scholarly journals Neutrophil extracellular traps: diagnostic and prognostic value in COVID-19

2020 ◽  
Vol 48 ◽  
pp. 43-50
Author(s):  
D. V. Kassina ◽  
I. A. Vasilenko ◽  
A. S. Gur’ev ◽  
A. Yu. Volkov ◽  
V. B. Metelin

Rationale: An important element of antiviral defense in the pathophysiology of COVID-19 is the innate cell immunity including polymorphonuclear neutrophils prone to netotic transformation. Neutrophils can be not only a marker of acute infection, but, being a source of neutrophil extracellular traps (NET), can play a key role in the development of thrombotic complications leading to acute respiratory insufficiency in COVID-19.Aim: To determine the diagnostic and prognostic value of NET levels in patients with COVID-19.Materials and methods: We monitored NET levels in peripheral blood of 34 patients with COVID-19 (mean age, 67 ± 15.8 years), admitted to MONIKI hospital. The control group consisted of 54 healthy volunteers (mean age, 52 ± 11.5 years). Whole blood samples of 2 pL each were used for the preparation of monolayer smears (Giemsa stain) and calculation of at least 200 cell structures including native intact and transformed neutrophils (MECOS-C2 microscope, Medical computer systems).Results: Patients with COVID-19 had higher NET levels, compared to those in healthy controls: 14.5% (2.9-28.6%) vs. 5.0% (1.8-11.9%, p < 0.0001). The patients who were on non-invasive respiratory support (23.5%) had a NET level of 12% (8.122.3%), whereas those on invasive mechanical ventilation (17.6%) had a 1.5-fold higher NET level of 17.9% (12.3-28.2%) (p < 0.05). In the patients who died (11.8% of the cases), the NET level amounted to 19% (16.5-26%, p < 0.05). Monitoring of blood NET levels was performed in 9 patients from the day of admittance to the day of their transfer to the intensive care unit / discharge / death. It was shown that a decrease of NET levels mirrors an improvement of the patient's clinical condition and efficacy of his/hers treatment. On the opposite, an increase of NET levels can indicate a deterioration and risk of unfavorable course.Conclusion: We have identified some pathophysiological mechanisms in COVID-19, related to the neutrophil compartment. Patients with coronavirus infection are characterized by high NET levels which is at least 3-fold higher than that in healthy volunteers. This indicates an abnormality in immune host defense and development of an inadequate inflammatory response. An increase of NET in whole blood smears of more than 16% can be a criterion of an unfavorable prognosis of the disease course and the risk of death.

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Axel Rosell ◽  
Katherina Aguilera ◽  
Yohei Hisada ◽  
Clare Schmedes ◽  
Nigel Mackman ◽  
...  

AbstractPredicting survival accurately in patients with advanced cancer is important in guiding interventions and planning future care. Objective tools are therefore needed. Blood biomarkers are appealing due to their rapid measurement and objective nature. Thrombosis is a common complication in cancer. Recent data indicate that tumor-induced neutrophil extracellular traps (NETs) are pro-thrombotic. We therefore performed a comprehensive investigation of circulating markers of neutrophil activation, NET formation, coagulation and fibrinolysis in 106 patients with terminal cancer. We found that neutrophil activation and NET markers were prognostic in terminal cancer patients. Interestingly, markers of coagulation and fibrinolysis did not have a prognostic value in this patient group, and there were weak or no correlations between these markers and markers of neutrophil activation and NETs. This suggest that NETs are linked to a poor prognosis through pathways independent of coagulation. Additional studies are needed to determine the utility of circulating neutrophil activation and NET markers, alone or in concert with established clinical parameters, as objective and reliable prognostic tools in advanced cancer.


2020 ◽  
Vol 2020 ◽  
pp. 1-5
Author(s):  
Vilen Molotov-Luchanskiy ◽  
Altynbek Nukhuly ◽  
Larissa Muravlyova ◽  
Ryszhan Bakirova ◽  
Aruna Kossybayeva ◽  
...  

