English: Potential mechanism(s) for nociceptor sensitization in severe COVID-19. SARS-CoV-2 enters lung epithelial cells and resident immune cells through ACE2. In severe COVID-19 cases, IFN production is abrogated allowing the virus to replicate unrestricted. Subsequent increase in viral load further enhances the production of inflammatory mediators and leads to the development of a hyperinflammatory state known as a “cytokine storm.” Cytokines produced in the lower respiratory tract may interact with receptors on sensory nerve endings promoting neurogenic inflammation and nociceptor hypersensitivity. An exaggerated immune response leads to systemic inflammation affecting multiple organs. As such, peripheral blood mononuclear cells (PBMCs) produce potent inflammatory mediators that have known receptors in the sensory neurons and resident immune cells of the DRG, driving nociceptor sensitization. ACE2, angiotensin-converting enzyme 2; DRG, dorsal root ganglia.