Covid-19: Possible Role of Neutrophil Extracellular Traps
NETSINCOVID
1 other identifier
observational
100
1 country
1
Brief Summary
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.
Trial Health
Trial Health Score
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participants targeted
Target at P50-P75 for all trials
Started Jun 2020
1 active site
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Trial Relationships
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Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
May 26, 2020
CompletedStudy Start
First participant enrolled
June 1, 2020
CompletedFirst Posted
Study publicly available on registry
June 2, 2020
CompletedPrimary Completion
Last participant's last visit for primary outcome
December 31, 2020
CompletedStudy Completion
Last participant's last visit for all outcomes
December 31, 2021
CompletedJuly 8, 2020
July 1, 2020
7 months
May 26, 2020
July 7, 2020
Conditions
Keywords
Outcome Measures
Primary Outcomes (2)
NETOSIS AND MORTALITY
correlation among plasma levels of NETosis markers and Covid-19 mortality
1 year
NETOSIS AND DCOVID-19 SEVERITY
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);
1 year
Secondary Outcomes (2)
NETOSIS AND INFLAMMATION
1 year
NETOSIS AND VENOUS THROMBOSIS
1 year
Study Arms (2)
covid-19
Study population: Covid-19 patients aged ≥ 18 years admitted to the Covid sections of the Verona University Hospital. Based on the ongoing epidemic emergency and the lack of specific therapy, we believe that to date this should be the only INCLUSION CRITERION.
control
Control group: medical doctors and nurses working in the University Hospital of Verona without known autoimmune diseases nor cancer.
Interventions
NETosis markers (Cf-DNA. MPO-DNA, Cit-H3) and the cytokines IL-6 and IL-1β will be analyzed from the subjects' plasma. Spittle sample (or bronchoalveolar fluid if necessary for diagnostic-therapeutic purposes) will be collected and the detection of NETs at electron microscopy will be assessed.
Eligibility Criteria
Study population: Covid-19 patients aged ≥ 18 years admitted to the Covid sections of the Verona University Hospital. Control group: medical doctors and nurses worìking in the University Hospital of Verona.
You may not qualify if:
- 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).
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (1)
Univeristy of Verona
Verona, 37136, Italy
Related Publications (1)
Mozzini C, Girelli D. The role of Neutrophil Extracellular Traps in Covid-19: Only an hypothesis or a potential new field of research? Thromb Res. 2020 Jul;191:26-27. doi: 10.1016/j.thromres.2020.04.031. Epub 2020 Apr 27. No abstract available.
PMID: 32360977BACKGROUND
Biospecimen
serum
MeSH Terms
Conditions
Condition Hierarchy (Ancestors)
Study Officials
- STUDY CHAIR
DOMENICO GIRELLI, MD-PhD
Universita di Verona
Central Study Contacts
Study Design
- Study Type
- observational
- Observational Model
- CASE CONTROL
- Time Perspective
- PROSPECTIVE
- Target Duration
- 1 Year
- Sponsor Type
- OTHER
- Responsible Party
- PRINCIPAL INVESTIGATOR
- PI Title
- Principal Investigator
Study Record Dates
First Submitted
May 26, 2020
First Posted
June 2, 2020
Study Start
June 1, 2020
Primary Completion
December 31, 2020
Study Completion
December 31, 2021
Last Updated
July 8, 2020
Record last verified: 2020-07
Data Sharing
- IPD Sharing
- Will share
- Shared Documents
- STUDY PROTOCOL, SAP
- Time Frame
- end 2020
- Access Criteria
- mail contact
study protocol and results