Biochemical How does viral illness cause smell and taste loss? - Dr. R.I. Henkin
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The Taste and Smell Clinic

April 2018

How does viral illness cause smell and taste loss?

The most common cause of smell and taste loss is following a viral-type illness. How does this occur?

During the acute phase of a viral cold a patient may experience nasal congestion and blockage caused by nasal obstruction, membrane edema and excess nasal secretions. This congestion may cause temporary loss of smell and taste but with recovery from the cold, over time, these nasal symptoms disappear, ease of nasal breathing is resumed and smell and taste function commonly reappear as they did prior to the onset of the viral cold.

However, in about an estimated 1% of patients who experience a viral-type cold, with the recovery from the acute nasal symptoms they recognize that they have a persistent loss of smell and taste. How does this occur? Since viral colds occur in as many as 30 million patients yearly in the U.S., the loss can occur in as many as 3 million people yearly.

In an effort to understand this problem we initially attempted to culture virus in the nasal airways of patients who had recovered from their cold but had a loss of smell and taste. We were unsuccessful despite careful attempts to do so. If there were no virus present, how did this loss occur?

This question has caused much confusion for several years. What we began to hypothesize was that after recovery, which eliminated the acute systemic viral attack, there was a residual and persistent viral process affecting the protein secreting glands in the nose and mouth which caused smell and taste loss. Although the dynamics of this viral process are still unknown its mechanism of action is critical to our understanding of how smell and taste loss occur after a viral illness.

We hypothesize that a viral replication process is present in the protein secreting glands in the nose and the mouth which is sustained by a dynamic process involving continuous rounds of de novo virus infection and replication, as in (1). We hypothesize that with the initial systemic viral infection the viral RNA enters into specific protein secreting glands in the nose and mouth, replicating their genomes. These are commonly single stranded RNAs which may generate viral factories which can direct the products of proteins and construction of new viral particles which can continue to infect these glands. While the systemic viral infection is eliminated this local process can continue to generate viral RNA which is toxic to the protein secretions generated by these protein secreting glands. This toxicity can inhibit secretion of some of the endogenously secreted proteins [so-called growth factors (2)] produced by these glands. These endogenous proteins consist of multiple chemical moieties (3) including cAMP, cGMP and sonic hedgehog (4-7). Stem cells, which maintain the receptors of both olfactory epithelial cells for smell and taste bud receptor cells for taste, require continual stimulation by these secreted proteins for these receptors to function. Since these receptors turnover as rapidly as every 24 hours, inhibition of these secretions inhibits receptor growth causing loss of smell and taste (8).

  1. Wei X, Ghosh SK, Taylor ME, et al. Viral dynamics in human immunodeficiency virus type 1 infection. Nature. 1995;373:117-122.

  2. Henkin RI. Growth factors in olfaction. In: Preedy VR, Ed. The Handbook of Growth and Growth Monitoring in Health and Disease. Vol II. New York: Springer-Verlag; 2011, p. 1417-1436.

  3. Henkin RI, Martin BM. Nasal seroproteins, their physiology and pathology. Am J Rhinol. 2000;14:A-82.

  4. Henkin RI, Velicu I. cAMP and cGMP in nasal mucus: relationships to taste and smell dysfunction, gender and age. Clin Invest Med. 2008;31:E71-E77.

  5. Henkin RI, Velicu I. cAMP and cGMP in nasal mucus related to severity of smell loss in patients with smell dysfunction. Clin Invest Med. 2008;31:E78-E84.

  6. Henkin RI, Hosein S, Stateman WA, et al. Sonic hedgehog in nasal mucus is a biomarker for smell loss in patients with hyposmia. Cell Mol Med. 2016, 2:2.

  7. Henkin RI, Knöppel AB, Abdelmeguid M, et al. Sonic hedgehog is present in parotid saliva and is decreased in patients with taste dysfunction. J Oral Pathol Med. 2017;46:829-833.

  8. Henkin RI, Levy LM, Fordyce A. Taste and smell function in chronic disease: A review of clinical and biochemical evaluation of taste and smell dysfunction in over 5000 patients at The Taste and Smell Clinic in Washington, DC. Am J Otolaryngol. 2013;34:477-489.