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
1. Suzuki M, Saito K, Min WP, et al. Identification of viruses in
patients with postviral olfactory dysfunction. Laryngoscope.
2007;117(2):272–277. doi:10.1097/01.mlg.0000249922.37381.1e
2. Wu Z, McGoogan JM. Characteristics of and Important Lessons From the
Coronavirus Disease 2019 (COVID-19) Outbreak in China: Summary of a
Report of 72 314 Cases From the Chinese Center for Disease Control and
Prevention [published online ahead of print, 2020 Feb 24]. JAMA.
2020;10.1001/jama.2020.2648. doi:10.1001/jama.2020.2648
3. Huang C, Wang Y, Li X, et al. Clinical features of patients infected
with 2019 novel coronavirus in Wuhan, China [published correction
appears in Lancet. 2020 Jan 30;:]. Lancet.
2020;395(10223):497–506. doi:10.1016/S0140-6736(20)30183-5
4. Gautier JF, Ravussin Y. A New Symptom of COVID-19: Loss of Taste and
Smell [published online ahead of print, 2020 Apr 1]. Obesity (Silver
Spring). 2020;10.1002/oby.22809. doi:10.1002/oby.22809
5. Eliezer M, Hautefort C, Hamel AL, et al. Sudden and Complete
Olfactory Loss Function as a Possible Symptom of COVID-19 [published
online ahead of print, 2020 Apr 8]. JAMA Otolaryngol Head Neck Surg.
2020;10.1001/jamaoto.2020.0832. doi:10.1001/jamaoto.2020.0832
6. Gane SB, Kelly C, Hopkins C. Isolated sudden onset anosmia in
COVID-19 infection. A novel syndrome? [published online ahead of
print, 2020 Apr 2]. Rhinology. 2020;10.4193/Rhin20.114.
doi:10.4193/Rhin20.114
7. Vaira LA, Salzano G, Deiana G, De Riu G. Anosmia and ageusia: common
findings in COVID-19 patients [published online ahead of print, 2020
Apr 1]. Laryngoscope. 2020;10.1002/lary.28692. doi:10.1002/lary.28692
8. Giacomelli A, Pezzati L, Conti F, et al. Self-reported olfactory and
taste disorders in SARS-CoV-2 patients: a cross-sectional study
[published online ahead of print, 2020 Mar 26]. Clin Infect Dis.
2020;ciaa330. doi:10.1093/cid/ciaa330
9. Mao L, Jin H, Wang M, et al. Neurologic Manifestations of
Hospitalized Patients With Coronavirus Disease 2019 in Wuhan, China
[published online ahead of print, 2020 Apr 10]. JAMA Neurol.
2020;10.1001/jamaneurol.2020.1127. doi:10.1001/jamaneurol.2020.1127
10. Yan CH, Faraji F, Prajapati DP, Boone CE, DeConde AS. Association of
chemosensory dysfunction and Covid-19 in patients presenting with
influenza-like symptoms [published online ahead of print, 2020 Apr
12]. Int Forum Allergy Rhinol. 2020;10.1002/alr.22579.
doi:10.1002/alr.22579
11. Kaye R, Chang CWD, Kazahaya K, Brereton J and Denneny III JC.
COVID-19
Anosmia Reporting Tool: Initial Findings. 2020. Accepted for
publication by Otolaryngology–Head and Neck Surgery.
12. Lechien JR, Chiesa-Estomba CM, De Siati DR, et al. Olfactory and
gustatory dysfunctions as a clinical presentation of mild-to-moderate
forms of the coronavirus disease (COVID-19): a multicenter European
study [published online ahead of print, 2020 Apr 6]. Eur Arch
Otorhinolaryngol. 2020;10.1007/s00405-020-05965-1.
doi:10.1007/s00405-020-05965-1
13. Hopkins C, Surda P, Kumar N. Presentation of new onset anosmia
during the COVID-19 pandemic [published online ahead of print, 2020
Apr 11]. Rhinology. 2020;10.4193/Rhin20.116. doi:10.4193/Rhin20.116
14. Moein ST, Hashemian SMR, Mansourafshar B, Khorram-Tousi A, Tabarsi
P, Doty RL. Smell dysfunction: a biomarker for COVID-19 [published
online ahead of print, 2020 Apr 17]. Int Forum Allergy Rhinol.
2020;10.1002/alr.22587. doi:10.1002/alr.22587
15. Massachusetts General Hospital COVID-19 Treatment Guidance.
https://www.massgeneral.org/assets/MGH/pdf/news/coronavirus/covid19_domID_treatmentGuide.pdf
2020 (Accessed March 21, 2020)
16. Brann D, Tsukahara T, Weinreb C, Logan DW, Datta SR. Non-Neural
Expression of SARS-CoV-2 Entry Genes in the Olfactory Epithelium
Suggests Mechanisms Underlying Anosmia in COVID-19 Patients.
Neuroscience; 2020.
17. Baig AM, Khaleeq A, Ali U, Syeda H. Evidence of the COVID-19 Virus
Targeting the CNS: Tissue Distribution, Host–Virus Interaction, and
Proposed Neurotropic Mechanisms. ACS Chem Neurosci. 2020;11(7):995-998).
18. Cao Y, Li L, Feng Z, et al. Comparative genetic analysis of the
novel coronavirus (2019-nCoV/SARS-CoV-2) receptor ACE2 in different
populations. Cell Discov. 2020;6:11. Published 2020 Feb 24.
doi:10.1038/s41421-020-0147-1
19. Boesveldt S, Postma EM, Boak D, et al. Anosmia-A Clinical Review
[published correction appears in Chem Senses. 2017 Sep 1;42(7):607].Chem Senses. 2017;42(7):513–523. doi:10.1093/chemse/bjx025
20. Hummel T, Whitcroft KL, Andrews P, et al. Position paper on
olfactory dysfunction. Rhinol Suppl. 2017;54(26):1–30.
21. Harless L, Liang J. Pharmacologic treatment for postviral olfactory
dysfunction: a systematic review. Int Forum Allergy Rhinol.
2016;6(7):760–767. doi:10.1002/alr.21727
22. Soler ZM, Patel ZM, Turner JH, Holbrook EH. A primer on
viral-associated olfactory loss in the era of COVID-19 [published
online ahead of print, 2020 Apr 9]. Int Forum Allergy Rhinol.
2020;10.1002/alr.22578. doi:10.1002/alr.22578
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