Smell Rehabilitation in Prolonged Anosmia in a COVID-19 Patient

Case Report Paulina Maria Angela C. Villar, MD-MBA*, Ryan Chua, MD, Ruby P. Robles, MD

The Medical City, Ortigas Avenue, Pasig City *pmacvcillar@gmail.com

ABSTRACT: During the height of the COVID-19 pandemic, anosmia was recognized as one of the symptoms of this disease. The majority of the cases in Europe described it as sudden acute olfactory dysfunction without nasal congestion/obstruction or rhinorrhea with complete resolution after a few weeks. However, a small percentage would take longer to recover while some do not recover completely. In this case, a 41-year-old previously healthy female who presented with mild symptoms developed anosmia, phantosmia, and parosmia during the course of her disease. Olfactory bulb atrophy was also noted on Cranial and Paranasal MRI. Due to its prolonged duration, smell rehabilitation was initiated as treatment. Although smell rehabilitation or olfactory training has been recommended for those with anosmia, there are so far no published documentation of its benefit in COVID-19 anosmia. This case report aims to contribute to existing data by presenting a full documentation of a confirmed COVID-19 patient that presented with anosmia, beginning from presentation up until treatment. It aims to provide awareness of how differently anosmia can present as compared to those seen in published studies. Finally, this case report also shows how olfactory training can contribute to treatment of patients with prolonged anosmia. Keywords: Anosmia; COVID-19; Olfactory Bulb Atrophy; Olfactory Training; Smell Rehabilitation INTRODUCTION Viruses are well known to cause olfactory dysfunction, a condition called post-infectious olfactory dysfunction (PIOD). Patients with this condition often continue to experience impaired smelling capabilities despite the resolution of other symptoms. As early as 2007, studies have shown that the common viruses such as rhinovirus, coronavirus, parainfluenza virus, and ebstein bar virus were isolated in the nasal discharge of patients with PIOD1. At the start of this year, a new highly contagious coronavirus was discovered that causes severe acute respiratory syndrome. This eventually led to the now ongoing pandemic called COVID-19. Around March 2020, during the height of the pandemic, anosmia was recognized as one of its symptoms. The majority of the cases in Europe described it as sudden olfactory dysfunction without nasal congestion/obstruction or rhinorrhea. In a study by Lechien et al., wherein they studied 357 COVID-19 patients, 85% had olfactory dysfunction, 79.6% were anosmic while 20.4% were hyposmic. Phantosmia and parosmia were experienced later in the course of the disease2. They also noted that olfactory symptoms preceded the more recognized COVID-19 symptoms such as fever, cough, myalgia, loss of appetite, diarrhea, and headache, which often led to a delay in the diagnosis of COVID 19. This pointed out the importance of anosmia as part of the symptamotology of the disease. Their study also observed that after most ENT symptoms had resolved, olfactory dysfunction persisted in 63% of the cases, which became a concern to the quality of life of these patients1. Recent studies have also shown that anosmia in COVID-19 was acute rather than a permanent complication. According to Lechien et al, patients recovered their olfactory function within the first 8 days following resolution of the disease. Meanwhile, a study done in Korea3 stated that most patients recovered within 21 days. This case report aims to contribute to existing data by presenting a full documentation of a confirmed COVID-19 patient that presented with anosmia, beginning from presentation up until treatment. It aims to provide awareness of how differently anosmia can present as compared to those seen in published studies. Finally, this case report also shows how olfactory training can contribute to treatment of patients with 1

