymphocyte (PLR) in CRC. We focused on the papers that assessed the diagnostic utility of blood cell parameters on the basis of the area under the ROC curve published in the recent 6 years. Identification of biomarkers that are significantly associated with prognostic in cancer would help the selection of patients with a high risk of poor outcomes.

Clinical Significance and Diagnostic Utility of NLR, LMR, PLR and SII in the Course of COVID-19: A Literature Review.

Nowadays, society is increasingly struggling with infectious diseases that are characterized by severe course and even death. Recently, the whole world has faced the greatest epidemiological threat, which is COVID-19 caused by SARS CoV-2 virus. SARS CoV-2 infection is often accompanied by severe inflammation, which can lead to the development of different complications. Consequently, clinicians need easily interpreted and effective markers of inflammation that can predict the efficacy of the treatment and patient prognosis. Inflammation is associated with changes in many biochemical and hematological parameters, including leukocyte counts and their populations. In COVID-19, changes in leukocytes count populations such as neutrophils, lymphocytes or monocytes are observed. The numerous research confirm that indicators like neutrophil-to-lymphocyte ratio (NLR), lymphocyte-to-monocyte ratio (LMR), platelets-to-lymphocyte ratio (PLR) and systemic inflammatory index (SII) may prove effective in assessment patient prognosis and choosing optimal therapy. Therefore, in this review, we would like to summarize the latest knowledge about the diagnostic utility of systemic inflammatory ratios - NLR, LMR, PLR and SII in patients with COVID-19. We focused on the papers evaluating the diagnostic utility of inflammatory ratios using ROC curve published in the recent 3 years. Identification of biomarkers associated with inflammation would help the selection of patients with severe course of COVID-19 and high risk of death.

Neutrophil/Lymphocyte Ratio (NLR) and Lymphocyte/Monocyte Ratio (LMR) - Risk of Death Inflammatory Biomarkers in Patients with COVID-19.

Aim: The aim of our retrospective study was search for new prognostic parameters, which can help quickly and cheaply identify patients with risk for severe course of SARS-CoV-2 infection. Materials and Methods: The following peripheral blood combination biomarkers were calculated: NLR (neutrophil/lymphocytes ratio), LMR (lymphocyte/monocyte ratio), PLR (platelet/lymphocyte ratio), dNLR (neutrophils/(white blood cells - neutrophils)), NLPR (neutrophil/(lymphocyte × platelet ratio)) in 374 patients who were admitted to the Temporary Hospital no 2 of Clinical Hospital in Bialystok (Poland) with COVID-19. The patients were divided into four groups depending on the severity of the course of COVID-19 using MEWS classification. Results: The NLR and dNLR were significantly increased with the severity of COVID-19, according to MEWS score. The AUC for the assessed parameters was higher in predicting death in patients with COVID-19: NLR (0.656, p=0.0018, cut-off=6.22), dNLR (0.615, p=0.02, cut-off=3.52) and LMR (0.609, p=0.03, cut-off=2.06). Multivariate COX regression analysis showed that NLR median above 5.56 (OR: 1.050, P=0.002), LMR median below 2.23 (OR: 1.021, P=0.011), and age >75 years old (OR: 1.072, P=0.000) had a significant association with high risk of death during COVID-19. Conclusion: Our results indicate that NLR, dNLR, and LMR calculated on admission to the hospital can quickly and easy identify patients with risk of a more severe course of COVID-19. Increase NLR and decrease LMR have a significant predictive value in COVID-19 patient's mortality and might be a potential biomarker for predicting death in COVID-19 patients.

The Diagnostic Value of Inflammatory Markers (CRP, IL6, CRP/IL6, CRP/L, LCR) for Assessing the Severity of COVID-19 Symptoms Based on the MEWS and Predicting the Risk of Mortality.

