Functional proteomic profiling links deficient DNA clearance with increased mortality in individuals with severe COVID-19 pneumonia 

A new publication suggests that deficient DNA clearance is linked to increased mortality in individuals with severe COVID-19 pneumonia. The publication was accepted on Nov. 15 and will soon appear in Immunity. It is co-authored by Prof Sascha David, Dr Klaus Stahl and Dr Christian Bode, who will take part in the future of Santersus as Principle Investigators (PIs) of our upcoming clinical trial of NucleoCapture in critically unwell patients with sepsis in the ICU.

The authors used murine sepsis models to demonstrate that splenocyte death interfered with chromatin clearance through the release of the DNase I inhibitor actin. Actin inhibition was compensated by upregulation of DNase I or the actin cavenger gelsolin. Splenocyte death and neutrophil extracellular trap (NET) clearance deficiencies were prevalent in individuals with severe COVID-19 pneumonia or microbial sepsis. Activity tracing by plasma proteomic profiling uncovered an association between low NET clearance and increased COVID-19 pathology and mortality. Low NET clearance activity with comparable proteome associations was prevalent in healthy donors with low-grade inflammation, implicating defective chromatin clearance in the development of cardiovascular disease and linking COVID-19 susceptibility to pre-existing conditions. Hence, the combination of aberrant chromatin release with defects in protective clearance mechanisms lead to poor survival outcomes.

Hence, this important publication reveals the profound impact of cell-free DNA clearance and its involvement in the survival of patients who suffer from severe SARS-CoV-2 infection. This obviously presents a novel therapeutic opportunity for our technology, NucleoCapture, which allows for selective removal of NETs from blood without compromising the defensive function of neutrophils.

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