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ImportanceSudden 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.ObjectiveTo characterize smell function and recovery up to 11 months post COVID-19 infection.Settings, ParticipantsThis 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 & MeasuresPrimary 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.ResultsOn 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 RelevanceWhile 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.Trial registrationThis project was pre-registered at OSF: https://osf.io/3e6zc.Graphical abstractKey PointsQuestionWhat are the characteristics of smell and taste recovery of COVID-19 patients?FindingsIn this preregistered observational study of 1,468 participants, smell loss is associated with a higher number of COVID-19 symptoms, and may persist for at least 11 months following disease onset. While a majority of participants report quantitative improvement in their ability to smell, the prevalence of parosmia and phantosmia increases substantially at follow-up. Taste recovers faster than smell, suggesting taste and smell recover separately and can be distinguished by the respondents.MeaningOlfactory dysfunction appears to be a component of long-COVID, with parosmia as a prominent symptom in almost half of those with smell loss. More research into treatment is needed, especially given that olfactory dysfunction is associated with depression and loss of appetite. Health professionals should be aware of these common and long lasting effects.

An objective approach for odor detection is to analyze the brain activity using imaging techniques during the odor stimulation. In this study, Functional Near Infrared Spectroscopy (fNIRS) is used to record hemodynamic response from the frontal region of the brain by using a 4-channel fNIRS system. The fNIRs data is collected during the odor detection task in which the subjects were asked to press a button when they detect the given odor. Functional Data Analysis (FDA) was applied on fNIRs data to convert discrete measured samples of data to continuous smooth curves. The FDA method enables us to use the bases coefficients of fNIRS smoothed curves for features that represent the shape of the raw fNIRS signal. With the learning algorithm that we proposed, these features were used to train the support vector machine classifier. We evaluated the odor detection problem, in two binary classification cases: odorant vs. non-odorant and odorant vs. fingertapping. The model achieved a classification accuracy of 94.12% and 97.06% over the stimulus condition in the two cases, respectively. Moreover to find the actual predictors we used the extracted defined features (slope, standard deviation, and delta) to train our classifier. We achieved an average accuracy of 91.18 % on classifying odorant vs. non-odorant and an accuracy of 94.12% for odorant vs. fingertapping on the stimulus condition. The results determined that fNIRs signals of odorant and non-odorant are distinguishable without being affected by the motor activity during the experiment.These findings suggest that fNIRs measurement on the forehead could be potentially used for objective and comparably inexpensive assessment of odor detection in cases that the subjective report is unreliable.

BACKGROUND: Considerable evidence suggests that smell dysfunction is common in coronavirus disease-2019 (COVID-19). Unfortunately, extant data on prevalence and reversibility over time are highly variable, coming mainly from self-report surveys prone to multiple biases. Thus, validated psychophysical olfactory testing is sorely needed to establish such parameters. METHODS: One hundred severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2)-positive patients were administered the 40-item University of Pennsylvania Smell Identification Test (UPSIT) in the hospital near the end of the acute phase of the disease. Eighty-two were retested 1 or 4 weeks later at home. The data were analyzed using analysis of variance and mixed-effect regression models. RESULTS: Initial UPSIT scores were indicative of severe microsmia, with 96% exhibiting measurable dysfunction; 18% were anosmic. The scores improved upon retest (initial test: mean, 21.97; 95% confidence interval [CI], 20.84-23.09; retest: mean, 31.13; 95% CI, 30.16-32.10; p < 0.0001); no patient remained anosmic. After 5 weeks from COVID-19 symptom onset, the test scores of 63% of the retested patients were normal. However, the mean UPSIT score at that time continued to remain below that of age- and sex-matched healthy controls (p < 0.001). Such scores were related to time since symptom onset, sex, and age. CONCLUSION: Smell loss was extremely common in the acute phase of a cohort of 100 COVID-19 patients when objectively measured. About one third of cases continued to exhibit dysfunction 6 to 8 weeks after symptom onset. These findings have direct implications for the use of olfactory testing in identifying SARS-CoV-2 carriers and for counseling such individuals with regard to their smell dysfunction and its reversibility.

BACKGROUND: Severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2), the virus that causes coronavirus disease 2019 (COVID-19), is responsible for the largest pandemic since the 1918 influenza A virus subtype H1N1 influenza outbreak. The symptoms presently recognized by the World Health Organization are cough, fever, tiredness, and difficulty breathing. Patient-reported smell and taste loss has been associated with COVID-19 infection, yet no empirical olfactory testing on a cohort of COVID-19 patients has been performed. METHODS: The University of Pennsylvania Smell Identification Test (UPSIT), a well-validated 40-odorant test, was administered to 60 confirmed COVID-19 inpatients and 60 age- and sex-matched controls to assess the magnitude and frequency of their olfactory dysfunction. A mixed effects analysis of variance determined whether meaningful differences in test scores existed between the 2 groups and if the test scores were differentially influenced by sex. RESULTS: Fifty-nine (98%) of the 60 patients exhibited some smell dysfunction (mean [95% CI] UPSIT score: 20.98 [19.47, 22.48]; controls: 34.10 [33.31, 34.88]; p < 0.0001). Thirty-five of the 60 patients (58%) were either anosmic (15/60; 25%) or severely microsmic (20/60; 33%); 16 exhibited moderate microsmia (16/60; 27%), 8 mild microsmia (8/60; 13%), and 1 normosmia (1/60; 2%). Deficits were evident for all 40 UPSIT odorants. No meaningful relationships between the test scores and sex, disease severity, or comorbidities were found. CONCLUSION: Quantitative smell testing demonstrates that decreased smell function, but not always anosmia, is a major marker for SARS-CoV-2 infection and suggests the possibility that smell testing may help, in some cases, to identify COVID-19 patients in need of early treatment or quarantine.

Objective assessment of olfactory function has diagnostic and legal value. We have designed an odor detection task in which the subject reported the conscious sensing of an odorant via a button press while the hemodynamic activity from the forehead was monitored using a 4-channel fNIRS system. The task consisted of intermingled odor and non-odor trials. We recorded from 17 subjects and each of them underwent 60 trials. The time domain analysis of the raw data showed that the hemodynamic activity was statistically different between the odor and non-odor trials especially for oxyhemoglobin in far channels. In order to single out the odor-induced hemodynamic response from that of motor activity, finger tapping was considered as a control condition for odor detection. Pairwise correlation indicated that motor activity had a short lasting influence on hemodynamic response while the hemodynamic response to different odors were highly correlated over time. In conclusion, we believe that fNIRS monitoring of hemodynamic response could be potentially used for objective assessment of odor detection in cases that subjective report is unreliable.