key: cord-0964025-nvkhcyky
authors: Henkin, Robert I.
title: How does Covid-19 infection affect smell?
date: 2021-01-27
journal: Am J Otolaryngol
DOI: 10.1016/j.amjoto.2021.102912
sha: 2bbffe3e598bf413b86d4d1956c1b6346040fa95
doc_id: 964025
cord_uid: nvkhcyky

nan

Loss of smell following a viral infection was first described clinically in 1975 (2) . After a viral infection many patients report a chronic loss of smell. Indeed this patient group represents the majority among several pathological entities that cause smell loss accounting for about 25% of all patients who reported smell loss (3) . However, the type of virus which caused the smell loss was not previously determined nor was the mechanism which caused this loss (2) . In order to understand this symptom and how it is related to Covid-19 infection, a systematic evaluation of this sensory system was explored.

The smell system is comprised of three major componentsbrain, nerves and receptors.

Although each portion of this system can exhibit pathology which can inhibit smell, the major component through which pathology occurs is through pathogenesis in the olfactory receptors.

Olfactory receptors are unique since they do not contain blood vessels, lymphatics or exhibit mitosis (4). These receptors, which turn over frequently, as often as every 24 hours, depend upon stem cells which respond to growth or transcription factors secreted into nasal mucus from nasal serous glands (5) . These growth factors then activate stem cells to mature and generate the olfactory receptors by which the smell response is initiated (5) . Indeed, nasal mucus secreted J o u r n a l P r e -p r o o f from serous glands in the nasal cavity is the critical fluid through which these receptors grow and mature to maintain smell function. Indeed, failure to produce nasal mucus or salivary secretions (saliva), as occurs in Sjogren's syndrome, causes loss of sensory receptors with subsequent loss of smell and taste (6) . Restoration of these secretions is associated with the restoration of the sensory receptors and subsequent return of sensory function.

In order to understand the nature of these nasal mucus growth factors a total protein analysis of the components of nasal mucus was undertaken (7). This analysis demonstrated the presence of several moieties which can be considered as the growth factors that stimulate these stem cells.

These moieties include cyclic AMP and cGMP (8) Other studies have considered that neural factors involving the brain and the olfactory neurons themselves are responsible for the smell loss following Covid-19 infection (10) . In a recent J o u r n a l P r e -p r o o f report specific insight into the mechanism of the loss suggested that smell loss was mediated by transient dysfunction of the olfactory epithelium (11) . This observation is consistent with the mechanism presented in the present formulation.

Studies in other hyposmic patients indicate that restoration of secretion of these affected growth factors is associated with restoration of stem cell activation, olfactory receptor growth and development, and return of smell function (12). This stimulation occurs by two mutually dependent mechanismsthe action of cAMP, cGMP (7) and sonic hedgehog (8) 

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He Handbook of Growth and Growth Monitoring in Health and Disease

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