Introduction: Various diagnostic tools are used to assess the severity of COVID-19 symptoms and the risk of mortality, including laboratory tests and scoring indices such as the Modified Early Warning Score (MEWS). The diagnostic value of inflammatory markers for assessing patients with different severity of COVID-19 symptoms according to the MEWS was evaluated in this study. Materials and Methods: The concentrations of CRP (C-reactive protein) (immunoassay) and IL6 (interleukin 6) (electrochemiluminescence assay) were determined, and CRP/IL6, CRP/L, and LCR ratios were calculated in blood serum samples collected from 374 COVID-19 patients. Results: We demonstrated that CRP, IL6, CRP/IL6, CRP/L, LCR inflammatory markers increase significantly with disease progression assessed based on the MEWS in COVID-19 patients and may be used to differentiating patients with severe and non-severe COVID-19 and to assess the mortality. Conclusion: The diagnostic value of inflammatory markers for assessing the risk of mortality and differentiating between patients with mild and severe COVID-19 was confirmed.

Changes in chemokine and growth factor levels may be useful biomarkers for monitoring disease severity in COVID-19 patients; a pilot study.

Aim: The aim of the present study was to assess differences in the serum levels of chemokines and growth factors (GFs) between COVID-19 patients and healthy controls. The diagnostic utility of the analyzed proteins for monitoring the severity of the SARS-CoV- 2 infection based on the patients' MEWS scores was also assessed. Materials and methods: The serum levels of chemokines and growth factors were analyzed in hospitalized COVID-19 patients (50 women, 50 men) with the use of the Bio-Plex Pro™ Human Cytokine Screening Panel (Biorad) and the Bio-Plex Multiplex system. Results: The study demonstrated that serum levels of MIP-1α, RANTES, Eotaxin, CTACK, GRO-α, IP-10, MIG, basic-FGF, HGF, SCGF-ß, G-CSF, M-CSF, SCF, MIF, LIF, and TRAIL were significant higher in COVID-19 patients than in the control group. The concentrations of CTACK, GRO-α, IP-10, MIG, basic-FGF, HGF, PDGF- BB, GM-CSF, SCF, LIF, and TRAIL were higher in asymptomatic/mildly symptomatic COVID-19 patients (stage 1) and COVID-19 patients with pneumonia without respiratory failure (stage 2). The receiver operating characteristic (ROC) analysis revealed that IP-10, MIF, MIG, and basic-FGF differentiated patients with COVID-19 from healthy controls with the highest sensitivity and specificity, whereas GM-CSF, basic-FGF, and MIG differentiated asymptomatic/mildly symptomatic COVID-19 patients (stage 1) from COVID-19 patients with pneumonia without respiratory failure (stage 2) with the highest sensitivity and specificity. Conclusions: MIG, basic-FGF, and GM-CSF can be useful biomarkers for monitoring disease severity in patients with COVID-19.

Unveiling COVID-19 Secrets: Harnessing Cytokines as Powerful Biomarkers for Diagnosis and Predicting Severity.

Introduction: In coronavirus disease (COVID-19), inflammation takes center stage, with a cascade of cytokines released, contributing to both inflammation and lung damage. The objective of this study is to identify biomarkers for diagnosing and predicting the severity of COVID-19. Materials and Methods: Cytokine levels were determined in the serum from venous blood samples collected from 100 patients with COVID-19 and 50 healthy controls. COVID-19 patients classified based on the Modified Early Warning (MEWS) score. Cytokine concentrations were determined with a multiplex ELISA kit (Bio-Plex Pro™ Human Cytokine Screening Panel). Results: The concentrations of all analyzed cytokines were elevated in the serum of COVID-19 patients relative to the control group, but no significant differences were observed in interleukin-9 (IL-9) and IL-12 p70 levels. In addition, the concentrations of IL-1α, IL-1ß, IL-1ra, IL-2Rα, IL-6, IL-12 p40, IL-18, and tumor necrosis factor alpha (TNFα) were significantly higher in symptomatic patients with accompanying pneumonia without respiratory failure (stage 2) than in asymptomatic/mildly symptomatic patients (stage 1). Conclusion: The study revealed that IL-1ra, IL-2Rα, IL-6, IL-8, IL-12 p40, IL-16, and IL-18 levels serve as potential diagnostic biomarkers in COVID-19 patients. Furthermore, elevated IL-1α levels proved to be valuable in assessing the severity of COVID-19.