Olfactory Loss of Function as a Possible Symptom of COVID-19—Reply

Abstract

In Reply We read with great interest the recent letters by Lechner et al, Malnic and Glezer, and Kheok and Yang in JAMA Otolaryngology-Head and Neck Surgery regarding our recent study. 1 There is now strong evidence that patients with proven severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection might develop loss of smell and taste, and in some cases this might constitute the main symptom.The nasal epithelium is divided into the respiratory epithelium and the olfactory epithelium.The olfactory clefts are at the upper part of the nasal cavities and constitute a crucial pathway for odorant molecules to the olfactory epithelium.We also agree with Malnic and Glezer that the most plausible explanation for the olfactory loss is the expression of the ACE2 receptor in the olfactory epithelium because SARS-CoV-2 infects cells through interactions between its S protein and the ACE2 protein on target cells. 1However, we should mention that, at the time of submission of our study, the ACE2 research was not yet available.Since then, we have raised the hypothesis that this inflammatory obstruction of the olfactory clefts might be the result of the interaction between SARS-CoV-2 and ACE2 protein expressed by the olfactory epithelium. 2 Lechner et al question the inflammatory obstruction of olfactory clefts observed on magnetic resonance imaging (MRI) as the cause of the olfactory function loss, since most patients did not appear to exhibit significant nasal congestion or runny nose.However, patients with isolated olfactory cleft obstruction, without nasal epithelium inflammation, do not usually report nasal obstruction. 3Moreover, we would like to underscore that the lack of these symptoms seems conceivable because only 10% of inhaled air actually reaches the olfactory clefts during normal resting breath. 4 Kheok and Yang claimed that this obstruction of the olfactory clefts is not the cause of olfactory function loss because another imaging case study did not report this anomaly. 5However, careful reassessment of the MRI images of this case report and detailed reflection of the anatomy demonstrate a bilateral obstruction of the olfactory clefts.Kheok and Yang noted that our scan images showed presence of a mild mucosal thickening in the paranasal sinuses, which might explain the opacification of the olfactory clefts.However, we would like to remind the authors that a mild asymmetrical thickening of the mucosa might be observed in asymptomatic patients, which is related to the nasal cycle.Moreover, Kheok and Yang provided the computed tomographic (CT) paranasal sinus images of a single patient with SARS-CoV-2 infection associated with anosmia, and without olfactory cleft obstruc-

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