Long-term persistence of olfactory and gustatory disorders in COVID-19 patients.

To the Editor

High rates of taste and smell disorders were observed in patients with confirmed COVID-19 at the acute stage. In one meta-analysis of 15 studies involving 3739 patients, gustatory and olfactory disorder rates were estimated to be 49.1% and 61.3%, respectively [1]. In another meta-analysis of 24 studies with data from 8438 patients, the pooled proportions of those presenting with olfactory and gustatory dysfunction were 41.0% and 38.2%, respectively [2]. In our experience with 3737 COVID-19 patients, 39.2% reported anosmia and 37.8% ageusia [3]. Most studies addressing recovery rates were conducted during the first month after onset of symptoms. In one monocentre study with a 2-month follow-up conducted in 89 French patients with anosmia and or ageusia, 29 (32.6%) still reported these symptoms at day 60, based on questionnaire [4]. In another multicentre study conducted in 117 Italian patients with olfactory and/or gustatory disorders, 14 (12.0%) were still symptomatic at day 60, based on psychophysical tests [5]. In the present study we aimed to assess recovery rates at more than 6 months after onset of symptoms.

Patients who reported anosmia and/or ageusia at the acute phase of a COVID-19 PCR-confirmed episode were retrospectively identified from a cohort of 3737 patients seen at our institute between 3 March and 27 April 2020 [3]. Information about demographics, comorbidities and initial symptoms were retrieved from medical files. All patients were called by telephone between 1 and 3 November 2020 with the aim to evaluate recovery rates of olfactory and gustatory dysfunction using a questionnaire (please Supplementary material). Patients were asked whether or not they fully recovered their sense of smell or taste and to state the approximate duration of symptoms. Assuming a 50% loss in follow-up, a total of 200 patients were randomly selected to reach a convenience sample of 100 patients for this preliminary study. Data was pseudonymized and statistical analysis was conducted using R (R Core Team. R: A language and environment for statistical computing. R Foundation for Statistical Computing, Vienna, Austria, 2020. URL: https://www.Rproject.org/). The chi-squared or the Fisher exact test was used to compare differences between proportions when appropriate. Quantitative data means were compared using Student t-test.

Of 200 patients, 75 (37.5%) were lost in follow-up and 125 (62.5%) answered the questionnaire. Responding patients were relatively young with a low prevalence of comorbidities and presented with non-severe COVID-19 infection (Table S1). Their characteristics did not significantly differ from those of patients lost in follow-up (data not shown). Most patients presented with both taste and smell disorders. Mean time between symptom onset and follow-up questionnaire was about 7 months. Of the patients, 68.1% recovered their sense of smell and 73.0% their sense of taste during the first 6 weeks following the onset of symptoms (Fig. 1 ). Anosmia tended to take more time to resolve than ageusia. Of 125 patients with taste and smell disorders at the acute phase of COVID-19, 30 (24.0%) reported persistent taste and smell disorders 7 months after onset of symptoms. Of them, all reported anosmia at the acute phase and 26 an associated ageusia. Twenty-one of 30 (70.0%) reported partial recovery of olfaction sense and 7/30 (23.3%) no recovery at all, while 10/26 (38.5%) reported partial recovery of gustatory sense and 3/26 (11.5%) no recovery at all. Female patients were more likely to report persistent symptoms than male patients (73.3% versus 26.7%, respectively, p 0.02) (Table S2). Age, comorbidities, time between onset of symptoms and admission, severity of disease at admission and viral load did not significantly associated with persistence of symptoms.

Fig. 1

Number of patients with persistence of anosmia (red curve) and ageusia (blue curve) overtime.

Our study has several limitations including its small sample size and its interview-based design. In one study, about 10% patients self-reporting normal olfactory and gustative function were showed to have chemosensitive disorder on objective testing [5]. In addition, 37.5% of patients were lost in follow-up, and one possible reason is that they have recovered very well without any residual taste and smell problems. Nevertheless in this preliminary study, we identified a high 24% rate of persistence of olfactory or gustatory symptoms in COVID-19 patients more than 7 months after onset of symptoms with 23.3% and 11.5% of patients with persistent symptoms reporting complete anosmia or ageusia. Given the high prevalence of infection in the general population, COVID-19 will result in a large number of patients with long-term morbidity. Further studies based on validated discrimination tests including psychophysical tests or electrophysiological methods should be conducted to better characterize long-term olfactory and gustative disorder in COVID-19 patients. In addition, because hypometabolism of the olfactory/rectal gyrus was associated with persistence of anosmia and ageusia in a preliminary report, exploration of these patients with 18F-FDG brain positron emission tomography should be of great interest [5]. We did not find any predictive factors other than female sex for the persistence of symptoms, in line with results of another study [6].

Transparency declaration

Conflict of Interest Disclosures: None reported. Funding/Support: We had no dedicated support for the research.

Ethics approval

This study was approved by our institutional review board committee (Méditerranée Infection no. 2020-021) and conducted in the context of standard care.

Author contributions

Conceptualization: Philippe Gautret, Didier Raoult; Formal analysis: Van Thuan Hoang; Investigation: Nhu Ngoc Nguyen, Jean Christophe Lagier; Writing: original draft: Philippe Gautret; Writing: review and editing: Nhu Ngoc Nguyen, Van Thuan Hoang, Jean Christophe Lagier, Didier Raoult; Supervision: Philippe Gautret.