HMGB1 and COVID-19: Consistent with this, elevated HIF-1α signaling is seen in patients with severe COVID-19 experiencing low levels of oxygen in affected tissues and blood, and HMGB1 activates HIF-1α to promote pro-inflammatory cytokine production via NF-κB in activated monocytes under hypoxic condition (Peng et al., 2021; Figure 4F).