What is the evidence for anosmia (loss of smell) as a clinical feature of COVID-19?
March 23, 2020
James O’Donovan, Sarah Tanveer, Nicholas Jones, Claire Hopkins, Brent A. Senior, Sarah K. Wise, Jon Brassey, Trisha Greenhalgh
On behalf of the Oxford COVID-19 Evidence Service Team
Centre for Evidence-Based Medicine, Nuffield Department of Primary Care Health Sciences
University of Oxford
Department of Education
University of Oxford
Correspondence to firstname.lastname@example.org
Lay Summary by Mandy Payne, Health Watch
Sniffing out the evidence for olfactory symptoms as a clinical feature of COVID-19: A Systematic Scoping Review
The current evidence base to suggest changes in olfactory sensation is a feature of COVID-19 is limited and inconclusive. More evidence is required to establish whether there is a link between changes in olfaction and COVID-19; we therefore encourage clinicians to incorporate questions around loss of olfactory sensation into their clinical practice when assessing patients with suspected COVID-19.
There are two types of change in olfactory sensation – anosmia and hyposmia:
What is anosmia?
Anosmia is a total loss of the sensation of smell.
What is hyposmia?
Hyposmia is the partial loss of the sensation of smell.
Why do this review now?
Dozens of recent media reports have suggested new-onset anosmia in the absence of nasal obstruction or underlying respiratory disease may be a clinical feature of COVID-19.1-3
What was the objective of the review?
To understand the existing evidence surrounding olfactory symptoms (anosmia and hyposmia) as a clinical feature of COVID-19.
What data sources did we use?
We conducted a rapid systematic scoping review of the literature and searched 5 major databases (Medline; Embase; via Ovid; CINAHL via Ebsco; Web of Science and Scopus; via ProQuest).
We also searched the grey literature (member websites of The International Federation of Otorhinolaryngology (ORL) Societies (IFOS),https://www.medrxiv.org/ (a pre-print server for unpublished manuscripts in the field of health-sciences); and websites of relevant professional bodies (e.g. Society of Sensory Professionals, Fifth Sense UK) and combined this with expert consultation.
What were criteria for inclusion?
Studies or evidence published between the 31st of December 2019 and the 23rd of March 2020 was eligible for inclusion. No restrictions were placed on language. Studies were eligible for final inclusion if they described clinical features of COVID-19– specifically those related to olfactory symptomatology.
How did we grade evidence?
Included evidence was graded using the Oxford Centre for Evidence-based Medicine (CEBM) Levels of Evidence guideline.
What is the evidence behind the suggestion that changes in olfaction could be a feature of COVID-19?
We identified four relevant pieces of evidence suggesting that olfactory symptoms could be a potential clinical feature of COVID-19. These included:
- A non-peer reviewed study by Mao et al., from China where 11 of 214 (5.1%) patients with confirmed SARS-CoV-2 complained of hyposmia; however this finding was not deemed significant (p=0.338).4
- Three expert statements from the American, British and French associations of otorhinolaryngology.5-7
It is important to note that the statements from the professional bodies are largely based on anecdotal non-peer reviewed emerging clinical observations. The ENT UK statement (which has so far received the most traction in the popular media) stated that they had “good evidence” from multiple countries that patients with confirmed COVID-19 had also developed olfactory symptoms.
After clarifying this information with an ENT UK representative we now know that this was largely based on anecdotal messages shared amongst clinicians on a private online forum for otolaryngologists. Due to privacy regulations we were unable to gain access to the group to analyse the message exchanges.
The press release also stated that “in South Korea, where testing has been more widespread, 30% of patients testing positive have had anosmia as their major presenting symptom in otherwise mild cases”.6 This evidence refers to a media report by a Korean news outlet. A journalist interviewed doctors at hospitals in Daegu. One doctor was quoted as saying: “If you put together the doctors who conducted ward rounds or spoke to patients on the phone, approximately 30% of the confirmed (COVID-19 positive) patients reported a loss of smell as a symptom”.8
What is the strength of the evidence to suggest olfactory symptoms are a potential clinical feature of COVID-19?
Overall the evidence was graded as ‘inconclusive’ (Grade D) using the CEBM guideline.
Through the systematic-review process we also identified 56 peer-reviewed studies which described clinical features in confirmed cases of COVID-19. None of these studies mention olfactory symptoms as a clinical feature of COVID-19.
