We previously observed that the prevalence of smell or taste dysfunction during the Omicron period dropped from 63–25% and from 57–27%, respectively, when compared with the frequency observed during the pre-Omicron phase of the pandemic [14]. Moreover, the severity of the smell and taste dysfunction was lower in subjects infected during the predominance of the Omicron variant [14]. In the present study, we also found a very favourable evolution with a prevalence of persistent dysfunction of 1.4% 6-month after SARS-CoV-2 infection acquired during the predominance of the Omicron BA.1 subvariant, reflecting a recovery rate of 96%. These figures are better than we observed 6-months after infection with G614 variant when the prevalence and the recovery rate were 18% and 70%, respectively [16].
While the onset of chemosensory changes did not appear to be affected by the vaccination status, the duration of symptoms was significantly shorter in the vaccinated subjects. These findings suggest that both a different biology of the variant and vaccination may be responsible for the different landscape of the alterations in smell and taste observed in subjects infected since Omicron BA.1 subvariant became predominant. The Omicron variant of SARS-CoV-2 carries over 30 mutations in its spike protein which inefficiently uses the cellular protease TMPRSS2 [17]. This both compromises cell entry in TMPRSS2-expressing cells and syncytia formation which was supposed to be a pathogenic mechanism for COVID-19 related smell dysfunction [18]. Another support to the theory of minor pathogenicity is given by the recent study by Armando et al. [11] in which hamsters were infected with D614G and Gamma, Delta and Omicron variants. At the histopathological analysis of samples taken from the olfactory mucosa, the animals infected with the latter variant showed significantly less severe and widespread alterations than the previous variants.
Secretory IgA (sIgA), located on the mucous membranes may play a crucial role in mucosal immunity [19]. Vaccines delivered through the parenteral intramuscular route elicit primarily circulating antibodies [20]. However, recent studies provided evidence that both systemic and nasal/salivary mucosal sIgA responses are induced after SARS-CoV-2 mRNA vaccination [21, 22] with mucosal humoral immune response being stronger after the injection of the second vaccine dose compared to subjects recovered from COVID-19 [22]. High levels of nasal IgA represent the only factor for which a positive correlation was found with the recovery of olfactory function after COVID-19 [23]. Such evidence provides mechanistic support to our observation of faster recovery of smell and taste dysfunction in vaccinated subjects.
Subjects with combined self-reported alterations in both sense of smell and taste had significantly longer recovery times regardless of vaccination status. A similar correlation between associated smell and taste loss during the infection and duration of olfactory dysfunction was found by Ferreli et al. [24] in a study conducted during the alpha variant period. It is well known that patients may self-report loss of taste when they develop loss of flavor perception as a consequence of an impairment in the retronasal olfactory function. Thus, some patients with isolated alteration of the sense of smell may have suffered less extensive damage to the olfactory neuroepithelium such as not to compromise the retronasal sense of smell and characterized by faster recovery times [25]. The isolated alteration of the sense of taste could depend in some cases on other factors such as drugs administered during the acute phase of the disease, so that these patients could have rapidly recovered from hypogeusia after drug discontinuation [26].
This study has the following limitations. First, symptoms were self-reported and based on telephone interview. These studies have several advantages: they were easy to be carried out, quick, and most importantly they have a baseline parameter of comparison that is, the subjective perception of smell preceding the onset of covid-19. However, it has been previously demonstrated that, compared with psychophysical evaluation, this approach is a source of important bias as it significantly underestimates the real prevalence and severity of the chemosensory dysfunction [18, 19]. Particularly, patients tend to overestimate the recovery from olfactory dysfunction. Thus, a psychophysical evaluation is warranted to identify patients with an unconscious alteration of the sense of smell that could expose them to environmental risks. Second, patients were included in the study based on epidemiological data from small samples sequenced regionally and we unable to estimate to what extent the sample was contaminated by non-Omicron cases. However, to reduce this bias, we decided to limit the analysis to cases of SARS-CoV-2 infection diagnosed when the Omicron variant was estimated to be above 95%.