Importance: Sudden smell loss is a specific early symptom of COVID-19, with an estimated prevalence of ~40% to 75%. Smell impairment affects physical and mental health, and dietary behavior. Thus, it is critical to understand the rate and time course of smell recovery. Objective: To characterize smell function and recovery up to 11 months post COVID-19 infection. Settings, Participants: This longitudinal survey of individuals suffering COVID-19-related smell loss assessed disease symptoms and gustatory and olfactory function. Participants (n=12,313) who completed an initial respiratory symptoms, chemosensory function, and COVID-19 diagnosis survey (S1) between April and September 2020 and completed a follow-up survey (S2) between September 2020 and February 2021; 27.5% participants responded (n=3,386), with 1,468 being diagnosed with COVID-19 and suffering co-occurring smell and taste loss at the beginning of their illness. Main Outcomes & Measures: Primary outcomes are ratings of smell and taste function on a visual analog scale, and self-report of parosmia (smell distortions) and phantosmia (unexplained smells). Secondary outcomes include a checklist of other COVID-19 symptoms. Results: On follow-up (median time since COVID-19 onset ~200 days), ~60% of women and ~48% of men reported less than 80% of their pre-illness smell ability. Taste typically recovered faster than smell, and taste loss rarely persisted if smell recovered. Prevalence of parosmia and phantosmia was ~10% of participants in S1 and increased substantially in S2: ~47% for parosmia and ~25% for phantosmia. Persistent smell impairment was associated with more symptoms overall, suggesting it may be a key marker of long-COVID. During COVID-19 illness, the ability to smell was slightly lower among those who did not recover their pre-illness ability to smell at S2. Conclusions and Relevance: While smell loss improves for many individuals who lost it due to COVID-19, the prevalence of parosmia and phantosmia increases substantially over time. Olfactory dysfunction is also associated with wider COVID-19 symptoms and may persist for many months after COVID-19 onset. Taste loss in the absence of smell loss is rare. Persistent qualitative smell symptoms are emerging as common long-term sequelae; more research into treatment options is strongly warranted given that conservative estimates suggest millions of individuals may experience parosmia following COVID-19. Healthcare providers worldwide need to be prepared to treat post COVID-19 secondary effects on physical and mental health.

Taste dysfunctions may occur, for example, after viral infection, surgery, medications, or with age. In clinical practice, it is important to assess patients’ taste function with rapidity and reliability. This study aimed to develop a test that assesses human gustatory sensitivity together with somatosensory functions of astringency and spiciness. A total of 154 healthy subjects and 51 patients with chemosensory dysfunction rated their gustatory sensitivity. They underwent a whole-mouth identification test of 12 filter-paper strips impregnated with low and high concentrations of sweet, sour, salty, bitter (sucrose, citric acid, NaCl, quinine), astringency (tannin), and spiciness (capsaicin). The percentage of correct identifications for high-concentrated sweet and sour, and for low-concentrated salty, bitter and spicy was lower in patients as compared with healthy participants. Interestingly, a lower identification in patients for both astringent concentrations was found. Based on the results, we proposed the Seven-iTT to assess chemo/somatosensory function, with a cut-off of 6 out of 7. The test score discriminated patients from healthy controls and showed gender differences among healthy controls. This quantitative test seems to be suitable for routine clinical assessment of gustatory and trigeminal function. It also provides new evidence on the mutual interaction between the two sensory systems.

Gustatory ability is an important marker of health status, including COVID-19 disease. We compare self-reporting with home and lab psychophysical "taste strips" tests in healthy subjects. The taste test consisted of paper strips impregnated with sweet, bitter, salty, or sour tastants, and with the trigeminal stimulus capsaicin, each in high and in low concentration. The test was carried out either in a controlled lab environment (74 participants, 47 women) with the strips being administered by the experimenter or self-administered by the participants at home (77 participants, 59 women). After self-reporting their subjective assessment of chemosensory ability, the participant identified the taste of each strip and rated intensity and pleasantness. Identification score, intensity, and pleasantness averaged over the 8 taste strips were similar between the lab and the home-administered tests. Self-rated taste ability did not correlate with any of these scores, but strongly correlated with self-rated smell ability in the lab group (r=0.73), and moderately correlated in the home group (r=0.51). Taste identification correlated with intensity ratings (r=0.63 lab, r=0.36 home) but not with the pleasantness ratings (r=-0.14 lab, r=0.1 home). The results of the taste strips test were similar in the lab and at home for healthy young participants and provide a baseline against which taste tests can be compared in future applications.

The gustatory, olfactory, and trigeminal systems are anatomically separated. However, they interact cognitively to give rise to oral perception, which can significantly affect health and quality of life. We built a Supervised Learning (SL) regression model that, exploiting subjects’ features, was capable of automatically analyzing with high precision the self-ratings of oral sensitivity of healthy participants and patients with chemosensory loss, determining the contribution of its three components: gustatory, olfactory, and trigeminal. CatBoost regressor provided predicted values of the self-rated oral sensitivity close to experimental values. Patients showed lower predicted values of oral sensitivity, lower scores for measured taste, spiciness, astringency, and smell sensitivity, higher BMI, and lower levels of well-being. CatBoost regressor defined the impact of the single components of oral perception in the two groups. The trigeminal component was the most significant, though astringency and spiciness provided similar contributions in controls, while astringency was most important in patients. Taste was more important in controls while smell was the least important in both groups. Identification of the significance of the oral perception components and the differences found between the two groups provide important information to allow for more targeted examinations supporting both patients and healthcare professionals in clinical practice.

In healthy humans, taste sensitivity varies widely, influencing food selection and nutritional status. Chemosensory reductions have been associated with numerous pathological disorders or pharmacological interventions. Reliable psychophysical methods are crucial resources to analyze the taste function during routine clinical assessment. However, in the daily clinical routine, they are often considered to be too time-consuming. We used the Supervised Learning (SL) regression method to analyze with high precision the overall taste status of healthy controls (HC) and patients with chemosensory loss and to characterize the combination of responses that best can predict the overall taste status of two groups. Random Forest regressor allowed us to achieve our objective. The analysis of the order of importance and impact of each parameter on the prediction of overall taste status in the two groups showed that salty (low concentration) and sour (high concentration) stimuli specifically characterized healthy subjects, while bitter (high concentration) and astringent (high concentration) stimuli identified patients with chemosensory loss. The identification of these distinctions appears to be of interest to the health system since they may allow the use of specific stimuli during routine clinical assessments of taste function reducing the commitment in terms of time and costs.