key: cord-0754890-tq66r91z
authors: Gurrola, José G.; Chang, Jolie L.; Roland, Lauren T.; Loftus, Patricia A.; Cheung, Steven W.
title: Short‐term chemosensory distortions and phantoms in COVID‐19
date: 2021-02-01
journal: Laryngoscope Investig Otolaryngol
DOI: 10.1002/lio2.532
sha: 4a14762383401ad8e8c89de22ff2f1b74e477a05
doc_id: 754890
cord_uid: tq66r91z

OBJECTIVE: To identify differentiation features of chemosensory dysfunction in COVID‐19 infection and their primary drivers. STUDY DESIGN: Cross‐sectional cohort comparison. METHODS: A national anonymous survey was used to query participants regarding nasal symptoms and chemosensory dysfunction including sensitivity levels, and presence or absence of distortions and phantoms within the 6‐week time window surrounding their COVID‐19 testing and survey completion. RESULTS: Three‐hundred and sixty‐four respondents who reported COVID‐19 positive (COVID+; n = 176) or COVID‐19 negative (COVID−; n = 188) test results completed the survey. The COVID+ cohort had higher occurrence rates for: (a) chemosensory sensitivity impairments (67.0% vs 30.3%; P < .01), where the rate of complete loss of smell (anosmia) or taste (ageusia) was higher (35.8% vs 4.8%; P < .01), and (b) chemosensory distortions (39.8% vs 19.1%; P < .01), where the rate of anosmia or ageusia with distortions was also higher in the COVID+ cohort (19.9% vs 2.7%; P < .01). Occurrence rates in the two cohorts were similar for chemosensory phantoms (COVID+ 17.0%, COVID− 18.6%; P = .70) and nasal discharge or stuffiness in the presence of sensitivity impairment (COVID+ 63.6%, COVID− 52.6%; P = .17). CONCLUSION: Chemosensory dysfunction in COVID‐19 is associated with higher rates of smell or taste sensitivity impairments and distortions. Higher rates of anosmia and ageusia drive these key findings. Chemosensory phantoms and nasal symptoms in the presence of sensitivity impairment occur at rates that should demand clinical attention, but they do not appear to be specific to COVID‐19 positivity. LEVEL OF EVIDENCE: 2b.

The chemosensory consequences of complete (anosmia) [1] [2] [3] [4] [5] and incomplete (hyposmia) [6] [7] [8] smell sensitivity impairment have been recognized as early symptoms of COVID-19 infection. Although several early studies suggested rapid subjective recovery, more recent studies showed some patients have persistent dysfunction beyond 2 weeks from their COVID-19 test by self-report or objective assessment. 3, 7, 8 As the COVID-19 pandemic has spread worldwide, rates of chemosensory dysfunction ranging from 5.1% to over 85% have been reported. [1] [2] [3] [8] [9] [10] [11] [12] Not unsurprisingly, taste sensitivity impairment is reported at similar rates of occurrence relative to smell loss. 4, 7, 8, 12 While smell and taste distortions and phantoms are part and parcel of chemosensory dysfunction triggered by insult of any form, much less is known about them, especially in relation to COVID-19 infection.

Lechien et al 3 reported rates of 79.6% and 78.9% for anosmia and ageusia, respectively, and 32.4% for parosmia and 12.6% for phantosmia in COVID-19 test positive patients. Chary et al 7 reported rates on the order of 5% for each separate category of parosmia, phantosmia, parageusia, and phantogeusia. Separate from viral-mediated causes, chemosensory dysfunction increases with age, where the rate of parosmia is 20.3% for smoke-related odors and 31.3% for natural gas odors in septuagenarians and older adults. 13 Within a specialty olfactory disorders clinic, Landis et al reported a rate of 15% for phantosmia. 14 Viral infection mediated chemosensory dysfunction is common in patients who present to smell and taste clinics for evaluation. [15] [16] [17] [18] [19] Increased nasal airway resistance and nasal secretions are often associated with viral upper respiratory infections and may contribute to chemosensory dysfunction. 20 Volunteers inoculated with a non-COVID-19 human coronavirus demonstrated increased nasal congestion and decreased smell sensitivity. 21 The presence of viral pathogens in nasal discharge suggests that chemosensory dysfunction may take place through direct injury to the olfactory system, both in isolation without and in conjunction with nasal obstruction-related conductive loss. 22 The COVID-19 pandemic presents a rare opportunity to define interrelationships among the chemosensory dysfunction categories of sensitivity levels, distortions, and phantoms. There is strong interest among COVID-19 test positive (COVID+) and test negative (COVID−) patients to engage in research that would inform clinical counseling and investigative direction. We performed a cross-sectional qualitative study to compare COVID+ and COVID− cohorts across all three chemosensory dysfunction categories using an integrated survey to examine occurrence rate differences and identify drivers of those differences within the 6-week time window surrounding their COVID-19 testing and survey completion. The mean (SD) age in years was 38.4 (13.1) in the COVID+ and 37.7 (10.6) in the COVID− cohorts (P = .27). Female participants were the majority in both cohorts, but the rates differed (P = .02). Ninety-seven percent (n = 353) of respondents did not require hospital admission.

