Pharmacological Reports (2021) 73:781–785

https://doi.org/10.1007/s43440-021-00235-1

ARTICLE

Evaluation of effects of chronic nasal steroid use on rhinological

symptoms of COVID‑19 with SNOT‑22 questionnaire
Akif İşlek1 · Mustafa Koray Balcı2

Received: 9 November 2020 / Revised: 24 January 2021 / Accepted: 11 February 2021 / Published online: 24 February 2021
© Maj Institute of Pharmacology Polish Academy of Sciences 2021

Abstract
Background The benefits of corticosteroids for the treatment of COVID-19 infection are documented in the literature. The
goal of the study is to compare the severity of rhinological symptoms of COVID-19 between patients with nasal steroid use
(NSU) and the control group (CG) using the sino-nasal outcome test (SNOT-22) questionnaire.
Methods A face-to-face survey was conducted at a second referral state hospital between. Patients with a complete recovery
from COVID-19 were included in NSU and CG groups. Two subscales of the SNOT-22 were filled by the patients. The
frequency and duration of smell and taste loss and SNOT-22 scores were compared between the two groups.
Results Forty-seven patients were included in the study. Thirty-one patients were in CG and 16 patients in the NSU group.
Twenty-four (51.1%) patients were females and 23 (48.9%) were males. The mean age was 41.4 ± 8.6 years. Olfactory dys-
function was detected in 12 (75%) patients in the NSU group, and 31 (93.3%) patients in the control group (CG). Gustatory
dysfunction was seen in 10 (62.5%) patients in the NSU group and 24 (77.4%) patients NSU group. (p = 0.071, 0.279, respec-
tively). The duration of the olfactory (6.6 ± 2.5 days) and gustatory dysfunction (6.1 ± 2.6 days) and the mean SNOT-22 total
score (11.9 ± 1.6) was significantly lower in the NSU group (p < 0.001, CI 11.1–5.1, CI 9.9–4.6, CI 9.3–5.9, respectively).
Conclusions Although nasal steroid use does not prevent olfactory and gustatory dysfunction in COVID-19 patients, it may
reduce the severity and duration of these symptoms.

Keywords COVID-19 · Nasal steroids · allergic rhinitis · SNOT-22 · olfactory dysfunction · Gustatory dysfunction

Introduction especially in the early stages of the disease [2]. The Sino‐
Nasal Outcome Test-22 (SNOT-22) is a widely accepted
The coronavirus disease 2019 (COVID-19) is caused by questionnaire for objective measurement of rhinological
severe acute respiratory syndrome coronavirus 2 (SARS- symptoms of sino-nasal diseases [3]. Also, this questionnaire
CoV-2) and is so far responsible for more than 2 million has been divided into four validated subscales representing
deaths worldwide. The most prevalent symptoms are fever, categorical symptoms: nasal, otologic/facial, sleep-related,
cough, dyspnea, sputum production, myalgia, arthralgia, and emotional symptoms. The validity and reliability of
headache, diarrhea, rhinorrhea, sore throat, loss of olfac- SNOT-22 in the Turkish language have been previously
tory and taste [1]. Olfactory and gustatory dysfunctions confirmed [4].
stand out as important diagnostic symptoms of the COVID- Nasal steroids are frequently used for the treatment of
19 infection which are detected in up to 90% of the cases allergic or non-allergic rhinitis and chronic sinusitis [5, 6].
[1]. Accompanying nasal symptoms are frequently present They decrease the recruitment of inflammatory cells to the
airway mucosa, selectively suppress local cytokine expres-
sion, inhibit mediator release, and support normal mucosal
* Akif İşlek
[email protected] structure [7]. Minshall et al. [7] showed the decrease of focal
metaplasia within the nasal epithelium after long-term use
1
Department of Otorhinolaryngology, Nusaybin State of mometasone by biopsy specimens. Recent studies suggest
Hospital, Mardin, Turkey that nasal steroid treatments should be continued in patients
2
Department of Otorhinolaryngology, İzmir Katip Celebi with allergic rhinitis during COVID-19 pandemic [8].
University Atatürk Training and Research Hospital, İzmir, Besides, stopping oral or inhaled corticosteroid treatments
Turkey

