|Year : 2021 | Volume
| Issue : 3 | Page : 162-165
Role of oral corticosteroid and olfactory training for treatment of Post-COVID-19 olfactory dysfunction: Our experiences
Santosh Kumar Swain1, Somya Ranjan Pani2
1 Department of Otorhinolaryngology and Head and Neck Surgery, IMS and SUM Hospital, Siksha “O&
#8221; Anusandhan University, Bhubaneswar, Odisha, India
2 Department of Otorhinolaryngology and Head and Neck Surgery, IMS and SUM Hospital, Siksha “O” Anusandhan University, Bhubaneswar, Odisha, India
|Date of Submission||21-Jun-2021|
|Date of Acceptance||02-Aug-2021|
|Date of Web Publication||30-Aug-2021|
Santosh Kumar Swain
Department of Otorhinolaryngology and Head and Neck Surgery, IMS and SUM Hospital, Siksha “O” Anusandhan University, K8, Kalinga Nagar, Bhubaneswar - 751 003, Odisha
Source of Support: None, Conflict of Interest: None
Background: Coronavirus disease 2019 (COVID-19) infection is highly contagious and the increasing number of patients with variety of symptoms. Olfactory loss is currently a well-recognized symptom of COVID-19 infection. Many patients with COVID-19 infections recover with their normal sense of smell after few weeks, however certain portion of them develop long-standing olfactory dysfunction. Objective: The objective is to study the role of oral corticosteroids and olfactory training (OT) as a treatment for olfactory dysfunction in COVID-19 patient. Materials and Methods: This is a prospective and descriptive study on 78 COVID-19 patients who administered oral corticosteroids and OT. All of them were diagnosed with COVID-19 infection by reverse transcription polymerase chain reaction of nasopharyngeal swab. The detail clinical examination and treatment with intranasal corticosteroid and its outcome were analyzed. Results: In this study, 46 (58.97%) patients were male and 32 (41.02%) were female with male to female ratio of 1.43:1. The age ranges of 18–62 years. There were 36 (46.15%) patients in the age range of 18–30 years, 42 (53.84%) patients in the age range of 31–62 years. Out of 78 patients, 11 (14.10%) patients were recovered after 2 weeks, 34 (43.58%) patients recovered after 3 weeks, and 24 (30.76%) recovered after 4 weeks. Three patients lost follow-up during the treatment period. Conclusion: Combination of short course of oral corticosteroids and OT is a beneficial and safe treatment option for COVID-19 patients with olfactory dysfunction. However, there is a crucial demand for further studies to corroborate this outcome.
Keywords: Coronavirus disease 2019, olfactory dysfunction, olfactory training, oral corticosteroid, severe acute respiratory syndrome corona virus 2
|How to cite this article:|
Swain SK, Pani SR. Role of oral corticosteroid and olfactory training for treatment of Post-COVID-19 olfactory dysfunction: Our experiences. Apollo Med 2021;18:162-5
| Introduction|| |
Coronavirus disease 2019 (COVID-19) is a rapidly spreading infection caused by severe acute respiratory syndrome corona virus 2 (SARS-CoV-2) which affected whole world in just few months. Currently, COVID-19 infection is a threat to the global health. The first case of COVID-19 was identified in Wuhan, China, in early part of December 2019. SARS-CoV-2 is the seventh member of the coronaviridae family, a positive RNA virus, known to affect the respiratory tract of the human being. The clinical manifestations of the COVID-19 infection include fever, dry cough, myalgia, dyspnea, olfactory dysfunction, and gustatory dysfunction. The loss of smell by COVID-19 infection is more prevalent and severe than any other viral upper respiratory tract infections. The exact cause of olfactory dysfunction in COVID-19 patient is still unclear. The recovery rate of olfactory dysfunction varies significantly which ranges from 4% to 89% a month after onset of anosmia or hyposmia. Longstanding olfactory loss may result in different comorbidities such as impaired cognition, depression, and even from earlier death. Currently, there is no standard medical intervention for persistent olfactory dysfunction of COVID-19 patients, although the olfactory training (OT) has been suggested. In the beginning of the COVID-19 pandemic, the World Health Organization (WHO) strongly avoided the use of oral corticosteroids; however, increasing evidence shows that significant benefit on mortality in severe type of COVID-19 patients. The benefit of the oral corticosteroid may be observed if treated at an early stage of the infection. Currently, very less studies have been done for use of oral corticosteroids and OT in COVID-19 patients with persisting olfactory dysfunction. Here, this study is aimed to evaluate the role of oral corticosteroid along with OT for post-COVID-19 olfactory dysfunction.
