The recovery of smell sense is a challenging issue in patients with OD related to COVID-19. In this study, patients who adhered to an OT protocol reported better 6–12-month evolution of Sniffin’Sticks tests than those who did not adhere to OT. Indeed, after 6 months, the olfaction evolution results of the non-OT group have been flat, which may support the usefulness of OT protocol in the olfactory recovery process. The findings of the present study are consistent with previous studies supporting the effectiveness of OT in patients with post-viral loss of olfactory sense [9, 16, 17]. In a systematic review, Yuan et al. reported that olfactory function of patients with post-viral loss of smell sense was significantly improved through the use of nasal corticosteroids or the adherence to an standardized or modified OT [17]. In 2018, Oleszkiewcz et al. observed that among patients with several causes of OD, the OT was more effective in post-infectious OD [16]. Our study is an additional investigation supporting the effectiveness of OT in post-viral loss of smell sense, with the particularity that the OD was related to SARS-CoV-2. Indeed, to the best of our knowledge, there is no similar study investigating the effectiveness of OT on hyposmic or anosmic COVID-19 individuals. Only Altundag et al. reported the effectiveness of a modified OT protocol on COVID-19 patients with parosmia but this profile of patients differed from ours (hyposmia–anosmia patients). From a pathophysiological standpoint, the repeated short-term exposure to odors may increase both the growth of olfactory receptor neurons and the expression of olfactory receptor in the olfactory cleft mucosa [9, 19]. The positive influence of OT may also involve olfactory bulb and brain changes [9, 20]. Thus, Gellrich et al. recently reported that the adherence to an OT was associated with an increase of gray matter volume of the hippocampus and the thalamus, which are both involved in the memory of olfactory stimuli [20].

In practice, we commonly meet OD patients with aroma disorders (retro-olfaction) and related eating disorders; most of them with parosmia [21]. This problem was highlighted in the present study with 75.4% and 78.9% of patients reporting a significant impact of OD on their daily life and social activity, respectively. Because the adherence to an OT was proposed to enhance the sensitivity of foods and beverages [9], the proposition of such protocol or a modified parosmia-protocol [18] makes particularly sense in these patients.

In this study, 35.1%, 26.3% and 43.9% of patients reported cacosmia, phantosmia or parosmia throughout the follow-up period, which corroborates the literature findings. The post-COVID-19 prevalence of phantosmia ranged from 20.5 to 48%, while 18–73% reported parosmia within the post-COVID-19 months [22,23,24,25]. Interestingly, we observed a higher proposition of phantosmia in the OT group compared to the control group. We did not find similar findings in the literature.

The low number of patients is the main limitation of the present study. The low number of patients was related to the exclusion of many patients who did not report details about the adherence of OT protocol or who missed an evaluation consultation. The lack of use of the threshold, discrimination and identification test (TDI, 48 pens) is another limitation, because TDI provides additional information about smell sense through the threshold and discrimination parts. Our team did not use TDI, because at the onset of the pandemic, it was difficult to perform any long testing evaluations regarding the patient consultation restrictions in the medical centers of our country. These restrictions limited us in the realization of complete psychophysical evaluations, nasofibroscopy and imaging in COVID-19 patients included during the first European wave. The design of the study is another limitation. Precisely, the OT recommendation in all included patients (non-OT and OT groups) may be associated with a bias. Furthermore, since the No-OT group was recommended OT, one cannot assume that this group had so little exposure to the intervention.

The prospective design with several timepoints of olfactory evaluations (6, 12, and 18 months) is the main strength of the study. The evaluations of the patient adherence to the OT throughout the follow-up is an additional strength of the study. Indeed, to the best of our knowledge, there were no similar studies assessing the effectiveness of OT throughout the 18-month post-infection.