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.