TLR4 and COVID-19: S100A12, as a marker of inflammatory disease, is overexpressed during inflammation.26 This cytokine is a TLR4 (Toll-like receptor 4) ligand and its signal transduction triggers proinflammatory activation.26 Relative to healthy controls and COVID-19 patients with non-acute necrotizing encephalopathy, significantly elevated expression of TLR4 was seen in COVID-19 acute necrotizing encephalopathy patients (Fig. 3f), particularly in inflammatory monocytes (Supplementary Fig. 4g).