key: cord-0766433-awoaa42p
authors: Barham, Henry P.; Taha, Mohamed A.; Hall, Christian A.
title: Does phenotypic expression of bitter taste receptor T2R38 show association with COVID‐19 severity?
date: 2020-08-27
journal: Int Forum Allergy Rhinol
DOI: 10.1002/alr.22692
sha: 7007eab9ef844c5b81e07eee854d0217aec7d958
doc_id: 766433
cord_uid: awoaa42p

INTRODUCTION: SARS‐CoV‐2 has been identified as the pathogen causing the outbreak of Coronavirus Disease 2019(COVID‐19) commencing in Wuhan, China, in December 2019. Multiple reports have shown subjective loss of taste and smell as an early and hallmark symptom for COVID‐19. METHOD: A retrospective study was performed in our clinical practice during July 2020 on patients positive for SARS‐CoV‐2 via PCR. All patients were categorized into 3 groups (supertasters, tasters, & nontasters) via taste sensitivity to phenylthiocarbamide, thiourea, and sodium benzoate with taste strip testing. The results of the taste strip tests were correlated with clinical course. RESULTS: 100 patients (mean 51 [Range 24‐82] years of age; 44 [44%] female) were assessed. Our results showed that 21/100 (21%) were non‐tasters, 79/100 (79%) were tasters, and 0/100 (0%) were supertasters (p<0.001). 21/21 (100%) (p<0.001) of the patients requiring inpatient admission were classified as non‐tasters. 79/79 (100%) (p<0.001) of the patients who displayed mild to moderate symptoms not requiring admission were classified as tasters. CONCLUSION: Our results show objective data that taste disturbance, specifically global loss of taste, appears to correlate with the clinical course specific to each individual because 100% of the patients requiring inpatient admission were classified as non‐tasters. This article is protected by copyright. All rights reserved

Our retrospective cross-sectional study provides evidence that phenotypic expression of bitter taste receptor isoform 38 (T2R38) with taste strip testing appears to show association with clinical course of severe acute respiratory syndrome associated coronavirus-2 (SARS-CoV-2).

A cluster of viral pneumonia cases associated with a novel SARS-CoV-2 was first identified in Wuhan, China, in December 2019 and has rapidly spread around the world, causing a global health crisis. The disease was subsequently named COVID-19 by the World Health Organization and has been declared a pandemic on March 11, 2020. While the social distancing measures can be effective, strict adherence and enforcement of these measures is proving to be difficult for society at large.

In the airway, bitter taste receptors (T2R) have been found to participate in innate immunity and are present on a variety of cell types including ciliated sinonasal epithelial cells, which are a first line of defense in upper airway immunity. Effective mucociliary clearance (MCC) requires coordinated ciliary driven movement of airway surface liquid, composed of mucustrapped pathogens and debris, to maintain a healthy sinonasal tract. When MCC is impaired, stasis of secretions and resultant inflammation occur, and can be inciting factors in increasing susceptibility to infections. Beyond their role in MCC, ciliated airway cells also function as a source of antimicrobial compounds (1).

Solitary chemosensory cells (SCCs) are non-ciliated epithelial cells that also express T2R. Taste receptor expression on SCCs was first detected in mouse nasal mucosa. Stimulation of murine SCCs by bitter or sweet ligands elicited acetylcholine-mediated stimulation of the trigeminal nerve with resultant protective reflexes including decreased respiratory rate, presumably to decrease inspiration of airborne pathogens, and the release of antimicrobial peptides (2, 3) . In humans, SCCs are present approximately 1 in every 100 epithelial cells in the sinonasal cavity (4).

Bitter taste receptors are known to be a G-protein coupled receptor and plays an important role in innate immunity through inducing the release of nitric oxide (via ciliated epithelial cells) and promoting secretion of antimicrobial peptides (via SCC) for the effective elimination of the invading pathogens. Bitter taste receptor T2R38 is an isoform of T2R and can exist with different polymorphisms as PAV/PAV (supertaster), PAV/AVI (taster), & AVI/AVI (non-tasters). Those homozygous for functional T2R38 (PAV/PAV) are known to have fewer gram-negative upper respiratory infections and report higher quality of life when compared to those heterozygous (PAV/AVI) and homozygous for non-functional (AVI/AVI) (1).

Phenotypic expression of T2R38 can be tested by using phenylthiocarbamide (PTC) paper taste strips. Those with homozygotic functioning allele (PAV/PAV) can taste intensely bitter elements on the test strip while those with homozygotic non-functioning (AVI/AVI) taste nothing. Heterozygotes (PAV/AVI) can taste a range of flavors but do not perceive bitterness as intense as those with the homozygous functioning allele.

We assessed a potential association between phenotypic expression of T2R38 and outcome of COVID-19, with special attention to clinical course requiring hospitalization. We stratified patients into more and less severe clinical course of disease according to need for hospitalization during infection. Those patients requiring hospitalization for treatment comprise the more severe cohort. All patients underwent evaluation with taste strip test to evaluate phenotypic expression of T2R38.These taste strips (litmus paper) included control (chemical free), PTC, Thiourea and Sodium Benzoate. All patients were categorized into 3 groups (supertasters, tasters, & non-tasters). Statistical analyses were performed using SPSS v 22 (SPSS Statistics for Windows, version 22.0; IBM, Armonk, NY). Descriptive data are presented as percentages and means ± standard deviation (SD). global chi-squared and logistic regression was used for nominal variables. Results were deemed significant with a p value of <0.05.

We performed a retrospective cross-sectional analysis evaluating 100 adult patients (mean [SD] 51 [15.81] years of age; 44 [44%] female) who have tested positive for SARS-CoV-2 via polymerase chain reaction (PCR) using nasal swab who were managed in our medical practice in July 2020. In our study, 21 patients (21%) required hospitalization and 79 patients (79%) displayed mild to moderate symptoms not requiring admission but underwent home quarantine with symptomatic treatment. The results showed that 21 patients (21%) were non-tasters (none), 79 patients (79%) were tasters (moderate), and 0 patients (0%) were supertasters (intense) (p<0.001). (Figure 1) All 21 patients (100%) requiring hospitalization were classified as non-tasters, while 79/79 (100%) of the patients who displayed mild to moderate symptoms not requiring admission were classified as tasters (p<0.001).

Interestingly, taste strip testing appears to be associated with severity of clinical course as 100% of the patients requiring inpatient admission were classified as non-tasters. Of note, supertasters represented 0% of our patient population testing positive to the presence of SARS-CoV-2 via PCR.

Confounding factors are inherent in this retrospective study with known patient outcomes. Our study is limited by lack of genetic testing, so we were unable to correlate the genotype with phenotypic expression of T2R38. Another limitation is that no testing for phenotype expression was performed prior to COVID infection, so we are unclear if phenotypic expression of T2R38 can predict clinical severity of COVID-19 infection or if phenotypic expression of T2R38 is a consequence of COVID infection severity.

Phenotypic expression of T2R38 with taste strip testing appears to associate with the clinical course and symptomatology specific to each individual as 100% of the patients requiring inpatient admission were classified as non-tasters. Conversely, supertasters represented 0% of our patient population, suggesting the possibility of innate immunity to SARS-CoV-2. This is a relevant point of study and deserves further evaluation in the context of COVID-19 given the possibility of a finding of absence rather than an absence of findings and suggests the possibility of either innate immunity to SARS-CoV-2 or the effect of SARS-CoV-2 on T2R38 bitter taste receptor. 

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Solitary chemosensory cells and bitter taste receptor signaling in human sinonasal mucosa