4 DISCUSSION
We show that COVID-19 impairs the epithelial structure and vascularization of both nasal and oral mucosa, although the nasal mucosa seems to be altered to a less extent than the oral mucosa is. We suggest that COVID-19 may cause multiple cranial neuropathies of quite varying degree (i.e. mild to profound) involving the nerves responsible for the innervation of fPap and the transmission of the chemical stimuli. Most patients reported a concomitant loss of smell and taste, and fewer patients reported only loss of either smell or taste [15,17]. 65.71 % of the patients reported a total recovery of both taste and olfaction within 4 weeks after the discharge from the hospital, and 74.29 % had recovered within 6 weeks after hospital discharge (both olfactory and gustatory function). However, the reported recovery time (median: 17 days) was not as short as reported in previous studies, probably because the hospitalized patients included in our study had more severe disease [17].
A significant study limitation is the lack of objective data on taste and olfaction in the study participants before hospitalization and even before the infection. Although all participants reported no history of gustatory or olfactory disorder in the past, any objective measurements to compare are missing. Another limitation is the lack of subjective methods for the evaluation of gustatory function. In our study electrogustometry was preferred, because of its reliability and the ability to take repeated results on the same loci. It should be mentioned that the control group was not measured twice, as these subjects remained healthy throughout the study the study, without corresponding pneumonia or any other medication.
The nasal cavity plays an important role in COVID-19 infection; it is probably the major entry point for SARS-CoV-2 and the site of intense viral replication [17,18]. SARS-CoV-2 seems to have its own mechanisms of aggression to the olfactory neuroepithelium, with a greater predilection for neural structures’ involvement over the nasal mucosa [19]. Subjective olfactory dysfunction in COVID-19 patients has been extensively reported in a number of studies [1,4,8-9].
The exact mechanisms underlying olfactory and gustatory disorders among patients with COVID-19 infection remain unclear. SARS-C0V-2 seems to enter the central nervous system (CNS) via the olfactory or trigeminal route. Initially, the CNS infection or inflammation could be mild and cause olfactory damage [23-25]. However, olfactory impairment after upper respiratory tract infection is a common occurrence in clinical settings [21-24]. Another hypothesis is that COVID-19 infection could be related to the involvement of the olfactory bulb or to peripheral damage of the olfactory receptor cells in the nasal neuroepithelium. This assumption is based on the potential neurotrophic features of SARS-CoV-2 [17,18].
The role of innervation in the regeneration of the fungiform papillae has been extensively studied. The impact of denervation on fungiform taste buds appears to be less severe than on circumvallate; while the former are reduced in number, many albeit smaller taste buds remain [21,24]. Differentiated taste buds disappear or are reduced in density in denervated taste epithelium. Progenitor taste cells also require the trophic and / or electrical signals provided by the afferent taste nerve fibres, in order to continue to provide immature taste cells to the taste buds [24,25].