High mobility group box 1, ATP, lipid mediators, and tissue factor are elevated in COVID-19 patients: HMGB1 as a biomarker of worst prognosis.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the agent of the ongoing COVID-19 pandemic, has spread worldwide since it was first identified in November 2019 in Wuhan. Since then, progress in pathogenesis linked severity of this systemic disease to the hyperactivation of network of cytokine-driven proinflammatory cascades. Here, we aimed to identify molecular biomarkers of disease severity by measuring the serum levels of inflammatory mediators in a Brazilian cohort of COVID-19 patients and healthy controls (HC). Critically ICU patients were defined as such by dependence on oxygen supplementation (93% intubated and 7% face mask), and CT profiles showing ground-glass opacity pneumonia associated to and high levels of D-dimer. Our panel of mediators included HMGB1, ATP, tissue factor (TF), PGE 2 , LTB 4 , and cys-LTs. Follow up studies showed increased serum levels of every inflammatory mediator in COVID-19 patients as compared to HC. Originally acting as a transcription factor, HMGB1 acquires proinflammatory functions following secretion by activated leukocytes or necrotic tissues. Serum levels of HMGB1 were positively correlated with cys-LTs, D-dimer, AST, and ALT. Notably, the levels of the classical alarmin HMGB1 were higher in deceased patients, allowing their discrimination from patients that had been discharged at the early pulmonary and hyperinflammatory phase of COVID-19. In particular, we verified that HMGB1 levels above 125.4 ng/mL is the cut off that distinguishes patients that are at higher risk of death. In conclusion, we propose the use of serum levels of HMGB1 as a biomarker of severe prognosis of COVID-19.