On the cell surface, HMGB1 binds to classic receptor for advanced glycation end products and Toll-like receptor 2/4/9 and then transmits danger signals to surrounding cells, thereby activating downstream signals and mediating inflammation to infection response.337,338 Severe COVID-19 is considered to involve lethal hyperinflammation with cytokine storm syndromes to resist the virus.22 HMGB1 plays a vital role in the inflammatory response of COVID-19. This evidence concerns the gene HMGB1 and infection.