**2. Pathophysiolgy**

Coronaviruses are known to cause odor loss from previous studies [13]. However, the pathophysiological mechanism of COVID-19 that causes odor and taste disorders has not been fully clarified yet.

## **2.1 Pathophysiolgy of gustatory dysfunction**

In humans, the sense of taste is carried by three cranial nerves. Facial nerve (7th cranial nerve), glossopharyngeal nerve (9th cranial nerve) and vagus (10th cranial nerve). When the terminal branches are stimulated, the sense of taste reaches to the nucleus solitarius in the brainstem and then it is carried to the thalamus. Hypogeusia can develop through the involvement of one of these three nerves, the nucleus solitarius or tract, or any of the thalamus nuclei. Angiotensin-Converting Enzyme 2 (ACE2) receptors, which allow SARS-CoV-2 to attach to the tissue, are widely expressed in the mucous membrane of the entire oral cavity, especially in the tongue [14–16]. The role of ACE2 in modulating taste perception has been emphasized in many studies analyzing the chemosensitive side effects of ACE2 inhibitors and angiotensin II blockers [16, 17]. Taste disturbance usually regresses after cessation of treatment. Also, a condition recently identified for SARS-CoV-2 is that it can bind to sialic acid receptors [18]. Sialic acid is an essential component of saliva mucin and protects glycoproteins that transport taste molecules into taste pores from early enzymatic degradation [16]. A decrease in sialic acid in saliva is associated with an increase in the threshold of taste [19]. Although it has been suggested that the deterioration in the perception of smell may also cause the loss of taste function due to the close functional link between these two chemosensory systems, the sense of taste seems to be more affected in recent publications.
