Long-term recovery from COVID-19 anosmia: Promising findings and unanswered questions.

Dear Editor,

We have read with great interest the follow‐up analysis by Lechien and coworkers on the long‐term persistence of COVID‐19‐associated anosmia [1]. The authors presented th0e results of a multicenter study that has followed a large cohort of hospitalized or home‐based COVID‐19 patients in order to assess the recovery time and patterns from olfactory or gustatory disturbances (OD/GD). The vast majority of patients, with both subjectively reported and objectively measured OD/GD, experienced a mild clinical form of the infection, thus consolidating the idea that upper airways are not only the main entry site for the novel coronavirus but also they may represent an important playmaker in the regulation of the subsequent systemic inflammatory response [2]. Most reassuringly, over 90% of them reported a complete recovery after 6 months and only the baseline severity of OD/GD emerged as a predictor of recovery. Nevertheless, the clinical management of the small proportion of patients who do not recover remains puzzling. In particular, we have now strong basic evidence that OD/GD is related to the immune‐mediated damage to the supporting (sustentacular and basal) cells in the nasal olfactory mucosa [3]. The disruption of the cellular architecture of the olfactory cleft leads to a functional obstruction of neural signal: though this ‘block’ appears to be mostly reversible, the subjects with persistent OD/GD show radiological evidence of damages to both the olfactory mucosa and olfactory nerve that probably result from a defective repair process [4]. Olfactory training and corticosteroids are the only two evidence‐based treatments against non‐COVID‐19‐related OD/GD but, in the absence of any published trials on the subject, their role in this pandemic deserves more attention [5]. First, following a structured identification of cases, odorant training should be proposed to all subjects who experience OD/GD and such a treatment should probably be started in the very early phases of the infection, in order to favour a constant stimulation of the residual olfactory function [6]. Secondly, the role of the administration of both systemic and intranasal steroids on the recovery pattern of COVID‐19 OD/GD has not been studied. In face of an initial fear for a negative impact on viral shedding and the risk of infection, there is now mounting evidence that these drugs are beneficial, at both high and low doses, in terms of COVID‐19‐related mortality [7]. It is biologically reasonable to conceive that this benefit might also affect the regain of the chemosensory function. Again, the timing seems crucial as the early administration of this class of drugs remains, at the moment, the only pharmacological way in order to try to counteract the aberrant inflammatory local mucosal response. As the world faces the threat of a third pandemic wave, these lessons should be kept in mind by all the physicians involved in this fight.

Conflict of interest

All authors declare they have nothing to disclose.

Luca Giovanni Locatello: Conceptualization (equal); Writing‐original draft (equal). oreste gallo: Writing‐review & editing (equal).