PB0097 - Intracellular nuclear proteins histone H3 and HMGB1 are predictive markers of disease severity and prognosis of COVID-19 patients

Background: COVID-19 still has an overwhelming influence not only on human health but also on economics worldwide in 2023. COVID-19 is complicated by coagulopathy and has poor prognosis; however, the etiology of COVID-19-associated coagulopathy remains to be fully elucidated. The intracellular nuclear proteins histone H3 (H3) and HMGB1 play a role in the development of DIC by activating the coagulation systems and platelets in patients with sepsis and acute leukemia and were associated with poor prognosis of DIC patients.

Aims: The present study explores whether intracellular nuclear proteins would be associated with the coagulopathy, disease severity and prognosis of COVID-19 patients.

Methods: The serum levels of H3 and HMGB1 and plasma levels of d-dimer were measured in the consecutive COVID-19 patients (n=379) admitted to our hospital and one affiliated hospital from Feb 2020 to Aug 2021. The association between these values and the disease severity and prognosis was evaluated by either Kruskal-Wallis and Mann-Whitney U test, respectively.

Results: The patients were categorized into four groups according to the disease severity (mild, no respiratory symptom; moderate 1, having respiratory symptom; moderate 2, requires oxygen inhalation; severe, admitted to the intensive care unit). The serum levels of both H3 and HMGB1 increased with increasing disease severity. Twenty patients died by day 60 after admission in whom intracellular nuclear protein levels were higher than those who survived beyond day 60. Similarly, plasma levels of d-dimer increased with increasing disease severity and were significantly higher in non-survivors than survivors. However, no correlation between levels of intracellular nuclear proteins and d-dimer was noted as assessed by Pearson correlation analysis in this study cohort.

Conclusion(s): Multiple-factors including intracellular nuclear proteins may play a role in the development of COVID-19-associated coagulopathy. Measurement of circulating H3 and HMGB1 is useful to predict the disease severity and prognosis of COVID-19 patients.