Background and Objectives. Community-acquired pneumonia (CAP) has a high mortality rate among adult patients throughout the world. The highest mortality is registered in the older age group with a steady increase in the number of cases of morbidity among persons of working age. Neutrophils are one of the most urgent areas of research, since their condition largely determines the development and outcome of acute pneumonia. We study the indices of oxidative stress and oxidized-modified proteins of neutrophils in CAP patients, depending on the degree of severity, and also compare the detection frequency of neutrophil extracellular traps in the progression of pneumonia. Materials and Methods. 51 patients with CAP were divided into 2 groups depending on the severity of the pathological process. The first group (I) consisted of 32 patients with moderate severity of pneumonia. The second group (II) consisted of 19 patients with severe pneumonia. The third group (III), the comparison group, consisted of 14 CAP patients with chronic obstructive pulmonary disease (COPD). The control group consisted of 19 volunteers. Results. Statistically significant increase in the level of carbonyl derivatives (CD) in patients of all study groups relative to the control group was revealed. In the group of patients with moderate severity and severe pneumonia, also in CAP patients with COPD, the level of CD exceeded the control group. There was no statistically significant difference in the level of advanced oxidation protein products (AOPP) and myeloperoxidase (MPO) in blood neutrophils between the studied groups. Conclusion. Results indicate an oxidative imbalance in neutrophils and contribute to the worsening of the course of the disease.


Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 1345-1345 ◽  
Author(s):  
Tobias Fuchs ◽  
Alexander Brill ◽  
Daniel Dürschmied ◽  
Daphne Schatzberg ◽  
John H. Hartwig ◽  
...  

Abstract Abstract 1345 Introduction Thrombus stability is provided by very large polymers adhering to platelets and anchoring the thrombus to the vessel wall. The best described polymers are fibrin and von Willebrand Factor (VWF). Activated neutrophils and other leukocytes can form an extracellular fibrous network which is composed of DNA, histones, and granular proteins. These neutrophil extracellular traps (NETs) are present in various inflammatory diseases. In deep vein thrombosis (DVT) inflammation closely cooperates with thrombosis. Here we examine whether NETs provide a new means to support the adhesion and recruitment of platelets and whether NETs are present in DVT. Methods and Results: To study the interaction of platelets with NETs, we isolated human neutrophils, induced NET formation and perfused over the NETs human platelets in plasma or whole blood anticoagulated with the thrombin inhibitor PPACK. Microscopic analysis revealed that under flow platelets adhere avidly to NETs. Perfusion of whole blood at physiological shear resulted in formation of thrombi on NETs in a time dependent manner. Addition of DNase1 degraded NETs and removed all platelets and thrombi demonstrating their adhesion to NETs. Thrombus formation on NETs was absent if blood was supplemented with EDTA indicating the requirement for divalent cations. Perfusion of NETs with heparinized blood dismantled NETs and prevented thrombus formation. Incubation of NETs with heparin alone released histones from NETs, indicating that heparin destroys the chromatin backbone of NETs. Furthermore, immunocytochemistry revealed that NETs were able to bind platelet adhesion molecules VWF and fibronectin from human plasma. Immunohistochemical analysis of a baboon deep vein thrombus showed abundant extracellular chromatin which co-localized with fibronectin and VWF. Conclusions: We show that extracellular traps are able to promote thrombosis in vitro and are abundant in vivo in DVT. We propose that extracellular chromatin provides a new type of scaffold that promotes platelet adhesion, activation, and aggregation and may be important for thrombus initiation or stability. Disclosures No relevant conflicts of interest to declare.


2019 ◽  
Vol 40 (1) ◽  
pp. 4-11
Author(s):  
A. S. Nikonenko ◽  
O. O. Tanska

Purpose of the study. Study ST2 diagnostic marker in the development and severity of heart failure, evaluation of transplant status and the risk of developing a rejection crisis, as well as the risk of death in patients with cardiovascular disease.Material and methods. There were 41 patients under observation. The cases were conventionally divided into two groups: the first group of patients with chronic heart failure (n = 28), and the control group who performed orthotopic transplantation of the heart (n = 13).Results and discussion. These results suggest that ST2 is a real marker of chronic heart failure or a good predictor of mortality in decompensated patients. Changes in ST2 levels in patients after orthotopic cardiac transplantation may be potentially useful in detecting acute cellular rejection, as well as in controlling rejection therapy. The article is devoted to the analysis of the prognostic role of the ST2 biomarker in the pre and post-transplantation period. ST2 is one of the most promising diagnostic markers for the development and severity of heart failure, as well as the risk of death in patients with cardiovascular disease. ST2 is expressed in cardiomyocytes in response to pathological processes and various mechanical damage in the heart, which allows to diagnose cardiovascular diseases even before clinical manifestations. It is likely that ST2 level measurement of heart transplantation may have a diagnostic and prognostic value when evaluating the graft state and the risk of developing rejection.Conclusions. ST2 is one of the most promising diagnostic markers of development and severity of heart failure, as well as the risk of death in patients with cardiovascular disease. ST2 is expressed in cardiomyocytes in response to pathological processes and various mechanical damage in the heart, which allows to diagnose cardiovascular diseases even before clinical manifestations. Measuring the level of ST2 for heart transplantation may have a diagnostic and prognostic value in evaluating the condition of the graft and the risk of developing rejection. Keywords:heart failure, ST2, heart transplantation, rejection crisis.