| Materials and Methods|| |
This is a prospective study conducted at a tertiary care teaching hospital between the April 2020 and May 2021. This study was approved by Institutional Ethical Committee (IEC) with reference number IEC/IMS/SOAU//24/10.04.2020. The patients those recovered from proven COVID-19 infection and complaining anosmia or hyposmia were enrolled in this study. The proven COVID-19 positive patient was based on the positive real-time reverse transcriptase polymerase chain reaction (RT-PCR) where samples were obtained from the nasopharyngeal swab. The recovery was defined as negative report of RT-PCR. The patients those participated in this study were above the age of 18 years. All of them had complained of decreased smell sensation. Patients with previous sinonasal disease, already using topical or oral steroid, pregnancy and patients those with hyposmia/anosmia improved before COVID-19 recovery were excluded from this study. Patients with diabetes mellitus, hypertension, glaucoma, psychotic disorders, peptic ulcers, immunosuppressive conditions such as AIDS and patients under chemotherapy are excluded from this study. All the enrolled patients were signed their written informed consents for this study. All participants underwent detailed medical examination and past relevant history documented such as age, sex, duration, severity of the COVID-19 infection, and place of isolation/treatment. The clinical examinations of the participants were done with use of appropriate protective measures. All the participants received a 10 days' course of 16 mg methylprednisolone twice daily combined with OT. All the participants were advised to sniff the rose, clove, and lemon for 20 s each, twice a day. The assessment of smell was done after 1 week, after 2 weeks, after 3 week, after 4 weeks, and after 6 weeks for all patients. The duration of decreased smell was documented from the onset of hyposmia/anosmia till full recovery of the sensation.
Statistical Package for the Social Science (SPSS) Statistics for Windows, version 20, was used for all statistical analyses (IBM-SPSS Inc., Chicago, IL, USA).
| Results|| |
In this prospective study, 78 (26.71%) patients presented with olfactory dysfunction out of the 292 COVID-19 patients. Out of 78 patients, 46 (58.97%) was male and 32 (41.02%) were female with male to female ratio of 1.43:1. The age ranges of 18–62 years with a mean age of 31.42 years. There were 36 (46.15%) patients in the age range of 18–30 years, 42 (53.84%) patients in the age range of 31–62 years [Table 1]. Out of 78 patients, 44 (56.41%) patients were managed in home isolation and 34 (43.58%) were managed in hospital. Out of 78 patients, 11 (14.10%) patients recovered by 2 weeks, 34 (43.58%) patients recovered by 3 weeks and 24 (30.76%) recovered after 4 weeks, 6 (7.69%) patients recovered by 6 weeks [Table 2]. Three patients lost follow-up during the treatment period. All of the patients underwent OT during treatment period along with oral corticosteroids. All patients revived their olfaction by 6 weeks except three patients those lost follow-up. Out of 78 patients, 5 (6.41%) reported minimal side effects such as abdominal pain. No patients reported side effects to OT.
|Table 1: Clinical profile of patients with post-COVID olfactory dysfunction|
Click here to view
|Table 2: Treatment output of patients with post-COVID olfactory dysfunction|
Click here to view
| Discussion|| |
COVID-19 pandemic was originated from Wuhan, Hubei Province, China, and rapidly spread to worldwide. Patients with COVID-19 infection present with wide ranges of symptoms such as fever, myalgia, dry cough, olfactory dysfunction, gustatory dysfunction to acute respiratory distress syndrome, and respiratory failure. Viral upper respiratory tract infection is one of the most common causes for olfactory dysfunction. Viruses those cause upper respiratory tract infections or common cold followed by olfactory dysfunction include influenza, parainfluenza virus, rhinovirus, and coronavirus. COVID-19 pandemic is still ongoing and several patients keep on complaining olfactory dysfunction. Olfactory dysfunction is characteristic feature of COVID-19 patients which may be only symptom or associated with other symptoms, but its exact pathogenesis is not clear. The olfactory dysfunction in COVID-19 patients may result from viral induced olfactory nerve damage, local inflammation in the nasal cavity or both. In COVID-19 infection, the SARS-CoV-2 may damage the olfactory epithelium and alter the number and functions of its receptors. It is a hypothesis that the olfactory dysfunctions are not related with viral damage to the neuronal cells. Nonneuronal cells which express angiotensin converting enzyme 2 (ACE2) receptors such as olfactory epithelium sustentacular cells, Bowman's gland cells, microvillar cells, horizontal basal cells and olfactory bulb pericytes may be the target cells for SARS-CoV-2. In case of long-standing olfactory dysfunction, the involvement of the stem cells which express fewer ACE2 receptors could be considered as the etiology. However, the exact etiopathogenesis for underlying chemosensitive dysfunctions in COVID-19 patients has not been elucidated.
