Anosmia, a Hidden Sign for COVID-19? A Case Report and Literature Review


 Background The coronavirus disease 2019 (COVID-19) is an ongoing viral pandemic that is actively affecting 210 countries worldwide, with a total of more than 1.5 million cases and 106 000 deaths. Symptoms associated with COVID-19 are mainly fever, cough, dyspnea and sore throat. The current indication for COVID-19 testing includes presence of these symptoms with a positive history of travel to affected countries or contact with COVID-19 patients. Anosmia has been recently reported anecdotally over the past weeks as an emerging symptom of the COVID-19 but has yet to gain recognition as a symptom for COVID-19 by the World Health Organization (WHO) and Centre for Disease Control and Prevention (CDC). This case report highlights a case of isolated sudden onset of anosmia as a presenting symptom of COVID-19 and relevant literature review supporting the incidence of anosmia in COVID-19. This is a first case report of anosmia in COVID-19 occurring in pregnancy.Case Presentation A 30-year-old pregnant lady at 11 weeks of gestation presented with sudden onset of anosmia for one day with no other accompanying symptoms. She had just recovered from a mild cold a day prior to the development of anosmia. She had a history of travel by land to Singapore 14 days prior to onset of anosmia. There was no known close contact with a COVID-19 patient or attended any mass gatherings prior to development of her symptom. She underwent nasopharyngeal and oropharyngeal swab sampling which was then tested using reverse transcription polymerase chain reaction (RT-PCR) method and confirmed infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).Conclusion Clinicians should be aware regarding anosmia as a presenting symptom of COVID-19 especially in the presence of risk factors such as travel to affected countries and having close contact with COVID-19 positive patients. If testing is not done, these patients should be advised for home quarantine to reduce the risk of transmission. Healthcare workers must always adhere to infection control and prevention protocol as well as personal protective equipment.

Background The coronavirus disease 2019  is an ongoing viral pandemic that is actively affecting 210 countries worldwide, with a total of more than 1.5 million cases and 106 000 deaths.
Symptoms associated with COVID-19 are mainly fever, cough, dyspnea and sore throat. The current indication for COVID-19 testing includes presence of these symptoms with a positive history of travel to affected countries or contact with COVID-19 patients. Anosmia has been recently reported anecdotally over the past weeks as an emerging symptom of the COVID- 19 but has yet to gain recognition as a symptom for COVID-19 by the World Health Organization (WHO) and Centre for Disease Control and Prevention (CDC). This case report highlights a case of isolated sudden onset of anosmia as a presenting symptom of COVID-19 and relevant literature review supporting the incidence of anosmia in COVID-19. This is a first case report of anosmia in COVID-19 occurring in pregnancy.

Case Presentation
A 30-year-old pregnant lady at 11 weeks of gestation presented with sudden onset of anosmia for one day with no other accompanying symptoms. She had just recovered from a mild cold a day prior to the development of anosmia. She had a history of travel by land to Singapore 14 days prior to onset of anosmia. There was no known close contact with a COVID-19 patient or attended any mass gatherings prior to development of her symptom. She underwent nasopharyngeal and oropharyngeal swab sampling which was then tested using reverse transcription polymerase chain reaction (RT-PCR) method and confirmed infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).
Conclusion Clinicians should be aware regarding anosmia as a presenting symptom of COVID-19 especially in the presence of risk factors such as travel to affected countries and having close contact with COVID-19 positive patients. If testing is not done, these patients should be advised for home quarantine to reduce the risk of transmission. Healthcare workers must always adhere to infection control and prevention protocol as well as personal protective equipment.

Background
The coronavirus disease 2019 (COVID-19) is an ongoing viral pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and has taken the lives of more than 106 000 people globally (1). The transmission of disease has increased exponentially across many countries within a very brief period. WHO and CDC has recommended that testing for COVID-19 be done for patients who presented with fever, cough, dyspnea or other symptoms compatible to COVID-19 with relevant epidemiological factors under the sound judgement of clinicians (1,2).
Recently, olfactory dysfunction such as hyposmia and anosmia in the absence of other symptoms has been highlighted as an emerging symptom among COVID-19 positive patients and statements have been released by several otorhinolaryngology societies (3,4). This symptom however has yet to be recognized by the WHO or CDC as a symptom of COVID-19. The intent of this case report is to generate awareness among the public and clinicians regarding the possibility of anosmia as a silent marker of COVID-19 and to prompt the international scientific community to consider this clinical manifestation in the current case testing and management guidelines while awaiting more vigorous evidence.
This case report highlights a case of isolated sudden onset of anosmia as a presenting symptom of COVID-19 and relevant literature review supporting the incidence of anosmia in COVID-19. This is a first case report of anosmia in COVID-19 occurring in pregnancy.

