The significantly elevated levels of serum HMGB1 correlated with the cytokine storm and high mortality of patients with COVID-19, indicating its potential as a predictor of clinical outcome.339 Pathologically, exogenous HMGB1 promotes the expression of ACE2, the SARS-CoV-2 entry receptor, in cultured lung epithelial cells via AGER- or AKT-dependent manner.340,341 The regulation of HMGB1 on ACE2 expression is vital for the entry of SARS-CoV-2, SARS-CoV-1, and NL63, thus affecting the susceptibility to SARS-CoV-2.342 Thus, HMGB1 is a potential biomarker and therapy target for COVID-19. The gene discussed is ACE2; the disease is COVID-19.