The olfactory dysfunction is divided into two types such as conductive type (physical blockage of the airflow into the olfactory mucosa) and sensorineural type (damage of the olfactory neural signaling pathway). The exact cause for sensorineural type of olfactory dysfunction is still not known.
The prognosis of sensorineural type of olfactory dysfunction is poor and also irreversible. Postviral olfactory dysfunction also shows poor response to treatment. If the sensorineural type of olfactory dysfunction recovers, the majority of the cases show improvement within 6 months. One study shows sensorineural type of the olfactory dysfunction may not show an effective outcome to the oral or topical steroids. Although most of the patients with olfactory dysfunction are getting recovery to normal olfaction after few weeks of infection, a small group of patients are presenting persistent olfactory dysfunction with symptoms such as anosmia, hyposmia, parosmia, and phantosmia. In this study, recovery of olfaction of all patients occurred by 6 weeks.
Olfactory dysfunction has significant impact on quality of life. Many cases of COVID-19 infection with olfactory dysfunction recover by 7–14 days and approximately 10% of cases present with severe olfactory impairment and persists beyond the first 4–6 weeks. In this study, 14.10% patients recovered by 2 weeks, 43.58% patients recovered by 3 weeks, 30.76% recovered after 4 weeks, and 7.69% patients recovered by 6 weeks. One study showed that olfactory function was more affected in COVID-19 patients than common cold. Although majority of the COVID-19 patients with olfactory dysfunction get recovery from this symptom, certain proportion of patients will develop permanent olfactory dysfunction. One study in Italy showed olfactory disturbance in COVID-19 patients are often seen in younger patients and in women. In this study, patients were in the age group of 18–62 years and a greater number of patients (53.84%) with olfactory dysfunction specifically in 31–62 years followed by 46.15% in the age group of 18–30 years.
Proper history taking from the patient, endoscopic examination of the nasal cavity and imaging are important parts for diagnosis of the suspected olfactory dysfunction following COVID-19 infection. The requirement of imaging in COVID-19 patient has yet to be established, and so should be reserved for patients with persistent olfactory dysfunction. Computed tomography scan is useful to evaluate the sinonasal pathology. Magnetic resonance imaging is an important imaging to find out the lesion on the olfactory epithelium. Several medications have been tried for the treatment of the postviral olfactory dysfunction and these include oral corticosteroid, intranasal corticosteroids, alpha lipoic acid, zinc sulfate, theophylline, caroverine, Vitamin A, Gingko biloba, sodium citrate, and minocycline. However, the evidence supporting the use of these medications for postviral olfactory dysfunction is limited and no large randomized controlled trials done to support this treatment.
Oral corticosteroids are usually administered in different otorhinolaryngological conditions such as idiopathic sudden sensorineural hearing loss, sudden onset facial nerve palsy, and acute postviral anosmia. Steroid administration is often associated with hearing improvement in case of sudden onset sensorineural hearing loss whereas an improvement in case olfactory recognition suggests that corticosteroids may be useful for acute, reversible stages of olfactory mucosal injury in case of acute postviral anosmia. Exogenous steroids have been classically associated with suppression of the body immunity. Hence, during COVID-19 pandemic the use of corticosteroids should be judicious as it has negative impact on innate immunity, so limit the first line of defense and increase the viral load. However, the adaptive immunity should also be taken into consideration with regard to COVID-19 immunopathology and coincides with appearance of specific antibody against SARS-CoV-2. However, steroid therapy in COVID-19 patients shows low mortality rates and increase survival., One study showed that systemic corticosteroids improve the smell sensation in viral upper respiratory tract infections. In initial period of pandemic, oral corticosteroids were strongly contraindicated by the WHO; however, mounting evidence presenting significant benefit on mortality in severe type of COVID-19 infection. One study was showing that improvement of the olfaction with use of systemic corticosteroid in some patients with postviral olfactory dysfunction. OT is another important treatment option for olfactory dysfunction and is successful in patients with loss of smell sensation after upper respiratory tract infection. Although outcome of an OT program is under investigation, the neuronal basis of this treatment remains poorly understood. In post-COVID-19 olfactory dysfunction, few supportive medications include intranasal sodium citrate which thought to modulate the olfactory receptor transduction cascades, intranasal Vitamin A which may act as promotor for olfactory neurogenesis and systemic omega-3 which usually act through neurodegenerative or anti-inflammatory means. The latter two medications may act as adjuvant therapies in OT. However, till date, there is no documentation regarding effectiveness of therapies in OT. However, currently, there is no evidence of these therapies are effective in COVID-19 patients.
