Discussion
Over the last weeks, an increasing number of Authors reported a high rate of olfactory and gustatory dysfunctions in COVID-19 patients, sometimes presenting as the first symptom.4-14
The main goal of the present study was to evaluate the prevalence of smell/taste disorders in a large COVID-19 positive population, composed of patients who were either asymptomatic or presenting mild or moderate symptoms.
Our findings (66 and 65.4 % respectively, without gender differences) are similar to those of Yan et al. about a smaller sample of 59 positive patients;10 a recent European multicenter study reported higher percentages both for smell and taste disorders, with a female prevalence12.
Since only one study by Mao et al. referred to the prevalence of chemosensory impairment in Asiatic COVID-19 population (5%)9, our data seem to corroborate the hypothesis by Lechien et al. that western positive patients (USA and Europe) may be more subject to the development of olfactory and gustatory disorders12.
The majority of patients in this study complained of complete anosmia/ageusia, confirming the observation that COVID-19 related impairment tends to induce a severe olfactory and gustatory dysfunction.10,12
Of particular interest is the analysis of the timing of anosmia: the loss of smell was noted in 54% prior to diagnosis and appeared as the first symptom in 13% of cases. Recent onset of olfactory disorders may drive the physicians to treat these patients as possible COVID-19 positive: adequate precautions for the healthcare practitioners, PCR-testing and home self-isolation are crucial measures to avoid that such patients continuing to accidentally act as vectors of the disease.
Another pivotal issue of the research regards the recovery of olfactory and gustatory functions: 49.5% of patients reported a full regaining of both senses after 14 days since the beginning of the symptoms and this percentage improved to 62.9% at time of interview (23 days median, range 15-31), with a median recovery time of 10 days. Obviously, even if our follow- up is longer than other reports,10-12 it remains too short to give a conclusive interpretation regarding the prognosis.
Although the exact mechanism with which SARS-CoV-2 could impair smell and taste has not been definitively determined, two hypotheses appear to be plausible: damage to the olfactory epithelium, due to cell expression of angiotensin converting enzyme 2 (ACE2) receptors which act as a binding point for the virus16, or a direct assault on the olfactory neurons17. The relatively rapid and spontaneous recovery of most patients in the current and in other studies, tends to suggest an epithelial based pathogenesis, given the capability for the epithelium to quickly restore its functions after damage.10-12
According to some Authors, the presence of 15 variants of the ACE2 gene explains many ACE2 polymorphisms and differences in expression between European and Asian populations; this finding could be a cue to investigate if different patterns may influence susceptibility and clinical features of COVID-19 infection.18
The current study presents some limitations, shared by all similar researches. First of all, the patients did not undergo nasal endoscopy, specific imaging or objective smell assessment; these examinations would contribute to a better understanding of pathogenetic mechanisms and to define some prognostic factors about the functional recovery.
Second, the evaluation tool was a self-reported smell and taste score: It has been previously demonstrated that subjective evaluation of sense of smell is quite specific but less sensitive than objective testing.19 Moreover, the survey was rapidly developed by the Authors with the aim of collecting and sharing the most possible data in the shortest time; after such emergency contingency, additional validation is needed.
Third, even if our population is quite numerous, the sampling time was short and limited to a single center; future studies on larger samples can help to clarify the prevalence of anosmia/ageusia in COVID-19 patients.
Lastly, no patients in this study received specific treatment for olfactory or gustatory loss; currently no medical treatment has proved to be highly effective in post-viral anosmia.20-22 The potential risks of immunosuppression with the use of oral and some topical steroids also need to be borne in mind, consequently we agree with most authors, who recommend against specific therapy.4-8,12,13
A different approach could be applied to those patients with persistent olfactory disorders after complete recovery from COVID-19 and an exhaustive smell/taste assessment; in any case, further studies are needed in order to investigate potential benefits of treatment in selected cases.
Beyond the limitation, this is one of the first studies to provide the prevalence, the onset time, the severity and the recovery time of COVID-19 related smell and taste disorders; the follow-up time is acceptable and the sample is various and quite representative: Novara, indeed, is a small city (100000 inhabitants) near the border with the Lombardy Region, the epicenter of the Italian COVID-19 outbreak; at accrual time – March, the 30th-  the positive patients in the town were almost 800, of which 355 were enrolled in the current research.
The current study strongly confirms the high prevalence of olfactory and gustatory disorders in COVID-19 infection.22,23 Smell and taste loss may be used as indicators of potential contagion, and early identification may help to reduce the risk of spread, especially by paucisymptomatic cases.
REFERENCES
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FIGURE LEGENDS
Figure1
Smell (A) and taste (B) perception (score) before developing symptoms (baseline), at the highest intensity of symptoms (worst) and after two weeks from their onset (14 days).
Figure2
Daily rate of recovery for both smell (blue) and taste disorders (red).
Table 1 Characteristics of patients with SARS-CoV-2 infection included in the study