2017 ◽  
Vol 21 (2) ◽  
pp. 24-32 ◽  
Author(s):  
O. B. Kuzmin ◽  
V. V. Zhezha ◽  
V. V. Belaynin ◽  
N. V. Buchneva ◽  
L. N. Landar ◽  
...  

The review summarized data on the diagnostic and prognostic value of biomarkers of kidney injury NGAL (neutrophil gelatinaseassociated lipocalin), KIM-1 (kidney injury molecule-1) and L-FABP (liver type fatty acid-binding protein) in patients with CKD. The most studied of these is NGAL, increase of its level in urine reflects the severity of CKD. Elevated levels of urinary NGAL evaluated also as a prognostic criterion which allows identifying patients with high risk of unfavorable course of disease. Elevated levels of urinary KIM-1 inpatients with CHF can detect individuals with tubulointerstitial kidney injury, having an adverse prognostic value, and to assess their risk of death or rehospitalization about CHF. Data obtained in large populations of patients with diabetes type 1 and 2 with CKD show that high levels of urinary L-FABP is associated with an increased risk of diabetic nephropathy progression. High levels of this biomarker in urine of patients with diabetes type 2 and stage1-2 CKD is also unfavorable prognostic marker of increased risk of coronary heart disease and other cardiovascular complications. In general, diagnostic and prognostic value of urine KIM-1 and L-FABP in CKD patients with varying severity poorly understood and needs further clinical studies. 


2020 ◽  
Vol 10 (2) ◽  
pp. 204589401989977 ◽  
Author(s):  
Lili Wang ◽  
Xiaoling Chen ◽  
Ke Wan ◽  
Chao Gong ◽  
Weihao Li ◽  
...  

The right ventricle experiences dynamic changes under pressure overload in pulmonary artery hypertension. This study aimed to evaluate the diagnostic and prognostic value of right ventricular eccentricity index (RVEI) in pulmonary artery hypertension. A total of 100 pulmonary artery hypertension patients (mean age, 36.85 (SD, 13.60) years; males, 30.0%) confirmed by right heart catheterization and 147 healthy volunteers (mean age 45.58 (SD, 17.58) years; males, 42.50%) were enrolled in this prospective study. All participants underwent cardiac magnetic resonance imaging (MRI) examination, and balanced steady-state free precession (bSSFP) cine sequences were acquired. RVEI was measured on short-axis cine images at the mid-ventricular level of the right ventricle in end systole. The study found that RVEI was significantly lower in pulmonary artery hypertension patients than in healthy volunteers (1.84 (SD, 0.40) vs. 2.46 (SD, 0.40); p < 0.001). In pulmonary artery hypertension patients, RVEI was correlated with log(NT-proBNP) (r = −0.388; p < 0.001), right ventricular end-diastolic volume index (r = −0.452; p < 0.001), right ventricular end-systolic volume index (r = −0.518; p < 0.001), and right ventricular ejection fraction (r = 0.552; p < 0.001). RVEI could discriminate pulmonary artery hypertension patients from healthy volunteers with 91.8% sensitivity and 68.0% specificity. Over median follow-up of 14.8 months (interquartile range: 6.7–26.9 months), RVEI was demonstrated to be an independent predictor for adverse outcome (HR = 0.076; 95% CI, 0.013-0.458; p = 0.005). In conclusion, MRI-derived RVEI appears to be a useful diagnostic and prognostic value in pulmonary artery hypertension, and it provides incremental value to risk stratification strategy.


Angiology ◽  
2021 ◽  
pp. 000331972110260
Author(s):  
Selim Görgün ◽  
Şener Cindoruk ◽  
Emre Özgen ◽  
Metin Yadigaroğlu ◽  
Mehmet Tevfik Demir ◽  
...  

We aimed to evaluate whether there was a relationship between endocan (human endothelial cell-specific molecule-1) levels and disease prognosis in patients who presented to the emergency department with coronavirus disease 2019 (COVID-19). A total of 60 patients with COVID-19 who were hospitalized from the emergency department to clinical wards and a control group consisting of healthy adult individuals (n = 28), were included in the study. The majority (93.3%) of the patients were discharged after recovery; 6.7% died. The median endocan value was 243.5 ng/mL in the patient group versus 201.5 ng/mL in the control group ( P = .002). The median endocan level was 240.5 ng/mL in those discharged with recovery and 558 ng/mL in those who died ( P = .001). There was no significant relationship in hospitalization duration, sex, tomography findings, and clinical outcomes. A 202 ng/mL serum endocan level had 86.7% sensitivity and 50% specificity for COVID-19. Serum endocan levels may be a useful biomarker both for the diagnosis of COVID-19 and to predict mortality.


