DISCUSSION
SARS-CoV-2 virus, which is a member of the Coronaviridae family,
contains 4 structural proteins consisting of S (spike), M (membrane) and
N (nucleocapsid, containing the RNA genome) proteins. S protein attaches
to the cell membrane by the angiotensin-converting enzyme-2 (ACE2)
receptor in the host (2,3). SARS-CoV-2 has genetic sequences that are
highly similar to MERS-CoV and SARS-CoV coronaviruses, which are
potentially lethal to humans. The fact that neuroinvasive properties of
these viruses were detected in individuals with MERS and SARS and in
experimental animal studies conducted for these viruses suggests that
the SARS-CoV-2 virus may also have similar properties (4,5).
SARS-CoV-2, enters cells via ACE-2 receptors, which are an important
component of the renin-angiotensin system in the brain, such as SARS-CoV
(6,7).
The olfactory nerve pathway begins with bipolar neurons; their axons and
dendrites go to the olfactory bulb and synapse in this area. In
addition, this pair of cranial nerves are divided into two branches and
heads towards the olfactory nucleus located in the piriform cortex (8).
In the animal models examining coronavirus infection pathways, it has
been shown that the olfactory nerve pathways are used by the virus after
the virus is occluded into the nasal passage (9,10). It has been proven
that the virus reaches the olfactory bulb approximately 60 hours after
its exposure to SARS-CoV-2; it reaches the dorsal nucleus of the raffin
in the piriform cortex and brain stem on the 7th day
(9). The most important aspect of this spreading route is that there is
a possibility that the virus may affect respiratory centers after it has
settled in regions in the brainstem. (9-11).
In their study including 214 patients, Mao et al. evaluated neurological
symptoms in 3 categories as peripheral, central and musculoskeletal. In
this study, neurological symptoms were detected in 77 patients and it
was reported that the symptoms correlated with the severity of the
disease. Imbalance was found in 16.8% and headache was found in 13.1%
in the patients with central nervous system (CNS) symptoms. The most
common symptoms of the peripheral nervous system (PSS) (8.9%) were
hypogusia with 5.6% and hyposmia with 5.1% (4). In the study conducted
by Yan and his team, it was also reported that 71% of COVID-19 positive
patients had loss of smell and taste (12). Menni et al. found that the
rate of loss of smell and taste was 59% in 1702 patients with positive
PCR tests. They also stated that the loss of smell may be one of the
sensitive symptoms for the diagnosis of Covid-19, together with major
symptoms such as fever, cough and shortness of breath (13). In our
study, anosmia developed in 50 (23.5%) patients and hyposmia developed
in 84 (40%)patients. In 3 patients (1.40%), only loss of taste
developed without loss of smell.
Although it is well known that various viruses can damage the olfactory
neuroepithelium, the cause of loss of smell due the SARS-CoV-2 is not
exactly known. Indeed, these acute viral upper respiratory viral
infections that damage the epithelium are the major cause of chronic
olfactory dysfunction, and It is known that a large number of viruses
enter the brain via cellular and pericellular transport through this
epithelium (14). In North America, the highest period of non-flu-related
loss of smell, including those possibly due to coronaviruses, occurs in
April, May, and June while flu-associated loss of smell peaks in
December, January, and February. It is thought that some of the viruses
taken into the body through droplets settle in the lungs through the
respiratory system and form an infection focus while some may settle in
the olfactory epithelium. Also some of the viruses that settle in the
olfactory epithelium are thought to be transported to the central
nervous system via the olfactorius by replicating here (10,14).
In our study, of the patients with nasal steroid 13 patients were using
preparations contatining triamcinolone acetonide, 8 were using
preparations containing fluticasone, and 5 patients were using
preparations containing beclomethasone dipropionate (Table 2).
Remarkably, it was observed that the symptoms related with loss of smell
did not develop in patients using all three preparations. Nasal steroids
prevent the effects of inflammatory cytokines on the nasal mucosa by
suppressing the allergic-inflammatory process both in the early and late
stages. Thus, they prevent the cytokine exposure of olfactory nerve
cells. In addition, since they also suppress the release of mediators
such as histamine that can cause congestion, they mechanically prevent
nasal obstruction. The effects of nasal steroids on loss of smeel have
not been clarified yet. We think that nasal steroids prevent the loss of
smell seen in Covid-19.
We believe that this protective effect occurs due to the fact that the
nasal steroid used plays an immunmodulator role with a local
antinflammatory effect on the nasal mucosa and around the olfactory
nerve.
Although in many studies, loss of smell has been reported based on the
patient’s declaration, Moein et al. compared 60 covid-19 patients with
60 healthy individuals in their UPSIT objective smell test studies and
reported that 58% of patients developed hyposmia (20/60, 33%) or
anosmia (15/60, 25%) (16). As well as our findings are similar to the
results of Moei et al.’s studies with an objective smell test, we
criticize ourselves and our limitations as these findings are based on
data obtained according to subjective patient statements. However,
considering that the primary transmission route of covid-19 is the
droplets, the objective smell test is not recommended at this stage, as
it will increase the risk of contamination of the virus.