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Olfactory Dysfunction in COVID-19 Diagnosis and Management

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Olfactory Dysfunction in COVID-19 Diagnosis and Management Clinical Review & Education JAMA Insights | CLINICAL UPDATE Olfactory Dysfunction in COVID-19 Diagnosis and Management Katherine Lisa Whitcroft, BSc, MBChB; Thomas Hummel, MD As of May 1, 2020, more than 3 000 000 people worldwide have olfactory neuroepithelium may result in inflammatory changes been infected with the novel coronavirus, severe acute respiratory that impair olfactory receptor neuron function, cause subsequent syndrome coronavirus 2 (SARS-CoV-2). The CDC has highlighted key olfactory receptor neuron damage, and/or impair subsequent symptoms that may suggest coronavirus disease 2019 (COVID-19), neurogenesis. Such changes may cause temporary or longer- including cough, shortness of breath or difficulty breathing, fever, lasting OD. Previous work in transgenic animal models showed chills, muscle pain, sore throat, and new loss of smell or taste.1 intracranial entry of SARS-CoV via the olfactory bulb.8 This has led The inclusion of loss of smell or taste among these symptoms to speculation that SARS-CoV-2 may penetrate intracranially with follows the emergence of evidence that suggests that COVID-19 fre- possible downstream effects on olfactory and nonolfactory brain quently impairs the sense of smell. For example, in a study from Iran, regions, which may adversely affect olfactory function. 59 of 60 patients hospitalized with COVID-19 were found to have an impaired sense of smell according to psychophysical olfactory Clinical Assessment testing.2 Olfactory dysfunction (OD), defined as the reduced or dis- During the current pandemic, patients with recent-onset acute torted ability to smell during sniffing (orthonasal olfaction) or eat- smell and/or taste dysfunction, with or without other symptoms of ing (retronasal olfaction), is often reported in mild or even asymp- COVID-19, should undergo a period of self-isolation and, when pos- tomatic cases; in a study from Italy,64% of 202 mildly symptomatic sible, SARS-CoV-2 testing. In patients with symptoms that require patients reported impaired olfaction.3 acute hospital admission (eg, respiratory distress), chemosensory The possibility that OD could act as a marker for disease, par- assessment of smell and taste should only be considered when the ticularly among individuals who are otherwise minimally sympto- clinical condition allows and appropriate PPE is available. A possible matic or asymptomatic, prompted organizations, such as the approach to assessment is outlined in the Figure. American Academy of Otolaryngology–Head and Neck Surgery4 Subjective self-assessment of chemosensory function should and ENT UK,5 to recommend inclusion of sudden-onset loss of not be relied on for diagnosis because of limited correlation with smell and/or taste as part of the diagnostic criteria for COVID-19 dis- more objective measures.9 However, remote use of validated tools ease, as has now been done by the CDC. These organizations sug- (eg, visual analog scales, ordinal scales, patient-reported outcome gest that new-onset OD is sufficient to justify self-isolation and the measures) could allow safe, timely capture of data from self- use of personal protective equipment (PPE) by medical staff evalu- isolating patients. Although such findings should be interpreted ating patients with this clinical problem. with caution, this approach is acceptable in some patients with COVID-19 for whom psychophysical testing is not possible. Olfactory Dysfunction in COVID-19 Psychophysical assessment involves presentation of odorants/ Reports of COVID-19–related OD describe a sudden onset of tastants, with test outcome dependent on the patient’s response. olfactory impairment, which may be in the presence or absence Such tests are more reliable than a subjective assessment alone and of other symptoms. Among hospitalized patients with COVID-19 should be performed in patients with COVID-19 when possible. in Italy, impaired smell/taste was more frequently seen in younger Olfactory psychophysical assessment tools most commonly patients and in women.6 Unpublished data and anecdotal reports test 1 or a combination of odor threshold (minimum strength of an support resolution of olfactory symptoms within approximately odor that can be perceived), odor discrimination (differentiation 2 weeks. However, because of the lack of long-term follow-up, it between different odors), and odor identification (identification of is unknown what proportion of patients develop persistent odors). Ideally, tools targeting odor threshold, discrimination, and postinfectious OD. identification using a standard multicomponent olfactory testing Many patients report impairment of smell and taste inter- device should be employed. However, when