2020 ◽  
Vol 26 ◽  
pp. 107602962097104
Author(s):  
Kun Zhou ◽  
Jun Zhang ◽  
Zun-Rong Zheng ◽  
Yu-Zhen Zhou ◽  
Xun Zhou ◽  
...  

Background: Venous thromboembolism (VTE) is an important complication in patients with malignant tumors. Its exact diagnosis and treatment are still lacking. We used a high-sensitive chemiluminescence method to detect thrombin–antithrombin III complex (TAT), plasmin-α2-plasmininhibitor complex (PIC), thrombomodulin (TM), and tissue plasminogen activator–inhibitor complex(t-PAIC) in combination with D-dimer and fibrin degradation product (FDP) to analyze their diagnostic and prognostic value in patients with malignant tumors. Methods: In total, 870 patients with confirmed malignant tumors were included, 82 of whom had diagnosed VTE; 200 healthy individuals were classified as the control group. The TAT, PIC, TM, and t-PAIC were detected using Sysmex HISCL5000 automated analyzers, whereas FDP and D-dimer were detected using Sysmex CS5100 coagulation analyzer. Receiver operating characteristic (ROC) curves were used to evaluate the diagnostic efficiency. Survival probabilities were determined using Kaplan–Meier analysis, and multivariate analyses were performed using a Cox regression model. Results: Compared with healthy controls, patients with malignant tumors showed significantly elevated TAT, PIC, TM, t-PAIC, D-dimer, and FDP. Similarly, compared with patients in the non-thrombosis group, those in the thrombosis group showed significantly elevated levels of the above mentioned markers. Logistic regression analysis showed that TAT, PIC, TM, t-PAIC, D-Dimer, and FDP were all associated with VTE. ROC analysis showed that “TAT+PIC+TM+t-PAIC+D-dimer+FDP”showed the highest sensitivity and specificity. Patients with elevated TAT, PIC, TM, and t-PAIC had a significantly shorter survival. Multivariate Cox survival analysis showed that TM and t-PAIC were significantly associated with poor prognosis. In addition, the incidence of VTE was significantly lower in patients with malignant tumors who were treated with low-molecular-weight heparin (LMWH), and their survival period was significantly longer than that of patients with malignant tumors who were not treated with LMWH. Conclusion: TAT, PIC, TM, and t-PAIC combined with D-dimer and FDP were better than the application of a single marker in the diagnosis of VTE in patients with malignant tumors. TAT and PIC can be used as sensitive markers in the diagnosis of VTE but not as prognostic markers. TM and t-PAIC might be independent prognostic indicators in patients with malignant tumors, regardless of the state of thrombus.


2020 ◽  
Vol 2020 ◽  
pp. 1-8
Author(s):  
Beata Smok ◽  
Krzysztof Domagalski ◽  
Małgorzata Pawłowska

Purpose. The aim of this study was to evaluate the diagnostic and prognostic value of IL-6 and sTREM-1 in the course of SIRS and sepsis in children with reference to routinely used CRP and PCT. Methods. A prospective study included 180 patients at the ages from 2 months to 18 years hospitalized due to fever from November 2015 to January 2017. Forty-nine children without fever hospitalized due to noninfectious causes formed the control group. IL-6 and sTREM-1 serum concentrations were assessed with the enzyme-linked immunosorbent assay method. Results. The mean serum concentrations of all the analyzed biomarkers were statistically significantly higher in the study group compared to the control group. Mean IL-6, sTREM-1, and PCT serum concentrations were statistically significantly higher in the group of patients with SIRS/sepsis compared to the group of feverish patients without diagnosed SIRS (N-SIRS). Based on the ROC curve analysis, it was shown that of all the biomarkers tested, only two—IL-6 and procalcitonin—had potential usefulness in the diagnosis of SIRS/sepsis in children with fever. Conclusion. Elevated levels of IL-6 and PCT are important risk factors for the development of SIRS/sepsis in children with fever. It seems that elevated IL-6 baseline serum level may predict a more severe course of febrile illness in children, because based on the ROC curve analysis, it was found that IL-6 is a statistically significant prognostic marker of prolonged fever≥3 days and prolonged hospitalization>10 days. The assessment of the usefulness of sTREM-1 in the diagnosis of SIRS/sepsis in feverish children requires further research.


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