Key points:
- Olfactory dysfunctions affect the quality of life as patients
encounter problems with cooking, decreased appetite, personal hygiene,
social relationships.
- The pathophysiological mechanism of anosmia and olfactory dysfunction
in COVID-19 remains not fully understood.
- There is currently very little evidence for treatments, specifically
for COVID-19-related olfactory dysfunction.
- This study evaluates the effectiveness of treatment options for post
COVID-19 olfactory dysfunction with nasal steroid, nasal vitamin A and
intranasal theophylline.
- Combining the usage of topical mometasone furoate or topical vitamin A
or intranasal theophylline with olfactory training shortens the
duration of post-COVID- 19 anosmia/hyposmia.
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.