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782 A. İşlek, M. K. Balcı

are not recommended due to the potentially dangerous wors- used for statistics. The study was carried out in accordance
ening of asthma or allergic airway symptoms [8]. The use with the 1964 Helsinki Declaration and subsequent amend-
of nasal corticosteroids for COVID-19-related anosmia or ments. The institutional review board was approved by
ageusia is controversial. In the literatüre, there is a lack of the local Provincial Health Directorate for the study (No:
evidence-based data regarding this topic. 37201737-2/4/2020).
SARS-CoV-2 uses the SARS-CoV receptor ACE2 for
adhesion and entry to the host cell. Recent studies revealed
that ACE2 expression is higher at the nasal mucosa [9, 10]. Results
The ACE2 expression in human nasal epithelial cells is sig-
nificantly suppressed with Dexamethasone, in vitro [10]. Forty-seven COVID-19 patients were included in the
Post-viral olfactory dysfunction is a sensorineural disorder study. Sixteen patients were enrolled in the nasal steroid
and the use of oral or intranasal steroids is a C-level recom- use (NSU) group and 31 patients in CG. Patients were 24
mendation for the treatment [11]. In the current study, we (51.1%) females and 23 (48.9%) males. The mean age was
aimed to test the hypothesis: ’COVID-19 associated nasal 41.4 ± 8.6 years. The most common complains were loss
symptoms will be milder in patients with chronic nasal ster- of smell (n = 41, 87.2%), cough (n = 38, 80.8%), loss of
oid use’. SNOT-22 questionnaire was used for the assess- taste (n = 34, 72.3%), and nasal obstruction (n = 27, 57.4%),
ment of nasal symptoms objectively. We also aimed to evalu- respectively. The olfactory and gustatory functions began to
ate if nasal oral steroid treatment was beneficial for anosmia recover after an average of 11.9 ± 6.1 and 10.8 ± 5.4 days,
or ageusia arising from COVID-19 infection. respectively. The mean total SNOT-22 score was 16.9 ± 4.5
(min: 9, max: 25). Total SNOT-22 scores were significantly
lower in the NSU group and the loss of smell and taste com-
Materials and methods plaints showed earlier improvement in this group (p < 0.001,
Table 1).
The study was designed as a face-to-face survey at a second The mean, standard deviation, and p values of the scores
referral state hospital (Nusaybin State Hospital) between obtained from the questions in the SNOT-22 questionnaire
April 2020 and July 2020. Symptomatic patients with posi- according to the study groups are presented in Table 2. A
tive polymerase chain reaction (PCR +) for SARS-CoV-2 significant positive correlation was detected between the
by nasopharyngeal swabs were included in the study after smell and taste loss complaints and the relevant scale in
complete regression of the symptoms and a negative PCR SNOT-22 (p < 0.001, r = 609 and p = 0.006, r = 397) (Fig. 1).
(−) test. After obtaining verbal and written informed con-
sent, the volunteers were queried and the SNOT-22 was
completed by the patients. Two subscales of the question- Discussion
naire (nasal and otologic/facial pain, Q: 1–12, min. score:0,
max. score: 60) were assessed. Patients were divided into Human CoV was formerly known as a rare cause of post-
two groups according to nasal steroid use (NSU). Patients viral olfactory dysfunction (PVOD) [12]. During the
who had NSU (intranasal mometasone furoate spray, 1 × 200 COVID-19 pandemic, up to 90% association with gusta-
mcg, once in a day) for the last six months for allergic rhini- tory and olfactory dysfunction is reported as an indicative
tis were included in the study group. Patients with a history symptom of the virus infection [1, 13, 14]. In the current
of other regular systemic or topical treatment were excluded. study, taste and smell dysfunctions were also among the
In the control group, patients with a previous history of main symptoms associated with COVID-19. Anamnesis
smell or taste dysfunction, sino-nasal surgery, psychiatric or could not be obtained regarding the initial symptoms of the
neurological diseases, tobacco use, previous trauma, surgery patients, however, taste and smell complaints were the symp-
and/or radiotherapy in head and neck region, pre-existing toms that recovered the latest. Therefore, these patients are
taste or smell dysfunctions, chronic rhinosinusitis with nasal often admitted to the otorhinolaryngology clinic after the
polyposis, and patients younger than 18 years were excluded. regression of the disease.
The demographic data of the patients were recorded. The successful outcomes of systemic and topical steroid
SNOT-22 scores were calculated and the duration of odor treatment for post-viral olfactory dysfunction (PVOD) are
loss was determined. The results were compared between reported in the literature, but the level of evidence is low
the NSU and the control group (CG) using the Mann–Whit- [11]. Sharif-Askari et al. reported downregulating ACE2
ney U and Chi-squared (χ2) test. Spearman Rho Correlation expression in the nasal tissues of patients with chronic rhi-
Coefficient for complaints of smell and taste loss with the nosinüsitis (CRS) after prolonged use of steroids [10]. The
score of odor and taste items in SNOT-22 was calculated. authors suggested the possible protective effect of steroids
SPSS 22.0 program (IBM Corp., Armonk, NY, USA) was during these infections [10]. Nasal steroids are frequently

