Covid-19: Possible Role of Neutrophil Extracellular Traps
试验速览
- 阶段
- 不适用
- 入组人数
- 100
- 试验地点
- 1
- 主要终点
- NETOSIS AND MORTALITY
研究概览
简要总结
The process by which neutrophils expel DNA together with various proteins to the outside, forming a network structure called Neutrophil Extracellular Traps (NETs) constitutes a particular cell death that involves the destruction of the nuclear membrane before the plasmatic one. This process is called NETosis and differs from other known forms of cell death, such as necrosis and apoptosis.
This process, however, if exaggerated, brings local or systemic damage. Viruses are known for their ability to evade the body's immune response. Only recently has it been seen that they can act as triggers for NETosis process.
In fact, many viruses can stimulate neutrophils to produce NETs. Virus-induced NETs can begin to circulate in an uncontrolled manner, leading to an extreme systemic response of the body with the production of immunocomplexes, cytokines, Interferon I etc.
To date, there are no data in the literature on the role of NETs in Covid-19 infection, a viral infection that leads to highly lethal interstitial pneumonia and for which there is currently no vaccine or specific therapy.
Advanced forms of Covid-19 are often characterized by hyperinflammation ("cytokine storm") with the development of an ARDS-like condition. Furthermore, reports of micro and macro thrombotic phenomena such as microangiopathy, pulmonary embolism (which has led to a careful evaluation procedure for antithrombotic prophylaxis and/or coagulation in Covid-19 patients) are increasingly frequent.
The primary objective of the study is to understand if NETs can be implicated in the response to Covid-19 and by which mechanisms. Concrete therapeutic proposals could derive from the knowledge and enhancement of this form of innate immunity.
To do this, it will be necessary to evaluate the activity of NETosis in Covid-19 patients and evaluate whether the clinical course of the disease (worsening vs healing) determines the degree of NETosis activity. Therefore, the association between mortality from Covid-19/survival and NETs activity will be studied.
Secondary objectives concern the possibility of studying the associations among NETosis markers and blood inflammation markers and among NETosis markers and the onset of peripheral or deep vein thrombosis.
Finally, the possibility that the plasma deriving from Covid-19 patients could trigger the NETosis process in vitro will be evaluated.
详细描述
The process by which neutrophils expel DNA together with various proteins to the outside, forming a network structure called Neutrophil Extracellular Traps (NETs) constitutes a particular cell death that involves the destruction of the nuclear membrane before the plasmatic one. This process is called NETosis and differs from other known forms of cell death, such as necrosis and apoptosis.
Neutrophil death by NETs ejection (NETosis) was first described in 2004 by Brinkman.
NETs,as indicated by the word itself, represent a sort of network composed of DNA fibers, histones and proteins derived from the neutrophil granules, whose main function is to trap pathogens (mainly bacteria and fungi).This process is related to the innate immunity.
However, this process, if activated in an exaggerated way, implies itself local or systemic damage.
The DNA expelled during this process is a double stranded DNA, a dsDNA subtype. The dsDNA, which represents a fraction of the DNA available in the circulation (cell free DNA - cfDNA), originates from various processes of cell death, and is therefore correlated with the degree of tissue damage. It is present only in small quantities in healthy subjects.
研究设计
- 研究类型
- Observational
- 观察模型
- Case Control
- 时间视角
- Prospective
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- 未提供
排除标准
- •age <18 years;
- •pregnancy;
- •known autoimmune diseases.
- •For the control group:
- •positivity to Covid-19 swabs and / or the presence of IgM and IgG antibodies (sierological picture known from the samples taken by the Health surveillance System of the hospital).
结局指标
主要结局
NETOSIS AND MORTALITY
时间窗: 1 year
correlation among plasma levels of NETosis markers and Covid-19 mortality
NETOSIS AND DCOVID-19 SEVERITY
时间窗: 1 year
correlation among plasma levels of NETosis markers and disease severity (that is duration of hospitalization in days and any need for passage to intensive care with non-invasive ventilation or intubation);
次要结局
- NETOSIS AND INFLAMMATION(1 year)
- NETOSIS AND VENOUS THROMBOSIS(1 year)
研究者
Chiara Mozzini
Principal Investigator
Azienda Ospedaliera Universitaria Integrata Verona