Histone H3 Cleavage in Severe COVID-19 ICU Patients

Area of Science:

• Immunology and Infectious Diseases
• Critical Care Medicine
• Molecular Biology

Background:

• Severe COVID-19 is linked to neutrophil extracellular trap (NET) formation, releasing cytotoxic extracellular histones.
• Extracellular histones are implicated in the pathogenesis of acute inflammatory conditions.
• Understanding histone presence and modification in COVID-19 is crucial for developing targeted therapies.

Purpose of the Study:

• To investigate the presence and evolution of extracellular histone H3 and related molecules in critically ill COVID-19 patients.
• To correlate histone levels and modifications with clinical outcomes and disease severity.

Main Methods:

• Plasma samples from 117 COVID-19 ICU patients were analyzed for extracellular histone H3, MPO, and DNA-MPO complexes.
• Levels were compared between ICU admission and later time points (4+ days).
• Histone proteolysis and associations with clinical events were assessed.

Main Results:

• Significantly increased levels of histone H3, MPO, and DNA-MPO complex were observed in COVID-19 patients upon ICU admission.
• Elevated marker levels persisted in a subset of patients throughout their ICU stay.
• Histone H3 presence correlated with thromboembolic events, secondary infections, and severe clinical manifestations including acute kidney injury.

Conclusions:

• Extracellular histones are key biomarkers and potential drivers of severe COVID-19 pathology.
• Data support therapeutic strategies targeting NET formation and histone neutralization.
• Non-cleaved histone H3 is associated with critical illness severity and organ dysfunction.