The survey queried COVID-19 test results, demographic information, level of smell sensitivity (anosmia, hyposmia, normosmia), level of taste sensitivity (ageusia, hypogeusia, normogeusia,), presence or absence of smell and taste distortions, presence or absence of smell and taste phantoms, and presence of nasal symptoms of runny (rhinorrhea) or stuffy nose. Study participants were asked to report symptoms for the 2 weeks leading up to their COVID-19 test and the 2 days prior to survey completion. The median time interval between COVID-19 testing and survey completion was 11 days (95% confidence interval = 1-31 days). From those two time points, we integrated response data to extract nadir values for reporting occurrence rates of chemosensory (smell or taste) distortions and phantoms within the initial 6 weeks of viral infection. The conservative 6-week time estimate was derived by adding time windows of 2 weeks prior to COVID-19 testing and 4 weeks up to survey completion within the confidence interval of response dates. The higher rate of occurrence for either smell or taste was chosen in order to represent the most severe chemosensory dysfunction experienced for each respondent.

Subcategory features of smell and taste sensitivity impairments, distortions, and phantoms were combined into a single descriptor to capture discrete and interactive effects of chemosensory dysfunction. It is well known that smell dysfunction impacts taste, where several recently published COVID-19 related studies have reported a correlation between olfactory and gustatory abnormalities, [2] [3] [4] 6 

Chemosensory sensitivity impairments occurred more frequently in the COVID+ cohort compared to the COVID− cohort (67.0% vs 30.3%; P < .01; Table 1 ). In subcategory dichotomous contingency analysis, the rate of complete loss of smell (anosmia) or taste (ageusia) was higher in the COVID+ cohort (35.8% vs 4.8%; P < .01). In contrast, the rates of reduced smell sensitivity (hyposmia) or taste sensitivity (hypogeusia) were similar (31.2% vs 25.5%; P = .23).

Chemosensory distortions also occurred at higher rates in the COVID+ cohort (Table 1 ). The rate of parosmia or parageusia was higher in the COVID+ cohort (39.8% vs 19.1%; P < .01). In subcategory univariate analysis, the rate of complete loss of smell or taste was similarly higher in the COVID+ cohort (19.9% vs 2.7%; P < .01).

For distortions and hyposmia or hypogeusia, the rates were similar Nasal symptoms (rhinorrhea only, stuffy nose only, and combined rhinorrhea and stuffy nose) in the presence of chemosensory sensitivity impairments occurred at similar rates in the two cohorts. While no significant difference in overall nasal congestions was found, recent studies suggest COVID-19 specifically impacts the peripheral olfactory system, where expression of ACE2 and TMPRSS2 genes are found in the olfactory epithelium, but not in olfactory neurons. 26, 27 Molecular assays on olfactory epithelium and neuronal tissues in conjunction with clinical assessments of nasal symptoms will be required to assess the pathophysiology and relationships between nasal congestion vs chemosensory dysfunction in COVID-19.

Complete (anosmia or ageusia) and incomplete (hyposmia or hypogeusia) chemosensory sensitivity loss were the two features significantly associated with COVID-19 positivity on logistic regression.

This finding is internally consistent with chemosensory distortions arising from sensitivity impairments, and suggests that chemosensory phantoms and sensitivity dependence on nasal symptoms is not associated with COVID-19 positivity.

There are several limitations to this study that relate to anonymous national survey data capture. During the early days of COVID-19 and stringent shelter in place orders, in-person access to COVID-19 positive and negative study participants was limited. The cohort evaluated represented relatively healthy outpatients with internet and social media access, which limits the generalizability of results across all segments of the COVID-19 positive population. Recall and respondent biases, undisclosed relevant comorbidities, and possible duplicate entries inherent to this study design may introduce noise to our data.

Self-assessment of olfactory function can be inaccurate 28 and qualitative ratings of chemosensory sensitivity without quantitative threshold testing is suboptimal, although for this study, the ability to directly assess COVID-19 suspected patients with objective olfactory and gustatory assessment was inadvisable and unactionable. Stated presence of chemosensory distortions and phantoms without quality and severity characterizations is incomplete, although this remains an inherent limitation given the lack of objective tests to assess chemosensory distortions and phantoms. Measurement uncertainties surrounding chemosensory sensitivity ratings, distortions, and phantoms may introduce variance to prevalence estimates. Given the anonymous nature of the online survey, the potential exists for duplicate survey completions. Electively provided e-mail addresses to assess for duplicates show the rate to be <1%. Key findings from this cross-sectional study within a 6-week time window should be elaborated in greater detail and evaluated for persistence in a longitudinal study.

Chemosensory dysfunction in COVID-19 is differentiated by higher rates of smell or taste sensitivity impairments and distortions, mainly due to higher rates of anosmia and ageusia. Chemosensory phantoms and nasal symptoms occur in the presence of sensitivity impairment, but do not appear to be specific to COVID-19 positivity.

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