The mechanisms of smell loss after SARS-CoV-2 infection

The olfactory system's receptor cells are uniquely exposed to the outside environment, making them, along with other epithelial cells crucial for their function, susceptible to damage from airborne viruses, bacteria, and nanoparticles. [...]damage is cumulative and can lead to greater pathogenic epithelial vulnerability later in life.6 Environmental factors, including viruses, seem to be more important than genetic ones in relation to age-related olfactory decrements.6 Rats reared in pathogen-free environments have less age-related decline in mature olfactory neurons than rats reared in standard laboratory conditions.7 Although the olfactory epithelium can regenerate, the process of regeneration is rarely complete after severe viral infections, resulting in a patchy and thin epithelium containing islands of interspersed metaplastic squamous epithelia and fewer cilia, olfactory receptor cells, and supporting cells.8 The proportion of the roughly 6 000 000 receptor cells in the human olfactory epithelium that needs to be damaged to produce noticeable olfactory deficits is unknown. Smell loss could also reflect underlying subtle inflammation or damage to the olfactory epithelium during infection. [...]when objectively measured, some degree of smell dysfunction can remain for days after the resolution of common cold-related congestion.10 Since, unlike the common cold, COVID-19 is rarely accompanied by noticeable nasal congestion, the absence of an obvious explanation for the associated smell loss would magnify the apparent uniqueness of the loss.