Background: Early therapeutic anticoagulation may decrease thrombotic and non-thrombotic complications in infection with SARS-CoV-2 (COVID-19), improving outcomes. Accurately targeting only high risk patients would improve safety of this approach; blood-based biomarkers to accurately risk-stratify would be of value. Dysregulated neutrophil extracellular traps (NETs) drive pulmonary inflammation, thrombosis and mortality and may therefore represent a useful biomarker. NETs determined via free DNA quantification are elevated in severe COVID-19 and correlate with outcome, but the technical requirements of these tests preclude their clinical use.  

Aims: We assessed the potential of a clinically-applicable immunoassay for the quantification of cell free H3.1-nucleosome as a NETs biomarker and predictor of thrombosis and mortality.

Methods: Plasma samples on admission, day 3, 7 and 10 were evaluated from 20 patients with severe COVID-19 requiring organ support (severe cohort) and compared with 28 samples from COVID-19 patients requiring hospitalization, but not organ support (non-severe cohort). Circulating H3.1-nucleosomes were measured using Nu.Q™ H3.1-nucleosome ELISA (Belgian Volition SRL, Isnes, Belgium) as per manufacturer’s instruction.

Results: Panel 1a: Illustrates H3.1-nucleosome levels (ng/ml) in non-severe versus severe COVID-19 patients and the group median. Panel 1b: Charts the median and range of values for H3.1-nucleosome levels (ng/ml) over the first 10 days of ITU admission in severe patients who survived versus those who died upto 28 days.
Patient demographics: Severe cohort: Age (median/range)= 63(43-84). Gender distribution: F=5, M=15. Non-severe cohort: Age= 51.5(28-80). F=11, M=17. H3.1 nucleosome levels were significantly elevated in the severe versus non-severe cohort (figure 1a). H3.1 nucleosome levels could not be used to predict thrombotic outcome, but there was an association with 28 day mortality, with significantly higher admission values recorded in ITU patients who died (Mann-whitney P=0.014, n=6) and comparatively higher H3.1-nucleosome values maintained during day 1-7 of ITU admission (figure1b).

Conclusions: The immunoassay NETs biomarker replicated findings of free DNA quantification studies; NETs correlate with disease severity. Although of no value in predicting thrombosis in this study, there is an indication that elevated values predict poor outcomes in patient admitted to ITU and may be of value in risk stratifying to treatments such as therapeutic anticoagulation and tracking response to treatment.

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ISTH Congress Abstracts - https://abstracts.isth.org/abstract/circulating-nucleosome-immunoassay-evaluating-a-clinically-applicable-test-to-risk-stratify-covid-19-and-target-anticoagulation/