The COVOSMIA-19 trial: Preliminary application of the Singapore smell and taste test to objectively measure smell and taste function with COVID-19

The COVOSMIA-19 trial: Preliminary application of the Singapore smell and taste test to objectively measure smell and taste function with COVID-19

Abstract

Sudden loss of smell and/or taste has been identified as an early symptom of SARS-CoV-2 2019 (COVID-19) infection, and presents an effective target for prompt self-isolation and reducing community spread. The current study sought to develop and test a novel, rapid, self-administered test to objectively measure smell and taste losses associated with COVID-19, and administered self-report questionnaires to characterize symptoms associated with COVID-19 in Singapore. Participants (N = 99) completed questionnaires to record recent changes in smell and taste ability. This was followed by the ‘Singapore Smell and Taste Test’ (SSTT), a personal, objective testing kit for daily self-assessment of smell and taste function at their place of residence. Seventy-two recruited participants were confirmed as COVID-19 positive at baseline, of which 58 completed the SSTT at home. Of these, 36.2% had objectively measured smell and/or taste loss. The SSTT measures of smell and taste function were positively associated with participants’ self-reported smell and taste acuity, and rated smell intensity of 6 common household items. This study presents the first application of the SSTT as a rapid, cost-effective, objective tool to self-monitor smell and taste function in a residential setting, and ensures comparability across individuals through the use of standardized stimuli. The SSTT has potential for future application in populations with limited access to formal COVID-19 testing as a self-administered objective method to monitor sudden changes in smell and taste, and to prompt early self-isolation, in order to reduce community transmission of COVID-19.

Abbreviations
COVID-19Coronavirus disease 2019SARS-CoV-2Severe Acute Respiratory Syndrome Coronavirus 2PCRPolymerase Chain ReactionSSTTThe Singapore Smell and Taste TestSSTQThe Singapore Smell and Taste QuestionnaireSNOT-2222-item Sino-Nasal Outcome testVASVisual Analogue Scale


Keywords
SARS-CoV-2COVID-19Olfactory dysfunctionGustatory dysfunctionAnosmiaAgeusia

 

1. Introduction
Sudden loss of smell (anosmia) and/or taste (ageusia) are now globally recognised as key symptoms of Severe Acute Respiratory Syndrome Coronavirus 2 infection (SARS-CoV-2) (causing the disease known as COVID-19) (American Academy of Otolaryngology-Head and Neck Surgery, 2020, ENT UK, 2020b, ENT UK., 2020a, European Rhinologic Society, 2020, Alert, 2020, Gane et al., 2020, Menni et al., 2020, Pellegrino et al., 2020), alongside fever, dry cough, fatigue and breathing difficulties (World Health Organisation, 2020). Many global public health bodies, including the Singapore Ministry of Health (2020), recommend that individuals at risk monitor their sense of smell and taste, and self-isolate and present for formal diagnostic testing should they experience any sudden changes (American Academy of Otolaryngology-Head and Neck Surgery, 2020, Centers for Disease Control and Prevention, 2020, ENT UK, 2020b, ENT UK., 2020a, Public Health England, 2020, World Health Organisation, 2020).

Data from self-report questionnaires collected across many countries and clinical populations demonstrate an association between sudden onset smell and/or taste loss and SARS-CoV-2 infection (Bagheri et al., 2020, Klopfenstein et al., 2020, Lechien, Chiesa-Estomba et al., 2020, Lechien, Chiesa-Estomba, Hans et al., 2020, Parma et al., 2020, Yan et al., 2020). Self-report questionnaire measures are often used because they are cost-effective and easy to implement at a large scale, but they can also be subjective, and prone to biases and inaccuracies. In particular, self-report measures of smell and taste often rely on individuals noticing these changes, which may result in under-reporting and not accurately reflect the prevalence of these symptoms. This is likely because the relationship between self-reported and objectively measured sensory function is typically low (Landis et al., 2003). A recent meta-analysis highlighted the need for objective sensory testing with standardised stimuli to identify and track COVID-19-related changes (Hannum et al., 2020).

This has been confirmed by a handful of studies that have objectively measured smell and taste changes using formal tests (Altin et al., 2020, Hintschich et al., 2020, Hornuss et al., 2020, Iravani et al., 2020, Lechien, Cabaraux et al., 2020, Lechien, Ducarme et al., 2020, Moein et al., 2020, Vaira, Deiana et al., 2020, Vaira, Hopkins et al., 2020, Vaira, Salzano et al., 2020, Villerabel et al., 2021). Recent meta-analyses report a considerable proportion of smell and taste disorders among individuals with COVID-19 (Agyeman et al., 2020, Rocke et al., 2020, Tong et al., 2020). Borsetto et al. (2020) reported an overall prevalence of 47% for changes in smell and taste, with 31% and 67% in severe and mild-to-moderate symptomatic patients respectively. As well as a high prevalence, particularly in milder cases (Aziz et al., 2020), smell and/or taste loss often occur early, sometimes presenting as the first symptom or the only symptom in otherwise asymptomatic individuals (Beltrán-Corbellini et al., 2020, Borsetto et al., 2020, Haehner et al., 2020, Hopkins et al., 2020, Iacobucci, 2020, Karimi-Galougahi et al., 2020, Kaye et al., 2020, Lee et al., 2020, Vukkadala et al., 2020). The onset of smell and/or taste loss is often sudden and, unlike other upper respiratory tract infections, frequently occurs in the absence of nasal obstruction (Gane et al., 2020, Gengler et al., 2020, Lechien, Chiesa-Estomba, Hans et al., 2020). Sudden smell and/or taste loss presents as a key symptom of COVID-19 that could prompt rapid self-isolation in otherwise asymptomatic individuals, who may risk unintentional spreading of the virus without exhibiting some of the more pronounced symptoms, such as dry cough or fever.

