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What is the association between the bitter taste receptor phenotype and outcomes after infection with SARS-CoV-2?
In this cohort study of 1935 adults, 266 tested positive for SARS-CoV-2, and those who experienced low intensity of bitter tastes or no bitter tastes (nontasters) were significantly more likely to test positive for SARS-CoV-2, to be hospitalized, and to be symptomatic for a longer duration. Conversely, those who experienced greater intensity of bitter tastes (supertasters) represented 5.6% of patients infected with SARS-CoV-2, suggesting enhanced innate immune protection.
This study suggests that bitter taste receptor allelic variants are associated with innate immune fitness toward SARS-CoV-2 and can be used to correlate with clinical course and prognosis of COVID-19.
Bitter taste receptors (T2Rs) have been implicated in sinonasal innate immunity, and genetic variation conferred by allelic variants in T2R genes is associated with variation in upper respiratory tract pathogen susceptibility, symptoms, and outcomes. Bitter taste receptor phenotype appears to be associated with the clinical course and symptom duration of SARS-CoV-2 infection.
To evaluate the association between T2R phenotype and patient clinical course after infection with SARS-CoV-2.
Design, Setting, and Participants
A prospective cohort study was performed from July 1 through September 30, 2020, at a tertiary outpatient clinical practice and inpatient hospital in the United States among 1935 participants (patients and health care workers) with occupational exposure to SARS-CoV-2.
Exposure to SARS-CoV-2.
Main Outcomes and Measures
Participants underwent T2R38 phenotype taste testing to determine whether they were supertasters (those who experienced greater intensity of bitter tastes), tasters, or nontasters (those who experienced low intensity of bitter tastes or no bitter tastes) and underwent evaluation for lack of infection with SARS-CoV-2 via polymerase chain reaction (PCR) testing and IgM and IgG testing. A group of participants was randomly selected for genotype analysis to correlate phenotype. Participants were followed up until confirmation of infection with SARS-CoV-2 via PCR testing. Phenotype of T2R38 was retested after infection with SARS-CoV-2. The results were compared with clinical course.
A total of 1935 individuals (1101 women [56.9%]; mean [SD] age, 45.5 [13.9] years) participated in the study. Results of phenotype taste testing showed that 508 (26.3%) were supertasters, 917 (47.4%) were tasters, and 510 (26.4%) were nontasters. A total of 266 participants (13.7%) had positive PCR test results for SARS-CoV-2. Of these, 55 (20.7%) required hospitalization. Symptom duration among patients with positive results ranged from 0 to 48 days. Nontasters were significantly more likely than tasters and supertasters to test positive for SARS-CoV-2 (odds ratio, 10.1 [95% CI, 5.8-17.8]; P < .001), to be hospitalized once infected (odds ratio, 3.9 [1.5-10.2]; P = .006), and to be symptomatic for a longer duration (mean [SE] duration, 23.7 [0.5] days vs 13.5 [0.4] days vs 5.0 [0.6] days; P < .001). A total of 47 of 55 patients (85.5%) with COVID-19 who required inpatient admission were nontasters. Conversely, 15 of 266 patients (5.6%) with positive PCR test results were supertasters.
Conclusions and Relevance
This cohort study suggests that T2R38 receptor allelic variants were associated with participants’ innate immune response toward SARS-CoV-2. The T2R phenotype was associated with patients’ clinical course after SARS-CoV-2 infection. Nontasters were more likely to be infected with SARS-CoV-2 than the other 2 groups, suggesting enhanced innate immune protection against SARS-CoV-2.
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CME Disclosure Statement: Unless noted, all individuals in control of content reported no relevant financial relationships. If applicable, all relevant financial relationships have been mitigated.
Accepted for Publication: March 31, 2021.
Published: May 25, 2021. doi:10.1001/jamanetworkopen.2021.11410
Open Access: This is an open access article distributed under the terms of the CC-BY License. © 2021 Barham HP et al. JAMA Network Open.
Corresponding Author: Henry P. Barham, MD, Sinus and Nasal Specialists of Louisiana, 8585 Picardy Ave, Ste 210, Baton Rouge, LA 70809 (firstname.lastname@example.org).
Author Contributions: Drs Barham and Broyles had full access to all of the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis.
Concept and design: Barham, Taha, Hall.
Acquisition, analysis, or interpretation of data: Barham, Taha, Broyles, Stevenson, Zito.
Drafting of the manuscript: Barham, Taha.
Critical revision of the manuscript for important intellectual content: All authors.
Statistical analysis: Taha, Broyles.
Administrative, technical, or material support: Barham, Taha.
Supervision: Barham, Taha, Hall.
Conflict of Interest Disclosures: Dr Barham reported having a proprietary or financial interest in the Phenomune LLC early prototype general wellness test kit used in this study and having an equity interest in Phenomune LLC whose value cannot be readily determined through reference to public prices; however, Dr Barham neither received any significant payment paid in support of his activities in this study nor did he enter into any financial arrangement whereby the outcome of this study could affect his compensation for conducting the study, in each case, in an effort to avoid potential investigator bias in this study. Dr Barham also reported having a patent for Testing Composition and Method for Determination of T2R Phenotype pending. No other disclosures were reported.
Additional Contributions: We thank Monell Chemical Senses Center, Philadelphia, Pennsylvania, for genetic analysis.
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