Abstract
Objective
This study aimed to evaluate the efficacy of corticosteroid irrigation compared to saline to no nasal irrigation in COVID‐19 patients with olfactory loss.
Design and Setting
A randomised controlled study was conducted at the Otolaryngology‐Head & Neck Surgery Department, Ramathibodi Hospital, Faculty of Medicine, Mahidol University.
Participants
Two hundred thirty‐seven COVID‐19 participants with a new‐onset smell loss were recruited into the study. Two hundred twenty‐two participants met the inclusion criteria and were randomised into three groups: corticosteroid irrigation, saline irrigation and no treatment.
Main Outcome Measures
The primary outcome was the mean difference in the smell sensation score among the groups after treatment at 1, 2 and 6 weeks. The secondary outcomes measurements included (1) a self‐rating quality of life (QOL)‐related smell dysfunction score, (2) the change over time in smell sensation score and self‐rating QOL‐related smell dysfunction score and (3) the median time to complete recovery of smell loss.
Results
The mean differences in smell sensation scores among the three groups were not statistically significant at any follow‐up period. The mean score of self‐rating QOL‐related smell dysfunction in the corticosteroid group was significantly better than the other groups at 1 week. The change of outcome scores showed significant improvement over time, regardless of the treatments. The median time to complete smell recovery was similar: 3 weeks.
Conclusion
This study emphasised that corticosteroid nasal irrigation is not superior to saline or no nasal irrigation in restoring the sense of smell in COVID‐19‐associated olfactory loss.
Keywords: corticosteroid irrigation, COVID‐19, nasal irrigation, olfactory dysfunction, post‐COVID smell loss, post‐viral anosmia, post‐viral smell loss, smell loss
Key points.
Olfactory dysfunction is one of the symptoms of COVID‐19, either as the sole presentation or in combination with other symptoms.
The anti‐inflammatory mechanism of corticosteroids has been hypothesised to improve olfactory function.
Previous studies explored corticosteroid nasal spray and drop for post‐COVID smell loss, while corticosteroid nasal irrigation had insufficient information for the treatment in this research area.
This study emphasised that corticosteroid nasal irrigation is not superior to saline or no nasal irrigation in restoring the sense of smell in COVID‐19‐associated olfactory loss by using the subjective olfactory self‐assessment test.
The natural course of the post‐COVID olfactory dysfunction is primarily self‐limiting, and symptoms improve over time.
1. INTRODUCTION
The precise pathophysiology of olfactory loss in coronavirus disease 2019 (COVID‐19) is yet to be determined. However, possible hypotheses are direct virus invasion via the olfactory neuron and the production of inflammatory cytokines resulting in anosmia. 1 , 2 , 3 , 4 The burden of olfactory loss can cause problems in daily life, that is, food ingestion, personal hygiene and hazardous odour detection.
The anti‐inflammatory mechanism of corticosteroids has been hypothesised to improve olfactory function. Many studies have evaluated the efficacy of various intranasal corticosteroids, that is, intranasal spray, drops and irrigation, in post‐COVID‐19 olfactory loss. 5 , 6 , 7 , 8 , 9 The results showed that intranasal corticosteroid spray was not more beneficial than olfactory training on smell function 6 ; however, there may be some advantages when combined with either olfactory training 7 or saline irrigation. 9 While corticosteroid drop did not help shorten the recovery time from COVID‐19 smell loss, 5 one study reported positive outcomes of corticosteroid irrigation on smell function; however, only a small number of participants were included, and multiple medications were also given. 8 Moreover, in previous studies, intranasal corticosteroids were only given to patients with persistent olfactory loss; this delay in treatment omitted the first few weeks after the onset, which could be the golden period to reduce the inflammation of the intranasal olfactory area. We postulated that early treatment in the first week of onset might be beneficial. Therefore, this study aimed to evaluate the efficacy of early use of corticosteroid nasal irrigation compared to saline irrigation and no treatment in COVID‐19 patients with olfactory dysfunction.
2. METHODS
2.1. Study design and setting
This study was a randomised controlled trial conducted at the Otolaryngology‐Head & Neck Surgery Department, Ramathibodi Hospital, Faculty of Medicine, Mahidol University, from July 2021 to December 2021. The study was approved by the ethical committee and conducted following the ethical standards of the Declaration of Helsinki. The reporting trials have been followed the CONSORT guideline. All the patients electronically signed their informed consent before participating in the study.
