Human Type II Taste Cells Express Angiotensin-Converting Enzyme 2 and Are Infected by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2)

Abstract

Chemosensory changes are well-reported symptoms of SARS-CoV-2 infection. The virus targets cells for entry by binding of its spike protein to cell-surface angiotensin-converting enzyme- 2 (ACE2). It was not known whether ACE2 is expressed on taste receptor cells (TRCs) nor if TRCs are infected directly. Using an in-situ hybridization (ISH) probe and an antibody specific to ACE2, ACE2 is present on a subpopulation of TRCs, namely, Type II cells in taste buds in taste papillae. Fungiform papillae (FP) of a SARS-CoV-2+ patient exhibiting symptoms of COVID-19, including taste changes, were biopsied. Based on ISH, replicating SARS-CoV-2 was present in Type II cells. Therefore, taste Type II cells provide a potential portal for viral entry that predicts vulnerabilities to SARS-CoV-2 in the oral cavity. The continuity and cell turnover of the patient’s FP taste stem cell layer were disrupted during infection and had not completely recovered 6 weeks post symptom onset. Another patient suffering post-COVID-19 taste disturbances also had disrupted stem cells. These results demonstrate the possibility that novel and sudden taste changes frequently reported in COVID-19 may be the result of direct infection of taste papillae by SARS-CoV-2. This may result in impaired taste receptor stem cell activity and suggest more work is needed to understand the acute and post-acute dynamics of viral kinetics in the human taste bud.

Longitudinal trajectories and determinants of human fungiform papillae density

“…As potential endocrine organs, fungiform papillae may provide us with a new window into human physiology that is easily accessible and observable, one that could be utilized in biopsy for further testing and examination. Along those lines, we have recently reported that SARS-CoV-2 infect taste receptor cells in taste buds of biopsied fungiform papillae [ 56 ]. With all these relevant areas of research in mind, we have developed an in vivo model and mechanistic studies are currently underway to study age-related and SARS-CoV-2 related taste loss or changes.…”

Comprehensive Chemosensory Psychophysical Evaluation of Self-reported Gustatory Dysfunction in Patients With Long-term COVID-19

“…1,2 A substantial body of evidence has demonstrated the effect of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) on olfaction, 3 although few observations exist regarding a direct involvement of the virus in the pathogenesis of gustatory impairment. 4 While the correlation between self-reported olfactory function and psychophysical tests has been extensively analyzed, showing poor agreement between the 2 types of evaluation, no robust data exist concerning the gustatory function. 5 To establish whether psychophysical tests confirm a self-reported alteration of taste, we assessed a series of patients selfreporting a persistent distorted perception of basic tastes after COVID-19 using a comprehensive gustatory and olfactory psychophysical evaluation.…”

Potential pharmacologic treatments for COVID-19 smell and taste loss: A comprehensive review

“…It has been shown that the taste buds and salivary glands have a high number of ACE2 receptors ( Doyle et al, 2021 ; Song et al, 2020 ). Furthermore, the essential role of the renin-angiotensin-aldosterone system (RAAS) in the perception of flavors has been confirmed previously.…”