prolonged anosmia, a therapy widely used in western countries but has not been documented in a COVID- 19 case. CASE This is a case of a 41-year-old female who presented with anosmia at the height of the COVID-19 pandemic in the Philippines. She had no known exposure to a confirmed COVID-19 case, no recent travel history, and no complaints regarding her sense of smell prior to this year. She came from maternity leave and returned to work on March 2, 2020. After one week (March 9, 2020), the patient initially complained of sore throat and nasal congestion which she attributed to her allergic rhinitis. On day nine (March 17, 2020), the patient developed post nasal drip which she treated with her usual allergy medication - fluticasone furoate nasal spray (Avamys) and loratadine. In the interim, the patient started to develop a severe persistent frontal headache and a non-productive cough. Thirteen days after the patient developed her first symptom (March 21, 2020), she lost her sense of smell and taste. The patient then developed pain on her left maxillary area which prompted her to seek teleconsultation with a general practitioner. She was prescribed with prednisone 20mg/tab taken twice a day for three days, and then thrice a day for three more days, cefuroxime 500mg/tab, taken one tab twice a day for five days, and salbutamol nebulization. All of the patient’s symptoms resolved except for her anosmia. Two months after her first symptom (week of June 1 to 6), the patient developed phantosmia. She was able to smell smoke despite no evidence of smoke in the area. On June 4, 2020, she sought consult with an ENT. Given that all her other COVID-19 symptoms had already resolved, she was no longer a candidate for reverse transciptase polymerase chain reaction (RT PCR) assay based on the Philippines’ protocols. A nasal endoscopy was done which showed unremarkable results. A paranasal MRI was requested. At this time, the patient was also referred to a neurologist and a cranial MRI was done to investigate any neurological causes of anosmia. Both the paranasal MRI and cranial MRI showed symmetrical atrophy of the olfactory bulbs (Figure 1). On smell testing, using the University of Pennsylvania Smell Identification Test (UPSIT), the patient scored 22/40, which corresponded to severe microsmia. The patient was then referred to a rhinologist and was prescribed with oral steroids, omega 3, and fluticasone furoate. On the third week of June, the patient started smell rehabilitation, which consisted of inhaling 4 scents. These were clove, Ylang-ylang, lemon, and eucalyptus inhaled twenty seconds twice a day, once before breakfast and once before bedtime. A smell journal was also asked of the patient to record what scents she can smell around her household and to monitor her progress daily. Before the start of the week, online consultations with the rhinologist were done to document and assess improvement in terms of smell identification, discrimination, and threshold. Three months after the first symptom (July 10, 2020), the patient took the SARS COV 2 electrochemiluminiscence immunoassay (ECLIA) antibody test, which showed presence of COVID-19 IgG antibodies corresponding to either the recovery or convalescence phase. At this time, the patient was already hyposmic with the ability to smell some scents, though still with some distortion. Currently, the patient is on her 4th month of smell rehabilitation. Aside from her allergic rhinitis, the patient also had a history of mild epilepsy eighteen years prior with no recurrence since and with no ongoing maintenance medications. A normal electroencephalography (EEG) also confirmed no recurrence of the seizure. The patient previously smoked one stick of cigarette per week for four years and stopped one year prior. DISCUSSION In this case, we described a patient who seemingly started out with symptoms attributed to allergic rhinitis that eventually was considered as anosmia secondary to COVID-19 infection. Unlike most cases reported in the literature, the patient did not undergo RT PCR testing since at the time that she sought consult, she 2