Case Presentation
A 30-year-old, gravida 1 lady at 11 weeks of gestation visited the antenatal care clinic at a private hospital for her routine check-up. However, she complained of having sudden onset of anosmia on the day of presentation to the antenatal care clinic. Two days prior, she had fever, mild runny nose and non-productive cough which resolved a day before the development of anosmia. On the day of onset of anosmia, she did not have any fever, cough, runny nose, nasal congestion, shortness of breath, sore throat, vomiting, diarrhea, myalgia, abdominal pain or fatigue. She had no other comorbidities.
She had a history of travel by land in her own vehicle from Johor, Malaysia to Singapore and returned to Johor on the same day 14 days prior to development of anosmia. Her timeline of travel and symptomatology are as in Figure 1. She had no close contact with any known COVID-19 positive patients or attended any mass gatherings prior to development of her symptoms. She lives with her husband who was well.
Upon examination, she was afebrile with normal blood pressure, pulse, respiratory rate and oxygen saturation under room air. She was comfortable and did not appear to be in respiratory distress. Her lung auscultation was clear. She underwent nasopharyngeal and oropharyngeal swab sampling immediately after consultation at the facility which was then tested using reverse transcription polymerase chain reaction (RT-PCR) method. Healthcare workers attending her wore adequate personal protective equipment (PPE) and adhered to infection control protocol.
As per local guidelines, her symptoms did not fulfil the criteria for being a person under investigation (PUI) (5). Thus, she was allowed discharge from the facility with advice for home surveillance.
After approximately 48 hours, her RT-PCR results confirmed the SARS-CoV-2 infection. She was then referred and admitted to the designated COVID-19 hospital for further management. None of the healthcare workers who had contact with her prior to testing developed any COVID-19 symptoms or anosmia up to date. Her husband was tested negative.

Discussion And Conclusion
The current symptoms for suspicion of COVID-19 as outlined by WHO are fever with at least one sign or symptom of respiratory disease such as cough, shortness of breath alongside a history of travel to or residence in a location reporting community transmission of COVID-19 or having been in contact with a confirmed COVID-19 patient or PUI during the 14 days prior to symptom onset (1). The CDC has noted that most persons with COVID-19 will experience fever, fatigue, anorexia, shortness of breath, sputum production and myalgias while less than ten percent of the COVID-19 patients had atypical presentations such as headache, confusion, rhinorrhea, sore throat, haemoptysis, vomiting and diarrhea (2).
Olfactory dysfunctions such as anosmia and hyposmia as a symptom of COVID-19 on the other hand has been anecdotally reported and described by very few studies. It has yet to receive recognition as a symptom to raise suspicion or become a testing indication for COVID-19. The British Rhinological Society, American Academy of Otolaryngology-Head and Neck Surgery and the French Society of Otorhinolaryngology has recently issued expert statements suggesting that anosmia could be a potential feature of COVID-19 (3,4,6). A few studies have been conducted which provides support for the suggestion. The limitations of these studies are mostly due to the state of emergency of the disease, including some not being peer-reviewed, use of unvalidated questionnaires as well as lack of verification of symptoms by clinical examinations. Findings of the relevant studies are as summarized in Table 1.  The cause of anosmia in COVID-19 is yet to be ascertained. Nasal endoscopy still possesses a high risk to doctors during this pandemic and deferment of the procedure has been recommended. It has been hypothesized that anosmia could be due to an insult occurring at the neuro epithelium of the olfactory receptor cells in the nasal roof or central olfactory routes (7,15). A study investigating human and mouse data sets found that olfactory epithelial support cells, stem cells and nasal respiratory epithelium cells expresses the two key genes, angiotensin converting enzyme 2 (ACE2) and transmembrane serine protease 2 (TMPRSS2) which enables proteins production. These proteins then enable the attachment of SARS-CoV-2 onto cells (15). This discovery evokes a probable mechanism of anosmia in COVID-19 and warrants further research for validation.
In relation to our case, the symptoms of COVID-19 in pregnancy has been reported to be similar with the non-pregnant adults which are fever, sore throat, malaise, dyspnea and cough (16). The COVID-19 severity is also equivalent to the non-pregnant population with the majority cases being mild (17).
There are currently no data suggesting an increased risk of miscarriage or early pregnancy loss however, those who develop pneumonia were found to have a higher incidence of preterm labour, preterm birth, prelabour rupture of membranes, pre-eclampsia and caesarean delivery for abnormal fetal heart tracings (18). Vertical transmission of COVID-19 is yet to be established but studies have shown that samples of amniotic fluid, cord blood, breastmilk and neonatal throat swabs were negative for SAR-CoV-2 (19). As of time of this writing, there are no reported cases of maternal death due to COVID-19.
The patient in our case has been allowed discharge from the COVID-19 designated hospital after her repeated RT PCR after 72 hours was negative. She did not develop any respiratory distress or experienced any signs of miscarriage or pregnancy loss. She has been advised for home quarantine for 14 days. She was pleased that the attending physician who first saw her was aware of anosmia being a probable symptom of COVID-19 and tested her despite not fulfilling the criteria for testing (5).
She is thankful that COVID-19 was promptly detected, and she was referred for further management by a multidisciplinary team.

Consent for publication
Written informed consent was obtained from the patient for publication of this case report. A copy of the written consent is available for review by the Editor-in-Chief of this journal upon request.

Availability of data and materials
Data will be made available upon reasonable request. Figure 1 Patient's timeline from history of travel to development of anosmia

Supplementary Files
This is a list of supplementary files associated with this preprint. Click to download. Table1BMCanosmia.docx Table2BMC.docx