HMGB1 correlates with severity and death of COVID-19 patients

Abstract

ABSTRACTSARS-CoV-2, the causative agent of the ongoing COVID-19, has spread worldwide since it was first identified in November 2019 in Wuhan. Since then, it was already demonstrated an exuberant inflammation, cytokine storm, endothelium dysfunction, platelets hyperactivation and aggregation, following T cell exhaustion leading to severe multi-organ damage and death of COVID-19 patients. Here, we sought to identify molecular biomarkers of disease severity in a Brazilian cohort of COVID-19 patients by measuring the serum levels of endogenous danger signals. Our data revealed that ICU patients that are critically ill, at the early hyperinflammatory phase of COVID-19 (around 12-25 days after hospital admission) display higher serum levels of the classical alarmin HMGB1. Serum levels of HMGB1 were positively correlated with cys-leukotrienes, D-dimer, AST, and ALT. Notably, we verified that HMGB1 levels above 125.4 ng/mL is the cut off that distinguishes the patients that are at higher risk of death. Serum levels of extracellular ATP, PGE2, LTB4, cys-LTs, and tissue factor were also elevated in the serum of ICU patients. In conclusion, we propose that serum levels of HMGB1 serve as prognostic biomarker of risk of death in patients suffering from severe COVID-19.