The coronavirus disease 2019 (COVID-19) is an ongoing viral pandemic that emerged
from East Asia and quickly spread to the rest of the world. This infection is caused
by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Recently, there have
been numerous reports in the media that anosmia occurs in patients who have contracted
coronavirus disease 2019 (COVID-19) by exposure to the SARS-COV-02 virus. The COVID-19
is usually characterized by upper and lower airway symptoms, such as fever, cough,
dyspnea, sputum production, myalgia, arthralgia, headache, diarrhea, rhinorrhea, and
sore throat. However, the spread of the virus worldwide has shown atypical complaints,
such as olfaction and gustatory dysfunction.[1]
[2]
[3]
In Brazil, since February 25th, there have been more than 120,000 infected individuals
and 8,000 deaths until the date the present letter was written on. Self-reported anosmia
has also been quite common in our country. Nowadays, there are a myriad of literature
citations emerging, from single case report to self-reported surveys, from all over
the world on this matter.
Subsequently, a few hypotheses have risen in the past months regarding these symptoms.
Most of the studies have detected an olfactory loss prevalence higher than 60%.[2] One European multicentric survey has shown a prevalence of 85.6% of all the infected
population. The same study showed that 78% of the patients have recovered in at least
8 days[3].
A methodology to decrease response bias from self-reported data is testing subjects
and controls. A study from Iran tested 60 patients with COVID-19 and 60 controls with
the University of Pennsylvania Smell Identification Test. They found that 98% of the
patients reported some degree of olfactory deficit. Although it is hard to test large
sample sizes, this manuscript depicts more precise information regarding the classification
of the chemosensory loss.[2] More extensive sample sizes studies would have detected differences in subgroups
that this article from the Middle East might have failed to do.
Another study from Europe hypothesized that olfactory disturbances could be highly
associated with mild or moderate cases, even with a small sample size.[3] However, there is a lack of evidence that this atypical symptom could serve as a
predictor of severity. Many studies support a high rate of simultaneous taste impairments.
This probably should be secondary to the neuroepithelium damage.
Survey studies usually have a trend to overestimate prevalence. However, most of them
agree that the prevalence of olfactory loss is higher than 60% of cases.[1]
[2]
[3]
[4]
Future studies should clarify whether this chemosensory loss differs according to
COVID-19 severity or hospitalized and non-hospitalized patients. It is important to
emphasize that survey studies, even when using smell validated tests, usually overestimate
prevalence, since subjects with anosmia or hyposmia tend to participate more in these
studies. It is also not known if the recovery rate prevalence or duration varies in
different countries where olfaction habits may vary.
Although the association between olfaction and other nasal symptoms is not established,
there is a weak association among microsmia, nasal obstruction, and rhinorrhea in
this subset of patients.[3]
[4] Another critical topic to be verified is if reporting loss of smell could be a reliable
predictor to mild or moderate COVID-19 infection.[1]
[2]
Small-size surveys could fail to detect differences in subgroups, such as presence
of asthma, chronic nasal symptoms, gender, and age groups. Larger sample size and
well-defined strata would be the main features of the subsequent studies. All the
data collected from observational studies could help us to better understand this
pandemic disease.
Regarding pathophysiology, the severe inflammation due to virus infection still needs
better understanding, and maybe autopsies of patients who died could compare tissue
damage between the olfactory epithelium and the bulb. In addition, the olfactory epithelium
expresses two host receptors, angiotensin-converting enzyme 2 (ACE2) and transmembrane
protease, serine 2 (TMPRSS2) proteases, that facilitate SARS COV 2 binding, replication,
and accumulation. This may be the underlying mechanism for reported cases of smell
dysfunction in patients with COVID 19. It is very likely that these receptors' neurons
initiate the severe inflammation.[6] As a matter of fact, histopathological analysis, including harvesting cadaveric
specimen from both olfactory epithelium and bulb, will help us understand the exact
virus pathway.
Finally, randomized clinical trials should also bring information on therapeutic alternatives,
such as topical drugs, oral corticosteroids, and olfactory training.