| Conclusion|| |
Normal sense of smell is needed for the human being to identify the chemical signals from surroundings. Any abnormality in sensation of smell affects the quality of life. Hyposmia or anosmia is common clinical symptoms found in COVID-19 patients. Early treatment of olfactory dysfunction in post-COVID patient helps to protect quality of life. Oral corticosteroid is an important treatment option in the current scenario for preventing olfactory dysfunction. OT along with oral corticosteroids increases the chance of recovery from olfactory impairment. However, more studies are required to known more treatment options for post-COVID olfactory dysfunction. There are also a greater number of studies are required to validate our findings and find out other treatment options for avoiding longstanding sensorineural type of olfactory dysfunctions.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| References|| |
Swain SK, Jena PP. Clinical implications and future perspective of COVID-19 pandemic – A review. Int J Adv Med 2021;8:334-40.
Swain SK, Kumar S. Infection control measures during COVID-19 pandemic – An otorhinolaryngological and head-and-neck perspective. Indian J Health Sci Biomed Res (KLEU) 2021;14:3-11.
Boscolo-Rizzo P, Borsetto D, Fabbris C, Spinato G, Frezza D, Menegaldo A, et al
. Evolution of altered sense of smell or taste in patients with mildly symptomatic COVID-19. JAMA Otolaryngol Head Neck Surg 2020;146:729-32.
Hura N, Xie DX, Choby GW, Schlosser RJ, Orlov CP, Seal SM, et al
. Treatment of post-viral olfactory dysfunction: An evidence-based review with recommendations. Int Forum Allergy Rhinol 2020;10:1065-86.
Whitcroft KL, Hummel T. Olfactory dysfunction in COVID-19: Diagnosis and management. JAMA 2020;323:2512-4.
Mattos-Silva P, Felix NS, Silva PL, Robba C, Battaglini D, Pelosi P, et al
. Pros and cons of corticosteroid therapy for COVID-19 patients. Respir Physiol Neurobiol 2020;280:103492.
Miwa T, Ikeda K, Ishibashi T, Kobayashi M, Kondo K, Matsuwaki Y, et al
. Clinical practice guidelines for the management of olfactory dysfunction – Secondary publication. Auris Nasus Larynx 2019;46:653-62.
Swain SK. Sudden onset of olfactory and gustatory dysfunction – An early predictor to isolate the patient in COVID-19 pandemic. Indian J Health Sci Biomed Res (KLEU) 2021;14:173-7.
Swain SK, Pani SR. Incidence of hearing loss in COVID-19 patients: A COVID hospital-based study in the eastern part of India. Int. J Curr Res Rev 2021;13:103-7.
Suzuki M, Saito K, Min WP, Vladau C, Toida K, Itoh H, et al
. Identification of viruses in patients with postviral olfactory dysfunction. Laryngoscope 2007;117:272-7.
Hummel T, Whitcroft KL, Andrews P, Altundag A, Cinghi C, Costanzo RM, et al
. Position paper on olfactory dysfunction. Rhinology 2016;56:1-30.
Swain SK, Behera IC. Managing pediatric otorhinolaryngology patients in coronavirus disease-19 pandemic – A real challenge to the clinicians. Indian J Child Health 2020;7:357-62.
Swain SK, Agrawala R. Mastoid surgery: A high-risk aerosol generating surgical procedure in COVID-19 pandemic. Int J Otorhinolaryngol Head Neck Surg 2020;6:1941-6.
Meng X, Deng Y, Dai Z, Meng Z. COVID-19 and anosmia: A review based on up-todate knowledge. Am J Otolaryngol 2020;41:102581.
Tian J, Pinto JM, Li L, Zhang S, Sun Z, Wei Y. Identification of viruses in patients with postviral olfactory dysfunction by multiplex reverse-transcription polymerase chain reaction. Laryngoscope 2021;131:158-64.