2.2. Study population
The inclusion criteria were COVID‐19 patients >18 years old with new‐onset of anosmia or hyposmia within 7 days confirmed the reduction in smell sensation scores on the olfactory self‐assessment test. In addition, the patients must prove the COVID‐19‐positive test with the reverse transcription‐polymerase chain reaction technique. The new‐onset of anosmia or hyposmia was defined as patients without prior olfactory loss before COVID‐19 infection. The exclusion criteria included patients who had history of prior olfactory loss, patients who are currently or have been using intranasal or systemic corticosteroids in the past 1 month, patients with chronic rhinosinusitis, sinonasal tumour, anatomical abnormalities of the nose, pregnant women and patients who refused to enrol in the study.
2.3. Randomisation and allocation concealment
The participants were randomly assigned into three groups by a computer‐generated randomised sequence with block size of six. One group of participants did not receive any intervention, one was assigned to saline irrigation and another received corticosteroid nasal irrigation. Sequentially numbered sealed opaque envelopes were provided to the independent investigators. Assessors of the outcome measurements were blinded.
2.4. Study interventions
All participants received six disposable smell test kits, each with four odours, including orange, coffee, jasmine and fish sauce. The odour was contained in a 5‐ml amber glass bottle sealed with plastic wrap to prevent evaporation. The odours were culturally familiar and the concentrations used are equivalent to previous study investigating odour identification in the local normosmia population. 10 In addition, participants in the saline irrigation group received normal saline solution, and patients in the corticosteroid irrigation group received normal saline solution and 14 respules of budesonide (1 mg/2 ml).
Participants in the corticosteroid irrigation group were instructed to prepare a mixture of 1 mg budesonide (1 mg/2 ml) with 500‐ml of normal saline solution and rinse each nostril with 125‐ml of solution twice daily for 2 weeks. The concentration was the same as extensively used in postoperative sinus surgery for chronic rhinosinusitis. 11 Participants in the saline irrigation group rinse each nostril with 125‐ml of normal saline solution twice daily for the same duration.
A quick response code was sent to all participants via mobile phone to scan for an instructional video. The content of the video included how to conduct the smell test, prepare the mixture of corticosteroids and saline solution and demonstrate the rinsing technique. The charge nurses supervised and confirmed the preparation and rinsing technique via face‐to‐face virtual meetings. In addition, the charge nurses took responsibility for reminding and confirming that the participants adhered to the treatments by telephone every 3 days after starting the treatment. All participants were asked to report the outcome measurements via the telephone with the independent blinded assessor at the baseline before starting the treatment and post‐treatment at 1, 2, 3, 4, 5 and 6 weeks.
2.5. Outcome measurements
The primary outcome was the mean difference in the visual analog scale (VAS) score of smell sensation of the four specific odours at 1, 2 and 6 weeks after treatment. The grading scale for each odour ranged from 0, in which the participant had no odour perception, to 10, in which the participant had the best odour perception.
The secondary outcomes included (1) the mean difference in the self‐rating quality of life (QOL)‐related smell dysfunction score at 1, 2 and 6 weeks after treatment, (2) the change over time in smell sensation score and self‐rating QOL‐related smell dysfunction score from the baseline regardless of the treatment interventions, and (3) the median time to complete recovery of smell loss evaluated by the time participants reached the total smell score of four specific odours. In addition, the adverse effects of the treatment interventions, including pharyngeal, nasal burning and pharyngeal, nasal dryness and epistaxis, were collected during the treatment periods. The self‐rating QOL‐related smell dysfunction score used in our study was limited to a disturbance in food ingestion, daily routine and mood because all participants were hospitalised and isolated in the COVID ward in our setting. Thus, the available validated questionnaires might not be appropriate since most questionnaires included questions regarding social anxiety and annoyance in circumstances that the patients did not encounter during the isolation period. The questions used in this study aimed to specifically evaluate the QOL‐related smell dysfunction from COVID‐19 for hospitalised and isolated participants. The questionnaire was listed under Tables 1, 3 and 4; the scores ranged from 0 to 10, with the score of 0 indicating that the smell dysfunction did not disturb the participants' QOL, while the score of 10 indicating maximal disturbance to the participants' QOL.
