COVID-19 has highlighted the lethal consequences of immunothrombosis; i.e. the cross-talk between coagulation, inflammation and the innate immune system.  These patients have significant immune cell death, which can release pro-coagulant and cytotoxic histones. Histones are small positively charged proteins, typically found within the cell nucleus, which bind to negatively charged DNA. We hypothesize that circulating histones play a central role in critically ill COVID-19 patients. This translational study demonstrates that admission histone levels were significantly elevated with increasing severity of COVID-19 infection (Mild, median=2.6µg/ml [IQR=0.7-7.6], Moderate, 10.5µg/ml [3.5-27.2], Critical, 20.0µg/ml [6.2-33.0], Non-survivors, 29.6µg/ml [11.2-60.0]; P<.001). Circulating histones associated with severe coagulopathy, inflammation and organ injury markers, including cardiac troponin. Extracellular histone levels on admission are associated with poor outcomes and independently predict 28-day mortality of hospitalised COVID-19 patients. This is the first report to indicate that circulating histones, released following immune cell death, may play a central pathological role in severe SARS-CoV-2 infection.


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Cite as

Shaw, R., Abrams, S., Austin, J., Taylor, J., Lane, S., Dutt, T., Downey, C., Du, M., Turtle, L., Baillie, J., Openshaw, P., Wang, G., Semple, M. & Toh, C. 2021, 'Circulating histones play a central role in COVID-19-associated coagulopathy and mortality', Haematologica. https://doi.org/10.3324/haematol.2021.278492

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Last updated: 16 June 2022
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