EMERGING EVIDENCE IN COVID-19
- The current state of evidence around changes in olfactory sensation being a clinical feature is highly preliminary and largely based around non peer-reviewed emerging anecdotal clinical information.
- Changes in olfaction, secondary to COVID-19, have not been mentioned as a symptom in any of the existing 56 peer-reviewed studies where symptoms of patients with confirmed cases of disease have been reported.
- This could be for several reasons: (i) symptoms around olfaction may not have been elicited and recorded (ii) unless patients are consciously monitoring for olfactory loss, many of them may not become aware of this manifestation or seek medical attention for days to weeks (iii) olfactory loss might be a symptom in milder cases of disease, rather than critically ill patients who required hospitalisation (which has formed that vast majority of patients included in the peer-reviewed literature to date).
- The preliminary current evidence base for olfactory symptoms as a potential feature of COVID-19 is limited to expert statements and one non-peer reviewed paper and inconclusive at this time. However, emerging anecdotal clinical reports suggest that this feature should be investigated further. Any new onset anosmia, in the absence of nasal obstruction or respiratory symptoms, should be recorded by clinicians who suspect a patient may be positive for COVID-19.
Disclaimer: the article has not been peer-reviewed; it should not replace individual clinical judgement and the sources cited should be checked. The views expressed in this commentary represent the views of the authors and not necessarily those of the host institution, the NHS, the NIHR, or the Department of Health and Social Care. The views are not a substitute for professional medical advice.
James O’Donovan is a DPhil candidate and medical doctor at the Department of Education, University of Oxford. Twitter: @james_odonovan
Sarah Tanveer is a PhD candidate at The University of Maryland. Twitter: @SarahTanveer_
Nicholas Jones is a Wellcome Trust Doctoral Research Fellow at University of Oxford.
Claire Hopkins is Professor of Rhinology, Kings College London, UK.
Brent A. Senior is Professor of Otolaryngology/Neurosurgery at UNC School of Medicine, USA.
Sarah K. Wise is Professor Rhinology/Sinus Surgery at Emory Medicine, USA.
Jon Brassey is the Director of Trip Database Ltd, Lead for Knowledge Mobilisation at Public Health Wales (NHS) and an Associate Editor at the BMJ Evidence-Based Medicine
Trisha Greenhalgh is Professor of Primary Care at the University of Oxford. Twitter: @trishgreenhalgh
The following combination of search terms were used to search the literature:
- “SARS‐CoV‐2” OR “2019‐nCoV” OR “Coronavirus” OR “COVID-19”
- “Anosmia” OR “Hyposmia” OR “loss of smell” OR “symptom*” OR “clinical feature*” OR “Smell” OR “olfact*”
- CNN. Doctors say loss of sense of smell might be Covid-19 symptom. 2020; https://edition.cnn.com/2020/03/23/health/coronavirus-symptoms-smell-intl/index.html. Accessed 23/03/2020.
- Roni Caryn Rabin. Lost Sense of Smell May Be Peculiar Clue to Coronavirus Infection. New York Times. 23rd March 2020, 2020.
- The Independant. Coronavirus: New symptom of virus could be loss of taste and smell, top UK doctor says. 2020; https://www.independent.co.uk/news/health/coronavirus-symptoms-taste-smell-loss-ear-nose-throat-a9416226.html. Accessed 23/03/2020.
- Mao L, Wang M, Chen S, et al. Neurological Manifestations of Hospitalized Patients with COVID-19 in Wuhan, China: a retrospective case series study. 2020.
- American Academy of Otolaryngology – Head and Neck Surgery. AAO-HNS: Anosmia, Hyposmia, and Dysgeusia Symptoms of Coronavirus Disease. 2020; https://www.entnet.org/content/aao-hns-anosmia-hyposmia-and-dysgeusia-symptoms-coronavirus-disease. Accessed 23/03/2020.
- ENT-UK. Loss of sense of smell as marker of COVID-19 infection 2020; 2. Available at: https://www.entuk.org/sites/default/files/files/Loss%20of%20sense%20of%20smell%20as%20marker%20of%20COVID.pdf.
- Alerte Anosmie COVID-19 [press release]. France, 20/03/2020 2020.
- ChoSun. [최보식이 만난 사람] “가장 힘들고 위험한 일 시켜달라… 이름 노출은 원치 않던 그 의사들 출처 2020; https://news.chosun.com/site/data/html_dir/2020/03/16/2020031600009.html. Accessed 22/03/2020.