TABLE 1.
Baseline characteristics
| Group A (corticosteroid irrigation) (n = 72) | Group B (saline irrigation) (n = 70) | Group C (no treatment) (n = 71) | p‐Value | |
|---|---|---|---|---|
| Male (n, %) | 32 (44.44%) | 29 (41.43%) | 29 (40.85%) | .90 |
| Age (mean ± SD) | 33.36 ± 10.38 | 34.97 ± 10.66 | 36.31 ± 11.61 | .27 |
| BMI (mean ± SD) | 23.89 ± 4.99 | 23.80 ± 4.44 | 23.93 ± 4.50 | .99 |
| Smoking (n, %) | .80 | |||
| Current smoking | 9 (12.50%) | 10 (14.29%) | 9 (12.68%) | |
| Previous smoking | 3 (4.17%) | 5 (7.14%) | 2 (2.82%) | |
| Underlying diseases (n, %) | 15 (20.83%) | 20 (28.57%) | 14 (19.72%) | .40 |
| DM (n, %) | 2 (2.78%) | 1 (1.43%) | 3 (4.23%) | .79 |
| Allergic rhinitis (n, %) | 8 (11.11%) | 7 (10%) | 3 (4.23%) | .28 |
| Asthma (n, %) | 0 (0%) | 2 (2.86%) | 1 (1.41%) | .22 |
| Duration of smell loss, days (median [IQR]) | 3 (1–4) | 2 (1–3) | 2 (1–4) | .23 |
| Smell sensation score a at baseline (mean ± SE) | 2.42 ± .23 | 3.20 ± .23 | 2.70 ± .23 | .29 |
| QOL score b at baseline (mean ± SE) | 7.97 ± 2.61 | 7.53 ± 2.82 | 7.97 ± 2.88 | .55 |
| Concomitant symptoms | ||||
| Dysgeusia (n, %) | 27 (37.50%) | 28 (40.00%) | 20 (28.17%) | .30 |
| Fever (n, %) | 43 (59.72%) | 40 (57.14%) | 45 (63.38%) | .75 |
| Chills (n, %) | 8 (11.11%) | 4 (5.71%) | 3 (4.23%) | .24 |
| Malaise/Fatigue (n, %) | 19 (26.39%) | 17 (24.29%) | 16 (22.54%) | .87 |
| Cough (n, %) | 26 (36.11%) | 28 (40.00%) | 32 (45.07%) | .55 |
| Sore throat (n, %) | 28 (38.89%) | 23 (32.86%) | 30 (42.25%) | .51 |
| Headache (n, %) | 13 (18.06%) | 9 (12.86%) | 13 (18.31%) | .62 |
| Nasal congestion (n, %) | 13 (18.06%) | 11 (15.71%) | 9 (12.68%) | .67 |
| Rhinorrhea (n, %) | 18 (25.00%) | 18 (25.71%) | 27 (38.03%) | .16 |
| GI distress (n, %) | 2 (2.78%) | 3 (4.29%) | 2 (2.82%) | .80 |
Smell sensation score was derived from a mean of total smell sensation scores of four specific odours.
QOL score was a self‐rating quality of life‐related smell dysfunction score from the questionnaires. The questionnaires included the following questions, “Does smell loss interfere with any of your ability to taste/enjoy food, make you less aware of personal hygiene (bathing, defecating and urinating), and make you feel depressed, anxious or angry?”
TABLE 3.