Sungnak W, Huang N, Bécavin C, Berg M. HCA Lung Biological Network. SARS-CoV-2 entry genes are most highly expressed in nasal goblet and ciliated cells within human airways. ArXiv 2020;26:681-7.
Swain SK. Smell and taste abnormalities: Early clinical biomarkers for isolating the positive cases in COVID-19 pandemic. Int J Otorhinolaryngol Head Neck Surg 2021;7:196-201.
Cho SH. Clinical diagnosis and treatment of olfactory dysfunction. Hanyang Med Rev 2014;34:107-15.
Swain SK, Acharya S, Sahajan N. Otorhinolaryngological manifestations in COVID-19 infections: An early indicator for isolating the positive cases. J Sci Soc 2020;47:63-8. [Full text]
Hummel T. Perspectives in olfactory loss following viral infections of the upper respiratory tract. Arch Otolaryngol Head Neck Surg 2000;126:802-3.
Le Bon SD, Pisarski N, Verbeke J, Prunier L, Cavelier G, Thill MP, et al
. Psychophysical evaluation of chemosensory functions 5 weeks after olfactory loss due to COVID-19: A prospective cohort study on 72 patients. Eur Arch Otorhinolaryngol 2021;278:101-8.
Hopkins C, Surda P, Whitehead E, Kumar BN. Early recovery following new onset loss of sense of smell during the COVID-19 pandemic – An observational cohort study. J Otolaryngol Head Neck 2020;49:26.
Huart C, Philpott C, Konstantinidis I, Altundag A, Whitcroft KL, Trecca EM, et al
. Comparison of COVID-19 and common cold chemosensory dysfunction. Rhinology 2020;58:623-5.
D'Ascanio L, Pandolfini M, Cingolani C, Latini G, Gradoni P, Capalbo M, et al
. Olfactory dysfunction in COVID-19 patients: Prevalence and prognosis for recovering sense of smell. Otolaryngol Head Neck Surg 2021;164:82-6.
Swain SK, Das S, Lenka S. Sudden sensorineural hearing loss among COVID-19 patients-our experiences at an Indian teaching hospital. Siriraj Med J 2021;73:77-83.
Swain SK, Das S, Kar D, Das SR. Role of computed tomography of the nose and paranasal sinuses in COVID-19 patients with anosmia: Our experiences at a tertiary care teaching hospital. Int J Cur Res Rev 2021;13:117-21.
Prince AD, Stucken EZ. Sudden sensorineural hearing loss: A diagnostic and therapeutic emergency. J Am Board Fam Med 2021;34:216-23.
Swain SK, Acharya S. Bedside tracheostomy on COVID-19 patients in the intensive care unit: A retrospective study. Airway 2021;4:28-34. [Full text]
Long QX, Liu BZ, Deng HJ, Wu GC, Deng K, Chen YK, et al
. Antibody responses to SARS-CoV-2 in patients with COVID-19. Nat Med 2020;26:845-8.
Wu C, Chen X, Cai Y, Xia J, Zhou X, Xu S, et al
. Risk factors associated with acute respiratory distress syndrome and death in patients with coronavirus disease 2019 pneumonia in Wuhan, China. JAMA Intern Med 2020;180:934-43.
Swain SK, Behera IC, Ananda N. Pediatric tracheostomy in COVID-19 pandemic: A review. Int J Contemp Pediatr 2021;8:602-8.
Heilmann S, Huettenbrink KB, Hummel T. Local and systemic administration of corticosteroids in the treatment of olfactory loss. Am J Rhinol 2004;18:29-33.
WHO Rapid Evidence Appraisal for COVID-19 Therapies (REACT) Working Group; Sterne JA, Murthy S, Diaz JV, Slutsky AS, Villar J, et al
. Association between administration of systemic corticosteroids and mortality among critically ill patients with COVID-19: A meta-analysis. JAMA 2020;324:1330-41.
Damm M, Pikart LK, Reimann H, Burkert S, Göktas Ö, Haxel B, et al
. Olfactory training is helpful in postinfectious olfactory loss: A randomized, controlled, multicenter study. Laryngoscope 2014;124:826-31.
Whitcroft KL, Hummel T. Clinical diagnosis and current management strategies for olfactory dysfunction: A review. JAMA Otolaryngol Head Neck Surg 2019;145:846-53.
Swain SK, Das S, Padhy RN. Performing tracheostomy in intensive care unit – A challenge during COVID-19 pandemic. Siriraj Med J 2020;72:436-42.
[Table 1], [Table 2]