Expression of ACE2 and TMPRSS2 Proteins in the Upper and Lower Aerodigestive Tracts of Rats: Implications on COVID 19 Infections

Abstract

Objective Patients with coronavirus disease 2019 (COVID‐19), caused by severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2), exhibit not only respiratory symptoms but also symptoms of chemo‐sensitive disorders. Cellular entry of SARS‐CoV‐2 depends on the binding of its spike protein to a cellular receptor named angiotensin‐converting enzyme 2 (ACE2), and the subsequent spike protein‐priming by host cell proteases, including transmembrane protease serine 2 (TMPRSS2). Thus, high expression of ACE2 and TMPRSS2 is considered to enhance the invading capacity of SARS‐CoV‐2. Methods To elucidate the underlying histological mechanisms of the aerodigestive disorders caused by SARS‐CoV‐2, we investigated the expression of ACE2 and TMPRSS2 proteins using immunohistochemistry, in the aerodigestive tracts of the tongue, hard palate with partial nasal tissue, larynx with hypopharynx, trachea, esophagus, and lung of rats. Results Co‐expression of ACE2 and TMPRSS2 proteins was observed in the taste buds of the tongue, nasal epithelium, trachea, bronchioles, and alveoli with varying degrees of expression. Remarkably, TMPRSS2 expression was more distinct in the peripheral alveoli than in the central alveoli. These results coincide with the reported clinical symptoms of COVID‐19, such as the loss of taste, loss of olfaction, and respiratory dysfunction. Conclusions A wide range of organs have been speculated to be affected by SARS‐CoV‐2 depending on the expression levels of ACE2 and TMPRSS2. Differential distribution of TMPRSS2 in the lung indicated the COVID‐19 symptoms to possibly be exacerbated by TMPRSS2 expression. This study might provide potential clues for further investigation of the pathogenesis of COVID‐19. Level of Evidence NA Laryngoscope, 131:E932–E939, 2021

Oral Symptoms Associated with COVID-19 and Their Pathogenic Mechanisms: A Literature Review

“…They also confirmed that ACE2 is expressed in human oral tissues, especially enriched in dorsal tongue more than gingival and buccal tissues. Sato et al [ 149 ] found that ACE2 and TMPRSS2 responsible for the viral cellular entry are co-expressed in the taste buds of tongue foliate papillae of rats. Wang et al [ 150 ] revealed that ACE2 is enriched in a subpopulation of mouse tongue epithelial cells.…”

Neurological pathogenesis of SARS-CoV-2 (COVID-19): from virological features to clinical symptoms

“…Most patients with these disorders recover in 14 days, but some patients remain symptomatic for longer periods [52]. ACE2 may be expressed in the taste buds [53], and these long-lasting disorders may be directly affected by the virus.…”

Covid-19, Anosmia, Ageusia: Prospective Observational Study, Follow-Up Three and Eight Months Later

“…Viral entry needs viral protease activity, mainly transmembrane protease serine 2 (TMPRSS2) or eventually cathepsin B/L. ACE2 is present on the surface of endothelial cells, and many other cells in the lower (lung) and upper respiratory tract (nasal epithelium), heart, brain, intestines, liver, kidneys, testicles, cornea and salivary glands [3]. Infection ranges from asymptomatic to mild (about 50% of infected subjects), moderate, or severe.…”

“…The most common symptoms of COVID-19 are fever, Copyright © Yordan Benhamou GMR.000615. 5 (3).2021 chills, dry cough, dyspnea, diarrhea, headache, unusual fatigue, alteration of the general state. Sudden loss of smell (anosmia) or taste (ageusia) occurs in approximately 60% of mild to moderated forms of COVID-19, and regresses within a few weeks [5][6][7].…”

“…Taste is conveyed by taste buds, which are present mainly on the tongue then by the soft palate, pharynx and other oro-pharyngeal mucous membranes. Co-expression of ACE2 and TMPRSS2 proteins in taste buds is controversial [3,14]. Taste buds contain gustatory neurons, support cells and basal cells.…”