The comparison of smell sensation QOL score a at each visit and overall effect among each group
| Group A, corticosteroid irrigation (n = 72) (mean ± SE) | Group B, saline irrigation (n = 70) (mean ± SE) | Group C, no treatment (n = 71) (mean ± SE) | Mean difference (95% CI) | p‐Value | |
|---|---|---|---|---|---|
| QOL score at 1 week | 2.53 ± .21 | 3.17 ± .22 | 3.34 ± .22 | A v B, −.64 (−1.24 to −.04) | .035 |
| A v C, −.81 (−1.41 to −.21) | .008 | ||||
| B v C, −.17 (−.77 to .43) | .59 | ||||
| QOL score at 2 weeks | 1.43 ± .21 | 1.81 ± .22 | 1.69 ± .22 | A v B, −.38 (−.98 to .22) | .21 |
| A v C, −.26 (−.86 to .34) | .39 | ||||
| B v C, .12 (−.48 to .73) | .69 | ||||
| QOL score at 6 weeks | .15 ± .21 | .06 ± .22 | .27 ± .22 | A v B, .10 (−.50 to .69) | .75 |
| A v C, −.11 (−.71 to .48) | .71 | ||||
| B v C, −.21 (−.81 to .39) | .49 | ||||
| Overall QOL score | 1.95 ± .14 | 2.01 ± .15 | 2.18 ± .15 | A v B, −.62 (−.45 to .33) | .76 |
| A v C, −.22 (−.63 to .18) | .27 | ||||
| B v C, −.16 (−.57 to .24) | .43 |
QOL score was a self‐rating quality of life‐related smell dysfunction score from the questionnaires. The questionnaires included the following questions, “Does smell loss interfere with any of your ability to taste/enjoy food, make you less aware of personal hygiene (bathing, defecating and urinating), and make you feel depressed, anxious or angry?”
TABLE 4.
The comparison of the smell sensation score a and QOL score b over time regardless of the treatment interventions
| Mean ± SE | Mean difference from baseline (95% CI) | p‐Value | |
|---|---|---|---|
| Smell sensation score | |||
| Baseline | 2.77 ± .13 | ||
| 1 week | 7.12 ± .13 | 4.35 (4.06–4.64) | <.001 |
| 2 weeks | 8.49 ± .13 | 5.72 (5.43–6.00) | <.001 |
| 3 weeks | 9.20 ± .13 | 6.43 (6.14–6.72) | <.001 |
| 4 weeks | 9.49 ± .13 | 6.72 (6.43–7.01) | <.001 |
| 5 weeks | 9.75 ± .13 | 6.98 (6.69–7.27) | <.001 |
| 6 weeks | 9.82 ± .13 | 7.05 (6.76–7.34) | <.001 |
| QOL score | |||
| Baseline | 7.83 ± .13 | ||
| 1 week | 3.01 ± .13 | −4.82 (−5.09 to −4.54) | <.001 |
| 2 weeks | 1.64 ± .13 | −6.18 (−6.46 to −5.91) | <.001 |
| 3 weeks | .87 ± .13 | −6.96 (−7.24 to −6.68) | <.001 |
| 4 weeks | .49 ± .13 | −7.34 (−7.62 to −7.06) | <.001 |
| 5 weeks | .32 ± .13 | −7.50 (−7.78 to −7.22) | <.001 |
| 6 weeks | .16 ± .13 | −7.67 (−7.94 to −7.39) | <.001 |
Smell sensation score was derived from a mean of total smell sensation scores of four specific odours.
QOL score was a self‐rating quality of life‐related smell dysfunction score from the questionnaires. The questionnaires included the following questions, “Does smell loss interfere with any of your ability to taste/enjoy food, make you less aware of personal hygiene (bathing, defecating and urinating), and make you feel depressed, anxious or angry?”
2.6. Statistical analysis
The sample size was estimated based on self‐reported olfactory function scores before treatment, as previously reported by Yildiz et al., 9 using a type I error of .05 and a power of .8. The authors consider the sample size of 207 in total numbers as the most appropriate and feasible to detect a significant difference between groups. Further data loss was estimated at 15%; the final estimation was approximately 240.
The outcomes were compared using a linear mixed‐effects model for analysis. The median time to complete recovery from smell loss was described by survival analysis. The adverse effects from the treatments were reported in risk ratios. All analyses were performed using Stata version 17.0 (StataCorp). All test statistics were reported in terms of the magnitude of effect with mean difference and 95% confident interval (CI), where a p‐value of less than .05 was considered statistically significant.
