TY - JOUR
AU - Shaw, Rebecca J
AU - Abrams, Simon
AU - Austin, James
AU - Taylor, Joseph M
AU - Lane, Steven
AU - Dutt, Tina
AU - Downey, Colin
AU - Du, Min
AU - Turtle, Lance C.W.
AU - Baillie, J. Kenneth
AU - Openshaw, Peter J.M.
AU - Wang, Guozheng
AU - Semple, Malcolm G.
AU - Toh, Cheng-Hock
PY - 2021
DA - April
TI - Circulating histones play a central role in COVID-19-associated coagulopathy and mortality
JO - Haematologica
DO - https://doi.org/10.3324/haematol.2021.278492
AB - 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.
PB - Ferrata Storti Foundation
UR - https://www.research.ed.ac.uk/portal/en/publications/circulating-histones-play-a-central-role-in-covid19associated-coagulopathy-and-mortality(17afa2fe-bf12-4b47-b9a7-ac36b173ae4b).html
KW - Coronavirus (COVID-19)
ER