@article{Shaw_R-2021_26893,
title = {Circulating histones play a central role in COVID-19-associated coagulopathy and mortality},
author = {Shaw, R. and Abrams, S. and Austin, J. and Taylor, J. and Lane, S. and Dutt, T. and Downey, C. and Du, M. and Turtle, L. and Baillie, J. and Openshaw, P. and Wang, G. and Semple, M. and Toh, C.},
month = {apr},
year = {2021},
abstract = {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&lt;.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.},
journal = {Haematologica},
publisher = {Ferrata Storti Foundation},
url = {https://doi.org/10.3324/haematol.2021.278492},
}