3. RESULTS
3.1. Participant flow and baseline characteristics
Two hundred thirty‐seven participants were enrolled in the study. However, 15 participants were excluded, one took systemic corticosteroid and 14 refused to enrol in the study. The remaining two hundred twenty‐two participants were randomised to receive corticosteroid irrigation (n = 74), saline irrigation (n = 74) and no treatment (n = 74). Nine participants lost follow‐up, and there were 72 participants in the corticosteroid irrigation group, 70 in the saline irrigation group and 71 in the untreated group for the final analysis (Figure 1). Of these participants, the baseline characteristics were balanced among the three groups, as shown in Table 1.
FIGURE 1.
CONSORT flowchart showing patient recruitment and assignment
3.2. Primary outcome
The mean differences in smell sensation score in the corticosteroid group (group A) and saline group (group B) were not statistically significant compared to the untreated group (group C) at any of the follow‐up time points (mean difference between group A and C at 1 week = .14, p‐value = .66, at 2 weeks = .36, p‐value = .27 and at 6 weeks = .19, p‐value = .56, and mean difference between group B and C at 1 week = −.56, p‐value = .86, at 2 weeks = −.16, p‐value = .63 and at 6 weeks = .13, p‐value = .7). The mean difference in the smell sensation score between the corticosteroid and the saline groups was not statistically significant (mean difference between groups A and B at 1 week = .2, p‐value = .55, at 2 weeks = .51, p‐value = .12 and 6 weeks = .06, p‐value = .85) (Table 2).
TABLE 2.
The comparison of smell sensation score a at each visit and overall effect among each group
| Group A, corticosteroid irrigation (n = 72) (mean ± SE) | Group B, saline irrigation (n = 70) (mean ± SE) | Group C, No treatment (n = 71) (mean ± SE) | Mean difference (95% CI) | p‐Value | |
|---|---|---|---|---|---|
| Smell sensation score at 1 week | 7.24 ± .23 | 7.04 ± .22 | 7.10 ± .23 | A v B, .20 (−.44 to .84) | .55 |
| A v C, .14 (−.50 to .78) | .66 | ||||
| B v C, −.56 (−.70 to .59) | .86 | ||||
| Smell sensation score at 2 weeks | 8.77 ± .23 | 8.26 ± .23 | 8.42 ± .23 | A v B, .51 (−.12 to 1.15) | .12 |
| A v C, .36 (−.28 to .99) | .27 | ||||
| B v C, −.16 (−.80 to .48) | .63 | ||||
| Smell sensation score at 6 weeks | 9.91 ± .23 | 9.85 ± .23 | 9.72 ± .23 | A v B, .06 (−.58 to .70) | .85 |
| A v C, .19 (−.45 to .82) | .56 | ||||
| B v C, .13 (−.51 to .77) | .70 | ||||
| Overall smell sensation score | 8.17 ± .16 | 8.13 ± .16 | 7.97 ± .16 | A v B, .04 (−.34 to .42) | .85 |
| A v C, .20 (−.24 to .64) | .38 | ||||
| B v C, .16 (−.28 to .61) | .47 |
Smell sensation score was derived from a mean of total smell sensation scores of four specific odours.
3.3. Secondary outcomes
There was a significantly greater improvement in the self‐rating QOL‐related smell dysfunction score in the corticosteroid group compared to the saline group and the untreated group at 1 week after treatment (mean difference between group A and B = −.64, p‐value = .035 and mean difference between group A and C = −.81, p‐value = .008). The mean difference in self‐rating QOL‐related smell dysfunction score between the saline and untreated groups was not statistically significant (mean difference between groups B and C = −.17, p‐value = .59). The mean differences in self‐rating QOL‐related smell dysfunction scores among the three groups were not statistically significant at 2‐ and 6‐week follow‐ups (Table 3).
The smell sensation score and self‐rating QOL‐related smell dysfunction score significantly improved over time from the baseline in all three groups, regardless of the intervention, as shown in Table 4.
There was an equal median time to complete recovery of smell loss at 3 weeks in all three groups (Figure 2).
FIGURE 2.
Kaplan–Meier curves comparing time to complete recovery of smell loss among three treatment groups. There was an equal median time to complete recovery of smell loss at 3 weeks in all three groups. Group A, corticosteroid irrigation; Group B, saline irrigation; Group C, no treatment
There was no difference in all the adverse effects among the three groups; however, the group receiving corticosteroid irrigation had significantly lower nasal dryness with a risk reduction of 77% compared to the untreated group (risk ratio; .23, 95% CI: .10–.53, p = .01) (Table 5).
