Olfactory dysfunction in COVID-19: new insights into the underlying mechanisms

The mechanisms of olfactory dysfunction in COVID-19 are still unclear. In this review, we examine potential mechanisms that may explain why the sense of smell is lost or altered. Among the current hypotheses, the most plausible is that death of infected support cells in the olfactory epithelium causes, besides altered composition of the mucus, retraction of the cilia on olfactory receptor neurons, possibly because of the lack of support cell-derived glucose in the mucus, which powers olfactory signal transduction within the cilia. This mechanism is consistent with the rapid loss of smell with COVID-19, and its rapid recovery after the regeneration of support cells. Host immune responses that cause downregulation of genes involved in olfactory signal transduction occur too late to trigger anosmia, but may contribute to the duration of the olfactory dysfunction.