was already asymptomatic and past fourteen days from symptom onset. According to the Centers for Disease Control and Prevention (CDC)4, viral RT PCR testing is used to diagnose current infections. On the other hand, antibody testing can be done to determine past COVID-19 cases since antibodies only develop one to three weeks after infection5 and are useful mostly for sero-epidemiological surveys and research. With this case, the patient took an ECLIA antibody test three months since her presumed onset of symptoms. According to Tan-Lim et al, the ECLIA test has an 82.4% sensitivity if used at least fourteen days from onset of symptoms; anytime earlier gives a lower sensitivity. This patient presented first with nasal congestion which resolved prior to the onset of her anosmia. However, she experienced frontal headache and maxillary pain concomitant with her loss of sense of smell. As mentioned earlier, anosmia in COVID 19 usually presents suddenly without nasal congestion or evidence of nasopharyngeal abnormalities, but this does not mean that it exclusively occurs without other ear, nose, throat symptoms. In a study by Klopfenstein et al. describing the features of anosmia in COVID- 19, they noted cases where 57% presented with rhinorrhea and 30% had nasal obstruction6. In the same study, 84% of the cases also experienced headache along with other symptoms of fatigue, myalgia, fever, and cough. For this particular patient, a paranasal MRI and Cranial MRI showed symmetric atrophy of the olfactory bulb. In the paranasal MRI, the right olfactory bulb measured 0.8mm while the left measured 1.1mm, both of which were smaller than the normal measurements of 2.1-2.3mm7. Most studies that have documented COVID-19 anosmia with supporting MRI studies showed normal olfactory bulbs. However, in a study done by Chiu et al. of a 19-year-old RT PCR confirmed case of COVID-19, evidence of olfactory bulb atrophywas found, compared to the patient’s pre-COVID MRI images which were within normal limits8. The exact mechanism of olfactory loss in COVID-19 is still debatable. However, it is well established that some viruses can damage the olfactory neuroepithelium. Further studies are needed to analyze olfactory bulb atrophy to determine its exact mechanism. In terms of olfactory loss, studies in Europe leaned towards the explanation that it is caused by viral entry, infection, and death of sustentacular cells but does not necessarily lead to infection, damage, death, and the need for regeneration of olfactory receptor neurons as most of their cases involved isolated acute onset anosmia9. In Asia however, documented cases show longer durations lasting around three weeks and are mostly with other nasal symptoms. According to Butowt et al., regardless if it is due to underreporting or to mutations or genetic variability of the virus and host, there seems to be a difference between the presentation of anosmia in western and Asian cultures. The UPSIT is a well-validated 40-odorant test that objectively measures the sense of smell of a patient and can be used as a biomarker for COVID-19 especially for patients who have mild to moderate symptoms10. With this patient, her UPSIT was done both to objectively assess smell function and as a baseline in monitoring her progress after smell rehabilitation. New onset anosmia in COVID-19 is a fairly new condition and protocols for management has not yet been established in the country. However, as early as May 19 of this year recommendations for management were published in the ENTUK website. Included in this is an algorithm (figure 2) which recommended olfactory training for patients with anosmia that persisted for more than two weeks. Olfactory training has been known to improve olfactory sensitivity through structured, short term exposure to odors11. Anosmia cases are advised smell training by being exposed to four odorants twice a day over three months, and then another four odorants in the next three months12. This is a therapy to enhance or amplify olfactory recovery well studied by Hummel et al. with the speculation that this method improves odor thresholds and, by implication, the architecture of the peripheral olfactory system, and that olfactory training changes the processing of olfactory information. Given that most documented cases of COVID 19 anosmia recover completely, studies regarding olfactory training in COVID-19 is largely unavailable. This makes the documentation of this patient’s therapy with smell training even more valuable, as it may serve as a reference for other COVID-19 patients that also experience a prolonged course of anosmia that does not resolve spontaneously. AbScent13, a UK based organization dedicated to raising awareness of anosmia, provided online instructional materials on how to conduct smell training at home based on the therapy designed by Hummel et al. This has become helpful to those unable to seek professional consult due to the pandemic. With this patient, she is currently on her fourth month of smell rehabilitation. As mentioned earlier, aside from performing smell training daily, the patient also has a smell journal which aids in not just 3

documenting her progress or the extent of smell distortion, but also providing psychological insight to those with prolonged course of parosmia as improvements may seem too subtle for these patients to recognize13. Given the high expense of diagnostic tests in our country which many patients are not able to afford, full documentation of anosmia in COVID-19 cases is scarce. Although anosmia is not considered a severe symptom of this disease, it is often very noticeable and may cause a diminished quality of life for patients. Therefore, cases such as this should be recorded to add to the current information we have on this topic in order to further develop effective management that may help improve their quality of life. ACKNOWLEDGEMENT The authors would like to thank our case patient who voluntarily accepted to share her condition and experience for the purpose of this case report. REFERENCES

1. [1] Suzuki M, Saito K, Min WP, et al. Identification of viruses in patients with postviral olfactory dysfunction. Laryngoscope. 2007;117(2):272-277

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3. [3] Lee Y, Min P, Lee S, Kim S. Prevalence and Duration of Acute Loss of Smell or Taste in COVID- 19 Patients. J Korean Med Sci. 2020;35(18). doi:10.3346/jkms.2020.35.e174

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5. [5] Tan-Lim C, Burog A. Should electrochemiluminescence immunoassay (ECLIA) tests be used in the diagnosis of COVID-19?. Psmid.org. https://www.psmid.org/wp- content/uploads/2020/08/ECLIA-20200823_180625.pdf. Published 2020. Accessed September 19, 2020.

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13. [13] AbScent. Abscent.org. https://abscent.org/. Published 2020. Accessed September 30, 2020.

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LIST OF FIGURES Figure 1. MRI of the of the olfactory bulb using T2 weighted CISS sequence, coronal slice. There is symmetrical flattening of the olfactory bulb as shown by the arrow. Figure 2. Management Algorithm. Recommendations provided by ENTUK.org 5