TABLE 5.
The adverse effects of each treatment compare to no treatment
| Side effects | Risk ratio | 95% CI | p‐Value |
|---|---|---|---|
| Pharyngeal burning | |||
| No treatment | 1.00 | ||
| Corticosteroid irrigation | .86 | .31–2.37 | .77 |
| Saline irrigation | 1.45 | .54–3.84 | .46 |
| Nasal burning | |||
| No treatment | 1.00 | ||
| Corticosteroid irrigation | .66 | .35–1.25 | .20 |
| Saline irrigation | .92 | .50–1.67 | .78 |
| Pharyngeal dryness | |||
| No treatment | 1.00 | ||
| Corticosteroid irrigation | .80 | .39–1.66 | .55 |
| Saline irrigation | 1.30 | .65–2.63 | .46 |
| Nasal dryness | |||
| No treatment | 1.00 | ||
| Corticosteroid irrigation | .23 | .10–.53 | .001 |
| Saline irrigation | .56 | .28–1.11 | .10 |
4. DISCUSSION
Olfactory dysfunction has been accepted as one of the common presentations of COVID‐19, either as the sole symptom or in combination with other symptoms, particularly in the early pandemic. The treatments of olfactory dysfunction include non‐therapeutic agents, that is, olfactory training, acupuncture and therapeutic agents, that is, corticosteroids and non‐corticosteroids therapy. The current systematic review revealed that olfactory training is an efficient therapy for post‐viral olfactory dysfunction. 12 , 13 However, its benefit was established as a rehabilitative intervention in patients with prolonged symptoms.
One pilot study evaluated a short course of systemic corticosteroids with olfactory training in 27 participants who had persistent olfactory dysfunction after COVID‐19 infection. 14 The authors reported a significantly improved smell function. However, recent evidence raised a concern that systemic corticosteroids may delay viral clearance. 15 , 16 Thus, some publications did not recommend prescribing systemic corticosteroids, particularly in active cases. 17 , 18 , 19
Abdelalim et al. showed that corticosteroid nasal spray was not superior to olfactory training. 6 Conversely, few studies used corticosteroid nasal spray as a combined treatment with other interventions and found some significant advantages. These included the study by Kasiriet et al., in which the authors reported a more significant improvement in smell perception on VAS when adding corticosteroid nasal spray to olfactory training; nevertheless, this did not significantly affect the validated standard smell identification test (Iran‐SIT) compared to the placebo group. 7 Another study was done by Yildiz et al., whereby the authors reported a more significant positive effect of a combined treatment of saline irrigation plus corticosteroid nasal spray on the self‐rating olfactory score and olfactory dysfunction duration than the treatment with saline irrigation alone and without any treatment. 9
One study showed no difference in the olfactory recovery time between the group using corticosteroid nasal drops and placebo. 5 Vaira's study was the only publication that evaluated corticosteroid nasal irrigation's effect on olfactory loss in 18 COVID‐19 patients. 8 The authors reported a significant improvement in olfactory function at 20 and 40 days after treatment compared to the untreated patients. However, multiple interventions, including systemic corticosteroids, corticosteroid nasal irrigation, mucolytic, and decongestant, were given in the study. Therefore, it is difficult to ensure that the positive effect was established explicitly from the corticosteroid nasal irrigation alone. Moreover, the study had a small sample size, reducing the likelihood that a statistically significant result reflected the actual effect. Eventually, the authors remarked that the earlier the start of the treatment, the higher the chance of gaining full olfactory recovery.
To the best of our knowledge, the present study is the first trial to determine the actual effect of corticosteroid nasal irrigation on post‐COVID‐19 smell loss. The study's strength rests on the randomised controlled design with saline irrigation alone and without treatment to ensure that the improvement of the symptoms resulted from corticosteroid nasal irrigation.
