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Authors: Yu Zuo el Al Link to paper:

Pre-Print: medrxiv

Key Words: neutrophils, NETs, MPO-DNA , Cit-H3 and COVID19

Research Highlights 

· First report on potential neutrophil functions involved in severe cases of Covid-19.

· Various markers of NETosis in serum corelate with the illness severity.

· Ventilation might cause more cellular and tissue damage as evidenced by elevated free serum DNA.


Elevated levels of blood neutrophils are reported to predict worse outcomes in COVID-19. In this study Yu Zuo et al measure neutrophil NETosis in COVID-19 patients. Authors use three markers to detect NET remnants in blood. These markers are cell-free DNA, Cit-H3, and MPO-DNA in patients with COVID 19 compared to healthy patients. They report elevated levels of cell-free DNA, (MPO)-DNA, and (Cit-H3) in COVID19 patients. Cell-free DNA was closely associated with inflammatory markers used to track COVID-19 including C-reactive protein, D-dimer, and lactate dehydrogenase. It was strongly correlated with absolute neutrophil count. Cell-free DNA and MPO-DNA were also higher in hospitalized patients receiving mechanical ventilation as compared with hospitalized patients breathing room air. NETs have potential to propagate inflammation and microvascular thrombosis including in the lungs of patients with acute respiratory distress syndrome.

Impact for SARS-CoV2/COVID19 research efforts

· Potential clinical diagnosis marker of cell free DNA in Covid-19

· Open up opportunities to develop therapeutic intervention targeting NET formation in neutrophils in Covid-19

Study Type

· Ex vivo study: analysis of serum from COVID-19 patients

Strengths and limitations of the paper


• Ease of application of serum cell free DNA measurement in clinical settings

• Set up foundation for further mechanistic investigation on neutrophil NET release which will shed light on potential pathogenesis roles of neutrophils in response to or in driving the cytokine storm

Standing in the field: yes

Appropriate statistics: yes

Viral model used: No virus used, but serum samples are from Covid-19 patients

Main limitations:

• Sources of cell-free DNA in the circulation can be from necrosis of neutrophils or other immune cells. Therefore, increased serum DNA level observed in patients under ventilation can be from mechanical damage.

· The use of serum (plasma is typically preferred for measurements of NETs)