key: cord-0952773-843he4ta
authors: Cirillo, Nicola; Colella, Giuseppe
title: Self-reported smell and taste alteration as the sole clinical manifestation of SARS-CoV-2 infection
date: 2020-12-08
journal: Oral Surg Oral Med Oral Pathol Oral Radiol
DOI: 10.1016/j.oooo.2020.11.016
sha: 81266dc29a2a8126f0a35f17b76eff8ab41da323
doc_id: 952773
cord_uid: 843he4ta

Chemosensory disfunctions have been increasingly reported in patient with coronavirus disease 2019 (COVID-19). Here, we document a case of a patient with taste and smell alterations as the only clinical manifestations of SARS-CoV-2 infection. In March 2020, a 36-year old female presented with self-reported hypo/ageusia and hypo/anosmia in the absence of any respiratory symptom. The patient, who had no clinical and radiographic signs of sinusitis and was otherwise healthy, eventually tested positive for SARS-CoV-2. She did not develop any COVID-19-related symptom throughout the 6-month follow up. Her self-reported chemosensory discfunction lasted for 12 weeks. To the best of our knowledge, this was the first report that accurately documented taste and smell alteration as the sole manifestation of COVID-19 in an otherwise healthy individual. Overall, analysis of current evidence supports the inclusion of gustatory and olfactory alterations as cardinal symptoms of COVID-19. Dentists’ awareness of the diagnostic criteria for case definition of COVID-19 can facilitate an early detection of the disease.

Early detection of individuals infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is key to reduce the spread of coronavirus disease 2019 and is particularly challenging in asymptomatic or paucisymptomatic patients. Commonly reported clinical manifestations of COVID-19 include fever, cough, myalgia or fatigue, pneumonia, and complicated dyspnea 1 . Whilst the most prevalent signs/symptoms in COVID-19 patients (i.e. cough, fever, and fatigue, according to a recent meta-analysis 2 ) have been used as cardinal clinical diagnostic criteria since the beginning of the outbreak, new olfactory and taste disorder(s) were not initially linked to SARS-CoV-2 infection and have not been used for case identification and testing prioritization by the US Centers for Disease Control and Prevention (CDC) or World Health Organization (WHO) until August 2020. 3 The first systematic assessments of the evidence available up to March 2020 failed to identify associations between anosmia/ageusia and COVID-19 4, 5 . For example, none of the studies included in an early systematic review reported about olfactory or gustative dysfunctions 4 . When looking specifically at the evidence for anosmia in COVID-19 up to 23 March, researchers found it to be "limited and inconclusive" 5 . In sharp contrast, the most recent meta-analysis analyzing smell and taste alterations not only reported that approximately half of COVID-19 patients had these symptoms but, also, that 15% of patients had olfactory and gustatory abnormalities as their initial clinical manifestations 6 .

In agreement with the growing body of evidence, sudden onset of anosmia, ageusia or dysgeusia have now been recognized as major clinical characteristics of the disease and have been included Here, we aimed to document a case of a patient with taste and smell alterations as the only clinical manifestations of SARS-CoV-2 infection. Furthermore, we surveyed current high-level evidence on this topic. She was followed up by telephone surveys and, in the following weeks, did not report any respiratory or other symptoms except anosmia and ageusia. These self-reported alterations began to gradually improve in May and resolved by 25 th May. No VAS testing was possible due to the telephone interviews. As at 29 th August 2020, no new self-reported alterations of taste and smell were reported. After providing thorough information regarding the publication of this case, informed consent was gathered.

