Fig. 3.

Persistent inflammation, hypoxia, and sympathetic overactivation can result in autonomic dysfunction in long COVID. The activation of the innate immune cells following SARS-CoV-2 infection results in a cytokine storm characterized by the great release of interleukins and chemokines. As more leukocytes migrate to the site of infection, more oxygen is consumed leading to a hypoxic state. The decrease in oxygen supply in the affected tissues promotes hypoxia by inhibiting PHD and allowing the activation of HIF-1α and NF-κB, a master inducer of inflammation. This positive loop promotes SNS overactivation that can eventually induce neuroinflammation and cell death. Abbreviations: PHD: Prolylhydroxylase; NF-κB: nuclear factor kappa B; HIF-1α: hypoxia inducible factor 1 alpha; SNS: sympathetic nervous system.