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Evaluation of effects of chronic nasal steroid use on rhinological symptoms of COVID‑19 with… 783

Table 1  Distribution of the (n, %) CG NSU p

demographic characteristics and
findings of the patients by study χ2
groups
Gender Male 16 51.6 7 43.8 0.609
Female 15 48.4 9 56.3
OD − 2 6.5 4 25.0 0.071
+ 29 93.5 12 75.0
GD − 7 22.6 6 37.5 0.279
+ 24 77.4 10 62.5
(Med, 75%) Mann–Whitney U test
Age 39 48 40 47 0.719
SNOT-22 total 20 22 12 13 < 0.001
Duration of OD 14 18 7 8.5 < 0.001
Duration of GD 13 15 6 8 < 0.001

NSU nasal steroid use, CG control group, OD olfactory dysfunctions, GD gustatory dysfunctions

Table 2  The mean (m), standard deviation (SD), and p values of the Ogimi et al. [20]. demonstrated a significant association
scores obtained from the SNOT-22 questionnaire between prolonged shedding of human coronavirus (HCoV)
CG NSU p* with high-dose steroid use in patients with hematopoietic
cell transplant. Waltl et al. [21] reported that betametha-
m SD m SD
sone may decrease epithelial damage caused by rhinovirus
Need to blow nose 1.5 0.7 .6 0.5 < 0.001 by anti-inflammatory properties on immune cells. Kim et al.
Nasal obstruction 1.6 0.6 1.1 0.6 0.015 [22] showed the in vitro antiviral activity of budesonide via
Sneezing 1.4 0.6 .9 0.6 0.016 inhibiting the human rhinovirus replication by autophagy
Runny nose 1.7 0.7 1.2 0.4 0.009 activation. The authors suggested budesonide as a therapeu-
Cough 2.7 1.0 1.9 0.5 0.004 tic option. In addition, the duration and dose of NSU are not
Postnasal drip 1.4 0.7 0.4 0.5 < 0.001 homogeneous among studies in the literature.
Thick nasal discharge 1.5 0.8 0.4 0.5 < 0.001 However, the number of patients in NSU group was insuf-
Ear fullness 0.5 0.5 0.6 0.5 0.613 ficient to make a reliable conclusion regarding this topic.
Dizziness 0.8 0.4 0.8 0.4 0.764 Besides, it would add value if nasal mucosal changes caused
Ear pain 0.2 0.4 0.1 0.3 0.341 by chronic nasal steroid use was demonstrated histopatho-
Facial pain and/or pressure 2.2 1.0 0.9 0.3 0.011 logically. Although the possible benefits of NSU are tried to
Loss of smell and taste 4.2 1.0 3.1 1.3 0.001 be measured objectively with a questionnaire, the absence
SNOT-22 Total 19.6 3.1 11.9 1.7 < 0.001 of an objective test for the chemosensory function is another
important limitation of our study. In this study, NSU in the
NSU nasal steroid use, CG control group
last 6 months was set as the inclusion criteria, but in prac-
*Mann–Whitney U test
tice, there are different treatment modalities such as 1 year
for perennial rhinitis.
used for the treatment of nasal inflammatory diseases such In accordance with the literature, we observed that the
as allergic rhinitis or CRS [5, 15]. In an experimental ani- nasal steroids may provide milder rhinological symptoms
mal study, a decreased ACE2 expression is shown during and also a shorter recovery in COVID-19 patients. But the
eosinophilic and allergic airway inflammation [16]. Yamaya level of evidence of the current study is low to present any
et al. [17] demonstrated that budesonide reduces rhinovi- suggestions. Prospective and controlled studies with larger
rus count, replication, and concentrations of cytokines of samples would help to provide more valid results regard-
primary cultures of human tracheal epithelial cells. Studies ing the effects of nasal steroids on the nasal mucosa during
evaluating the positive effects of inhaled steroids and sys- COVID-19 infection. Also, the immunohistochemical path-
temic dexamethasone treatment on COVID-19 are reported way of gustatory and olfactory dysfunction in COVID-19
in the recent literature [18, 19]. In the current study, our find- patients is still not clearly understood. Nasal steroids may
ings showed that SNOT-22 total scores were significantly be used for the treatment of the above-mentioned complaints
lower and the loss of smell and taste complaints showed in these patients, but this approach cannot be presented as a
earlier improvement in the NSU group. general recommendation at this stage.

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784 A. İşlek, M. K. Balcı

Fig. 1  Average and total (TS)

SNOT-22 scores in the nasal
steroid use (NSU) and control
group (CG)

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