The available evidence on self-reported smell and taste loss with COVID-19 highlights wide variation in the prevalence of these symptoms, with values ranging from 3 to 98% for smell loss and from 6 to 63% for taste loss with SARS-CoV-2 infection depending on the population under study (Agyeman et al., 2020). Data from a retrospective review of medical records demonstrates lower prevalence numbers compared to the majority of self-report studies (Pellegrino et al., 2020). Furthermore, Hajikhani et al. (2020) reported that decreased sense of smell (hyposmia), and decreased (hypogeusia) or distorted (dysgeusia) sense of taste were more common than complete loss of smell (anosmia), and this gradation of symptoms may further explain the heterogeneity of recent findings. Although individuals may notice a sudden and complete loss of smell and/or taste, they may be less aware of subtler reductions in sensitivity over time. In this respect, objective measures of smell and taste sensitivity may be more accurate in identifying changes related to COVID-19, with pooled prevalence estimates of smell loss of 77% and 45% when measured through objective and subjective methods respectively (Hannum et al., 2020).

Recent findings from formal smell testing with the University of Pennsylvania Smell Identification Test (UPSIT) revealed that 98% of COVID-19 positive participants exhibited some smell dysfunction, with 25% presenting with anosmia and 73% with severe to mild olfactory dysfunction (Moein et al., 2020). The UPSIT and other traditional objective smell and taste tests are designed to provide a formal clinical diagnosis of sensory (dys)function. Hence, they are often time-consuming to administer and require delivery or instruction by a medical professional, making them impractical for widespread application of self-administered monitoring in a community setting. In addition, many of these approaches utilise test stimuli that are designed for repeated use, and become expensive when used only once in an effort to reduce cross-infection between subjects. Current social distancing requirements also restrict access to COVID-19 patients and require objective sensory tests to be self-administered with remote data collection. Although a formal clinical diagnosis with a Polymerase Chain Reaction (PCR) swab test is still necessary to confirm SARS-CoV-2 infection, early self-isolation is key to limiting the spread of the infection, and could be supported by a rapid, cost-effective, self-administered screening test with standardised stimuli for those who may not have immediate access to formal swab tests.

The current study sought to develop and test a novel, rapid, self-administered test, the Singapore Smell and Taste Test (SSTT), to objectively measure smell and taste losses associated with COVID-19. We aimed to create a brief testing procedure that could be easily administered in the home with minimal cost and participant burden. In the wake of the COVID-19 pandemic, and the pressing need to investigate smell and taste losses in COVID-19 populations, other home testing procedures utilising household items as items in a smell and taste test have been developed (Iravani et al., 2020, Vaira, Salzano et al., 2020). In the current situation, where traditional, expensive, clinically-administered smell and taste tests are impractical for use with restricted-access patients and in times of social distancing, these present a test than anyone can feasibly do, providing they have some of the specific household ingredients. However, we sought to further reduce the participant burden and time to complete our test by providing individuals with standardised stimuli in a testing kit. In addition, this reduces the risk of introducing unwanted stimuli variation or problems for comparability of smell and taste loss across individuals that can occur when participants are required to source and prepare their own test stimuli. With the SSTT, we present a method to assess smell/taste loss across individuals in a comparable way, with minimal participant burden and easy administration.

Thus, the current study presents the first application of the SSTT to objectively measure changes in smell and taste sensitivity, and compares responses to self-reported changes in sensory acuity using questionnaire approaches in the same participants.

 

2. Methods
2.1. Study design
In the current study, participants were asked to report on changes to their smell and taste sensitivity, and the onset of any changes, in the two previous weeks via a series of self-report questionnaires, and thereafter to prospectively track daily changes in smell and taste acuity using an objective self-assessment test. This self-assessment test objectively measured smell and taste acuity. The trial was registered at ClinicalTrials.gov (Ref: NCT04492904) and the study obtained ethical approval from the National Healthcare Group Domain Specific Review Board (DSRB) (Ref: 2020/00810). The study design, measures, and protocol are outlined fully in Sheen et al. (2020).

2.2. Recruitment procedure
Participants were recruited from patients attending COVID-19 screening at the National University Hospital (NUH) and individuals from a Community Care Facility (CCF) who had been referred for a PCR test following suspected COVID-19, or who had tested COVID-19 positive on the day of recruitment into the study. As such, ‘Day 0′ represents the day that each participant underwent the PCR test and consented to participate. To confirm whether these individuals suspected of COVID-19 infection were positive, Nasal Swab PCR test results were confirmed for each participant via one-time access to their medical records. A small portion were identified as COVID-19 negative (see Fig. 1).

Reference: https://www.sciencedirect.com/science/article/pii/S0950329321003645

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