Neutrophil extracellular traps (NETs) as markers of disease severity in COVID-19
cell biology diagnostics immunology/immunity therapeutics
Authors: Yu Zuo el Al Link to paper: https://www.medrxiv.org/content/10.1101/2020.04.09.20059626v1
Key Words: neutrophils, NETs, MPO-DNA , Cit-H3 and COVID19
· 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
· 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
• 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)