To the best of our knowledge, this is the first report of a case of COVID-19 with no comorbidities, no medication history and without any symptoms except concomitant loss of smell and taste. A previous study described a patient with anosmia and ageusia as the only indicators of COVID-19 8 , however this patient presented to hospital with the chief complaint of headache, which is now a well-known neurological manifestation of COVID-19 9-12 . Furthermore, this 60-year-old woman had a history of vertigo, seasonal allergies and trigeminal neuralgia. In contrast, our patient had no systemic diseases or allergies. In another report from Norway, a married couple in their sixties reported anosmia (wife) and ageusia (husband), however there was no concurrent alteration of smell and taste 13 . Finally, another peculiarity of our case was the unusually long duration of the symptoms, which lasted for approximately 12 weeks.

We found retrospective studies where patients who tested positive for SARS-CoV-2 appear to have suffered from chemosensory dysfunctions in the absence of typical COVID-19 symptomatology 14, 15 . For example, Villareal et al 14 Given the potential usefulness of smell and taste assessment in the diagnosis on asymptomatic patients, we undertook a review of high-level evidence on this topic. The data extracted from published systematic reviews are reported in Table 1 . The range of prevalence of olfactory and gustatory alterations, when reported individually, was 3.2-100% and 0-92.6%, respectively. In the systematic reviews analyzing smell and/or taste together, the range was 5.6-94%. The heterogeneity of these findings may be partially due to differences in the geographical distribution of this association 3 . Interestingly, when the prevalence was pooled on the total number of cases examined, olfactory and gustatory alterations were found in approximately half of COVID-19 patients. In one systematic review 29 , 81.6% (8,823) and 74.8% (8,088) out of 10,818 COVID-19 patients presented with ageusia and anosmia, respectively. Studies 6 also demonstrate that the same signs/symptoms are the initial manifestation in a sizeable number of patients. In light of the data reported here, it is imperative for dentists and oral healthcare providers to recognize ageusia as a potential clinical manifestation of COVID-19.

Smell and taste disorders are not rare in the general population and recognize a wide range of causes, including cigarette smoking, nasal and sinus disease, oral or upper respiratory infection, head trauma, neurodegenerative disorders, brain neoplasms, and aging 33 . Medications, chemotherapy and radiotherapy are also associated with chemosensory disfunctions 34 . It is not surprising, therefore, that changes of smell and/or taste were also found to be relatively common in SARS-CoV-2-negative patients 35 . In the case presented here, we ruled out smoking, trauma, medications, infections, and sinus disease based on the information gathered from medical history, clinical assessment and radiographic investigations. The patient could not undertake the neurological assessment prescribed by us due to self-isolation, but given the transitory nature of her alteration and considering the positivity to SARS-CoV-2 testing, it is unlikely that her disturbances were related to brain disease.

The possible mechanisms of chemosensory disfunction in COVID-19 are still being elucidated.

The high incidence of smell loss without significant rhinorrhea or nasal congestion suggests that SARS-CoV-2 targets the chemical senses through mechanisms distinct from those used by endemic coronaviruses or other common cold-causing agents 36 . It has been proposed that the virus could bind to the olfactory and/or oral epithelium via ACE2 receptor and induce cytolytic damage and inflammatory responses. In turn, this would lead to cellular and genetic changes that could ultimately alter taste and smell 37 . The same mechanism could also directly affect the peripheral neuronal trajectory of the gustatory tract. Another study suggests that the rapid recovery of smell and taste functions in COVID-19 patients could be attributed to a decrease in interleukin-6 levels 38 . While intriguing, these reports are still very speculative and will need to be backed by further experimental and clinical evidence.

Smell and taste alterations are not only associated with COVID-19 but can be the first or sole manifestations of the disease. As at 29 August 2020, our patient had not developed any COVIDrelated or other signs or symptoms. Hence, to the best of our knowledge, this is the first COVID-19 patient presenting with prolonged ageusia and anosmia as the sole clinical manifestations of the disease during a 6-month follow-up. 

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Systematic reviews were sorted by date of publication on PubMed. S, smell; T, taste; ST, smell and taste; N, neurological; G, general symptoms; NR

*, exact date not specified, assumed 30 April. **, date(s) of data collection not specified