The early use of corticosteroid nasal irrigation was hypothesised to help wash out inflammatory cytokines and reduce mucosal inflammation. However, our study revealed no significant improvement in smell sensation in all three groups. These results favour the theory of direct damage of olfactory neuroepithelium rather than an inflammatory reaction of the nasal mucosa as the pathophysiology of post‐COVID olfactory loss. This pathological hypothesis was supported by earlier data that COVID‐19 patients commonly presented with acute smell loss without other sinonasal symptoms. 20 , 21 In addition, this study emphasises that post‐COVID‐19 olfactory loss is primarily self‐limited with improvement over time, regardless of the treatment. The median time to full smell recovery in this study was similar at the third week among the treatments. Neuron regeneration theory might explain this functional recovery, which typically occurs after a few weeks of injury onset. 22 , 23
In this study, the early use of corticosteroid nasal irrigation slightly improved QOL in the first week. These data joined the experts that topical corticosteroids might improve nasal symptoms and QOL but had no effect on olfaction. 24 The QOL improvement may be reasonably meaningful for most COVID‐19 patients since they have never experienced smell loss before, and the symptom can lead to anxiety and depression. However, this positive outcome should be interpreted carefully due to potential bias from the unblinded participants. In addition, the effect might be indirectly influenced by the significant reduction of nasal dryness from applying corticosteroid nasal irrigation.
The limitation of this study was that the follow‐up periods were insufficient to provide further information on the prevalence of patients with persistent olfactory dysfunction among the treatments. In addition, there is currently no standardised psychophysical olfactory test in many countries, including in our setting, which may decrease the reliability of the olfactory assessment in this study. Therefore, the bottom line is that the outcomes in this study might not represent the same effects when using the standardised psychophysical olfactory test. From the results of our study, we conclude that corticosteroid nasal irrigation for COVID‐19 smell loss is still questionable and needs further study on the validated outcome measurements, safety profiles and cost‐effectiveness of the treatment.
5. CONCLUSION
This study emphasised that corticosteroid nasal irrigation is not superior to saline or no nasal irrigation for restoring the sense of smell in COVID‐19‐associated olfactory loss by using the subjective olfactory self‐assessment test. The natural course of the olfactory dysfunction is primarily self‐limiting, and symptoms improve over time, regardless of treatment.
AUTHOR CONTRIBUTIONS
Jidapa Tragoonrungsea designed study and methodology, performed experiments, collected and analysed the data, interpreted the results and wrote the manuscript. Navarat Tangbumrungtham reviewed the study design and methodology, critically appraised, edited English language and proved the final manuscript. Tuleeya Nitivanichsakul reviewed the study design and methodology, critically appraised and proved the final manuscript. Boonsam Roongpuvapaht reviewed the study design and methodology, critically appraised and proved the final manuscript. Kangsadarn Tanjararak was a corresponding author and main supervisor of the study, presented the idea, reviewed the study design and methodology, performed experiments, analysed the data, wrote the manuscript, critically appraised and proved the final manuscript. All authors discussed the results and approved the final manuscript.
FUNDING INFORMATION
This research was supported by Faculty of Medicine, Ramathibodi Hospital, Mahidol University, a not‐for‐profit sector.
CONFLICT OF INTEREST
All authors declare that they have no financial disclosures and conflict of interest.
ETHICS STATEMENT
The study was approved by the local ethical committee (COA. MURA2021/535) and was conducted in accordance with the ethical standards of the Declaration of Helsinki. The reporting trials have followed the CONSORT guideline.
ACKNOWLEDGMENTS
The authors thank Sukanya Siriyotha, biostatistician at Department of Clinical Epidemiology and Biostatistics, Ramathibodi Hospital, Faculty of Medicine, Mahidol University, for assistance with statistical analysis in this study.
Tragoonrungsea J, Tangbumrungtham N, Nitivanichsakul T, Roongpuvapaht B, Tanjararak K. Corticosteroid nasal irrigation as early treatment of olfactory dysfunction in COVID‐19: A prospective randomised controlled trial. Clinical Otolaryngology. 2022. 10.1111/coa.14004
Funding information Faculty of Medicine, Ramathibodi Hospital, Mahidol University
DATA AVAILABILITY STATEMENT
The data generated and analyzed during the study are available from the corresponding author on reasonable request.
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Associated Data
This section collects any data citations, data availability statements, or supplementary materials included in this article.
Data Availability Statement
The data generated and analyzed during the study are available from the corresponding author on reasonable request.