ABSTRACT
Background: Histones (i.e., positively charged nuclear proteins) are key components in chromatin functions that under physiological conditions contribute to DNA packaging and regulate gene expression, but they are significantly mobilized in blood and body fluids during cell and tissue injuries in several pathological processes. Histones mediate both inflammatory pathways and coagulative cascade, crucially linked to the severity and mortality of many human pathologies (e.g., thrombosis, sepsis, COVID-19). SARS-CoV-2 and sepsis infections share common laboratory biomarkers, such as Monocyte Distribution Width (MDW), that is mainly linked to the heterogeneity of monocyte volume;these modifications, upon massive inflammatory activation, predict multiorgan dysfunction and increased mortality rate in several pathological conditions. No data are available on the roles of histones as MDW modifiers. Method(s): Comparison of MDW index was undertaken by hematology analyzer UniCell DxH900 Hematology Analyzer (Beckman Coulter) on whole blood samples from patients with COVID-19 and Sepsis. The impact of histones on the MDW characteristics was assessed by the in vitro time-dependent treatment of healthy control whole blood with histones and histones+lipopolysaccharide. Result(s): We demonstrated the breadth of early, persistent, and significant increase of MDW index in whole blood from healthy subject treated in vitro with histones, highlighting changes similar to those found in vivo in classic and viral sepsis patients. The findings of MDW changes are confirmed by digital microscopy of blood smears, highlighting the histone-induced modifications of cell volume, cytoplasmic vacuolization, and nuclear structure alterations of the circulating monocytes. Conclusion(s): Histones contribute to the pronounced and persistent monocyte alterations observed in classical and viral sepsis. Assessment of the biological impact of circulating histone released during COVID-19 and sepsis on monocytes should be considered as key factor modulating both thrombosis and inflammatory processes, as well as the importance of neutralization of their cytotoxic and procoagulant activities by several commercially available drugs (e.g., heparins and heparinoids).