fast assessment or changeably. Although it is possible that SARS-CoV-2 targets both self-administration is necessary, such as in the assessment of olfactory and gustatory systems, in most cases of dysfunction not patients with COVID-19, commercially available tools with fewer related to COVID-19 in which patients describe altered taste, this testing components, self-administered devices, or both may be symptom can be attributed to impaired retronasal olfaction considered.9 Any psychophysical test used clinically should be (flavor) rather than impaired gustation (sweet, salty, sour, bitter). validated for the population being tested, with the diagnoses of For this reason, it is thought that the chemosensory impairment impairment and improvement made in relation to age-matched, in COVID-19 is likely olfactory. clinically anchored normative data. Coronaviruses are one of many pathogens known to cause Because the majority of patients who report altered taste are postinfectious OD, and nasal epithelial cells show relatively high likely experiencing impaired retronasal olfaction, screening of expression of the angiotensin-converting enzyme 2 receptor, gustatory function should be sufficient as a first-line assessment. which is required for SARS-CoV-2 entry.7 Disruption of cells in the For patients in whom abnormalities are identified on screening, 2512 JAMA June 23/30, 2020 Volume 323, Number 24 (Reprinted) © 2020 American Medical Association. All rights reserved. Downloaded From: https://jamanetwork.com/ by rosana villanassi on 07/14/2020 JAMA Insights Clinical Review & Education Figure. Possible Approach for the Assessment and Management of Suspected Coronavirus Disease 2019 (COVID-19)–Related Olfactory Dysfunction Patient presentation with sudden onset of loss of smell or taste COVID-19 symptoms that require acute medical care COVID-19 symptoms that do not require acute medical care or no additional COVID-19 symptoms Acute hospitalization Self-isolation (duration per local guidelines) Test and treat for COVID-19 per local guidelines Test for COVID-19 per local guidelines Consider acute olfactory and gustatory assessment when Perform remote self-assessment of olfactory function if possible, including clinically appropriate, including subjective and psychophysical - Subjective assessment delivered via online questionnaires (see Chemosensory testing below) assessment (see Chemosensory testing below) - Psychophysical assessment using self-administered tools delivered to patient Do not perform nasendoscopy acutely given (see Chemosensory testing below); when this is not logistically possible, psychophysical aerosolization risk testing may be omitted, but results from subjective assessment alone should be viewed Wear personal protective equipment during any patient contact with caution Recovery from acute COVID-19 infection and completion of isolation period Residual chemosensory dysfunction No residual chemosensory dysfunction No further testing required Full assessment of COVID-19 OD Patient history Define impairment Define severity Orthonasal olfaction Reduced or absent external smells when sniffing Hyposmia Reduced smell Retronasal olfaction Reduced or absent flavor perception when eating Anosmia Absent smell Gustation Reduced or absent taste (sweet, salty, sour, bitter, umami) Hyperosmia Increased smell Parosmia Alteration in quality of smells Hypogeusia Reduced taste Parageusia Alteration in quality of taste Ageusia Absent taste Phantosmia Presence of smell in absence of stimulus Common differential diagnoses COVID-19 OD Sinonasal OD Posttraumatic OD Neurodegenerative OD - Sudden onset - Gradual onset - Sudden onset - Gradual onset - +/- COVID-19 symptoms - Nasal congestion, discharge, - Severe (anosmia) - Patients often unaware of smell or taste impairment - May be temporary or facial pain - +/- Parosmia or phantosmia - No fluctuation in severity - Patients may be younger and/or female - Fluctuation in severity - No fluctuation in severity - Patients may be older - Seasonal component - Memory or neurologic features Patient examination Perform full otolaryngologic examination including 3-pass rigid nasoendoscopy for patency or abnormalities of olfactory cleft and other sinonasal abnormalities, including features of malignancy or inflammatory disease (eg, polyps) Perform full neurologic examination when neurodegenerative or intracranial cause suspected Chemosensory testing Subjective assessment Psychophysical assessment Appropriate for remote use in self-isolation, but limited correlation with objective measures; Use validated, reliable tests if possible, do not use as only assessment Olfactory tests most commonly target one or a combination Options include visual analog scale, ordinal scale, or patient-reported of odor threshold (T), discrimination (D), and identification (I) outcome measures
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