Key points:
Introduction:
Coronavirus disease 2019 (COVID-19) is caused by severe acute respiratory syndrome-corona virus-2 (SARS-CoV-2) infection. COVID-19 has wrought on public health and economic systems worldwide since January 2020. The typical clinical symptoms of COVID-19 are fever, cough, fatigue, headache, myalgia, joint pain, sore throat, olfactory dysfunction (OD), gustatory dysfunction (GD), and diarrhea (1)
In March 2020, Prof C. Hopkins, as President of the British Rhinologi­cal Society, published a letter describing “the loss of sense of smell as a marker of COVID-19 infection” (2) . The European Rhinologic Society also suggested a recommendation about ”loss of smell”, as a significant part of COVID-19 patient symptoms (20-60%). Loss of smell can be the presenting symptom before others (coughing, fever, and dyspnea). Patients with sudden onset olfactory loss should be aware of COVID-19 positive (3) .
In contrast to reports on infection by other viruses, olfactory dysfunction is associated with a relatively good prognosis in COVID-19, which suggests distinct pathological mechanisms that require further clarification (4) .
Olfactory dysfunctions affect the quality of life as patients with olfactory dysfunction encounter problems with cooking, decreased appetite, personal hygiene, social relationships, and emotional problems such as depression, and feeling unsafe as smell also has an important role in detecting warning of dangerous hazards in daily life such as gas, combustion smoke, and chemicals. Women are more likely to experience emotional issues such as depression, anxiety related to olfactory impairment (5) .
The occurrence of post-viral olfactory dysfunction is not new, most commonly occurring with rhinovirus, parainfluenza, Epstein-Barr virus, and some coronaviruses. Many viruses may lead to Olfactory dysfunctions through an inflammatory reaction of the nasal mucosa and further development of rhinorrhea. Follow-up of postviral olfactory loss revealed that over 80% of the patients reported subjective recovery after one year with 35-67% of spontaneous improvement (6) .
Although there is a  large number of studies, the underlying pathophysiological mechanism of anosmia and olfactory dysfunction in COVID-19 remains not fully understood (7) .
It is hypothesized that the SARS-CoV-2 causes loss of smell by entering the supporting neural cells in the olfactory epithelium through the ACE2 receptor (3) .
In response, a rapid autoimmune response activates lymphocytes and macrophages and causes the release of cytokines. This autoimmune response can differ greatly between patients and may explain long-term olfactory disorders. This inflammatory response during COVID-19 is also seen in certain brain areas, along the olfactory pathway (8) .
There are few established interventions for postviral olfactory dysfunction and, although several studies are being conducted, there is currently very little evidence for treatments, specifically for COVID-19-related olfactory dysfunction (7) .
One of the therapeutic options for olfactory disorders in COVID-19 is olfactory training. During it, the patient sniffs a set of known odors daily. Olfactory training may speed up and increase the extent of smell recovery (9) ; however, effects seem limited As the persistent loss of smell is thought to be caused by an inflammatory response. Corticosteroids might be a treatment option. Some studies assessed corticosteroids in nasal spray, without beneficial effect (10) .
Previous studies have investigated the utility of vitamin A in the treatment of olfactory dysfunction, with varying results. The first of these, a case series reported by Duncan and Briggs (11) , reported beneficial effect with high-dose systemic therapy(12) .
Vitamin A could be administered topically and this way should theoretically produce higher localized concentrations at the level of the olfactory epithelium than would be seen with the equivalent dose of systemic therapy (12) .
Effective treatment to correct loss of smell and taste can be established, a biochemical basis for the cause of these symptoms is decreased secretion of several growth factors (cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate (cGMP)) in the saliva and nasal mucus. Growth factors act on stem cells in taste buds and olfactory epithelial cells to generate the elegant repertoire of cellular components in these sensory organs (13) .
Successful treatment with oral theophylline that increased nasal mucus levels of cAMP and cGMP required increased theophylline doses, duration, and endurance of adverse effects, including restlessness, gastrointestinal tract discomfort, sleep difficulties, tachycardia, and other unwanted symptoms. Theophylline treatment also required regular determinations of blood theophylline levels to ensure adequate drug absorption and lack of toxic effects. These efforts limited the use of this orally administered drug (13) .
Efforts to improve therapeutic efficacy and reduce adverse effects of oral theophylline administration made it logical to administer the drug intranasally. So it can affect olfactory receptors more directly without causing the systemic adverse effects associated with oral therapy(14) .
This study evaluates the effectiveness of treatment options for post COVID-19 olfactory dysfunction with nasal steroid, nasal vitamin A and intranasal theophylline.
Patient and methods:
This is a retrospective cohort study of 120 patients at …………………….
Eligibility criteria:
The time periods sampled were ‘pandemic’ (1 January 2020 to 5 may 2022) and ‘post-pandemic’(6 may 2022 to 31 December 2022) with post-COVID-19 olfactory dysfunction (anosmia or hyposmia) who have none of the below-mentioned exclusion criteria.[Table 1]
This study was approved by ………………………………, which approved the study protocol with the approval number RC-17-1-2023. The study was carried out in compliance with the Helsinki Declaration of 1975 and its amendments. A written informed consent form was obtained.
Inclusion and exclusion criteria: shown in [Table 1]
Table 1:Inclusion and exclusion criteria.