Correction to: Circulating Markers of Neutrophil Extracellular Traps Are of Prognostic Value in Patients With COVID-19

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.

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Diagnostic, Therapeutic Predictive, and Prognostic Value of Neutrophil Extracellular Traps in Patients With Gastric Adenocarcinoma

Frontiers in Oncology ◽

10.3389/fonc.2020.01036 ◽

2020 ◽

Vol 10 ◽

Author(s):

Yiyin Zhang ◽

Yangyang Hu ◽

Cui Ma ◽

Hua Sun ◽

Xiaoli Wei ◽

...

Keyword(s):

Gastric Adenocarcinoma ◽

Prognostic Value ◽

Neutrophil Extracellular Traps ◽

Extracellular Traps ◽

Predictive And Prognostic Value

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Autoantibodies stabilize neutrophil extracellular traps in COVID-19

10.1101/2021.03.31.21254692 ◽

2021 ◽

Author(s):

Yu Zuo ◽

Srilakshmi Yalavarthi ◽

Sherwin Navaz ◽

Claire Hoy ◽

Hui Shi ◽

...

Keyword(s):

Mechanical Ventilation ◽

Neutrophil Extracellular Traps ◽

Healthy Controls ◽

Oxygen Supplementation ◽

Dna Complexes ◽

Extracellular Traps ◽

Circulating Markers ◽

Clinical Associations ◽

Antibody Levels ◽

D Dimer

The release of neutrophil extracellular traps (NETs) by hyperactive neutrophils is recognized to play an important role in the thromboinflammatory milieu inherent to severe presentations of COVID-19. At the same time, a variety of functional autoantibodies have been observed in individuals with severe COVID-19 where they likely contribute to immunopathology. Here, we aimed to determine the extent to which autoantibodies might target NETs in COVID-19 and, if detected, to elucidate their potential functions and clinical associations. We measured global anti-NET activity in 171 individuals hospitalized with COVID-19 alongside 48 healthy controls. We found high anti-NET activity in the IgG and IgM fractions of approximately 40% and 50% of patients, respectively. There was a strong correlation between anti-NET IgG and anti-NET IgM, with high anti-NET antibody levels in general associating with circulating markers of NETs such as myeloperoxidase-DNA complexes and calprotectin. Clinically, anti-NET antibodies tracked with impaired oxygenation efficiency and elevated levels of circulating D-dimer. Furthermore, patients who required mechanical ventilation had higher levels of anti-NET antibodies than those who did not require oxygen supplementation. Mechanistically, anti-NET antibodies of the IgG isotype impaired the ability of DNases in healthy serum to degrade NETs. In summary, these data reveal high levels of anti-NET antibodies in individuals hospitalized with COVID-19, where they likely impair NET clearance and thereby potentiate SARS-CoV-2 mediated thromboinflammation.

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

Almanac of Clinical Medicine ◽

10.18786/2072-0505-2020-48-029 ◽

2020 ◽

Vol 48 ◽

pp. 43-50

Author(s):

D. V. Kassina ◽

I. A. Vasilenko ◽

A. S. Gur’ev ◽

A. Yu. Volkov ◽

V. B. Metelin

Keyword(s):

Healthy Volunteers ◽

Whole Blood ◽

Prognostic Value ◽

Acute Infection ◽

Invasive Mechanical Ventilation ◽

Neutrophil Extracellular Traps ◽

Control Group ◽

Risk Of Death ◽

Extracellular Traps ◽

Diagnostic And Prognostic Value

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.

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