HMGB1 correlates with severity and death of COVID-19 patients

Abstract

SARS-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, PGE<2, 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.

Dual effects of supplemental oxygen on pulmonary infection, inflammatory lung injury, and neuromodulation in aging and COVID-19

“…Interestingly, HMGB1 can increase the expression of ACE2 (a protein involved in the cellular entry of SARS-CoV-2 in host cells) in cultured human lung epithelial cells, liver cells, intestine cells, and urinary bladder cells (R [ 176 ]. Furthermore, patients with severe COVID-19 have significantly higher serum levels of HMGB1, compared to patients diagnosed with mild cases (L. [ 177 ]; R [ 17 , 33 , 178 , 179 ]. Importantly, increased serum levels of HMGB1 are positively correlated with COVID-GRAM risk scores in hospitalized patients (L. [ 48 ], and with the levels of cys-leukotrienes, D-dimer, AST and ALT [ 179 ].…”

“…Furthermore, patients with severe COVID-19 have significantly higher serum levels of HMGB1, compared to patients diagnosed with mild cases (L. [ 177 ]; R [ 17 , 33 , 178 , 179 ]. Importantly, increased serum levels of HMGB1 are positively correlated with COVID-GRAM risk scores in hospitalized patients (L. [ 48 ], and with the levels of cys-leukotrienes, D-dimer, AST and ALT [ 179 ]. HMGB1 levels greater than 125.4 ng/mL have been reported to be the cut off level that distinguishes patients that are at a high risk of death [ 179 ].…”

“…Importantly, increased serum levels of HMGB1 are positively correlated with COVID-GRAM risk scores in hospitalized patients (L. [ 48 ], and with the levels of cys-leukotrienes, D-dimer, AST and ALT [ 179 ]. HMGB1 levels greater than 125.4 ng/mL have been reported to be the cut off level that distinguishes patients that are at a high risk of death [ 179 ]. The serum levels of HMGB1 at the early inflammatory phase of the disease can have a predictive value for the pathogenic outcome, including the occurrence of the increased levels of cytokines and chemokines and the increased probability of death in these patients [ 179 ].…”

“…HMGB1 levels greater than 125.4 ng/mL have been reported to be the cut off level that distinguishes patients that are at a high risk of death [ 179 ]. The serum levels of HMGB1 at the early inflammatory phase of the disease can have a predictive value for the pathogenic outcome, including the occurrence of the increased levels of cytokines and chemokines and the increased probability of death in these patients [ 179 ]. Notably, all patients in this study received some form of supplemental oxygen [ 179 ].…”

“…The serum levels of HMGB1 at the early inflammatory phase of the disease can have a predictive value for the pathogenic outcome, including the occurrence of the increased levels of cytokines and chemokines and the increased probability of death in these patients [ 179 ]. Notably, all patients in this study received some form of supplemental oxygen [ 179 ]. Thus, the serum level of HMGB1 may represent a prognostic biomarker for the risk of death in severe COVID-19, and a novel target for the treatment of patients diagnosed with severe COVID-19.…”