Loss of smell is the best predictor of COVID-19

A large international team of researchers has conducted a crowdsourced cross-sectional study, in which they have investigated the reliability of the olfactory loss (or loss of smell, or anosmia) as a predictor of coronavirus disease 19 (COVID-19).

Both COVID-19 positive (C19+) and COVID-19 negative (C19-) groups suffering from respiratory symptoms exhibited loss of smell. However, the loss was significantly greater in C19+ individuals.

The study, published in the journal Chemical Senses, found that recent loss of smell is the best predictor of COVID-19 amongst individuals with respiratory illness, and they recommend a novel 1-10 scale, Olfactory Determination Rating scale for COVID-19, dubbed ODoR-19, to screen individuals with recent olfactory loss.

Study: Recent Smell Loss Is the Best Predictor of COVID-19 Among Individuals With Recent Respiratory Symptoms. Image Credit: Nenad Cavoski/ Shutterstock​​​​​​​

Study: Recent Smell Loss Is the Best Predictor of COVID-19 Among Individuals With Recent Respiratory Symptoms. Image Credit: Nenad Cavoski/ Shutterstock

Background

Loss of smell, taste, and chemesthesis can have severe consequences associated with quality of life for patients. However, their role in diagnosing COVID-19 is still underappreciated due to a general lack of awareness regarding anosmia and other chemosensory disorders by clinicians and the public, including their potential association with respiratory infections.

According to previous reports, sudden loss of smell and taste are key early and specific signs of COVID-19 illness, which are exhibited distinctively in otherwise asymptomatic individuals. Yet little research has been conducted on the impact, duration, and reversibility of smell loss caused by COVID-19. In order to identify the chemosensory dysfunctions associated with COVID-19 and determine their relevance as predictors of this disease, the researchers conducted the current study.

What did the researchers do?

Crowdsourced survey data (19 April 2020 to 3 July 2020) were collected from the Global Consortium for Chemosensory Research (GCCR) core questionnaire that was deployed in 23 languages across the globe via social media, traditional media as well as the GCCR website.

The survey aimed to determine if changes in chemosensory functions distinguish individuals with COVID-19 from those with other respiratory infections.

Binary (Yes/No) responses, definite questions, and visual analog scales (VAS) were used to measure self-reported chemosensory ability, along with other symptoms and characteristics, of COVID-19-positive (C19+) and COVID-19-negative (C19−) individuals with recent or current symptoms of respiratory sickness.

The entry criterion for participation in the survey was the occurrence of a recent or current respiratory illness. On this basis, a total of 15,747 participants were included in the present analyses.

Based on responses to Question: “Have you been diagnosed with COVID-19?”-participants were assigned to either of the following groups.

  • C19+ Lab-tested group (C19+): included participants that were diagnosed with COVID-19 in a lab test
  • C19- Lab-tested group (C19-): were negative in a COVID-19 lab test but had similar respiratory symptoms.
  • C19+ Clinical group: were diagnosed COVID-19 positive based on symptoms only.
  • C19 Unknown group: were not diagnosed by any test but had symptoms.

The team also conducted analysis on the matched population sizes of C19+ and C19- subjects (n = 546 each) with matched age and gender distributions.

Logistic regression models identified univariate and multivariate predictors of COVID-19 status and post-COVID-19 olfactory recovery.

Smell, taste, and chemesthesis abilities drop significantly in COVID-19 patients

Both C19+ Lab-tested group and C19+ Clinical group exhibited significant chemosensory losses.

The team then compared chemosensory abilities and nasal blockage in lab-tested C19+ and C19- participants. C19+ participants reported greater loss of smell (C19+: −82.5 + 27.2 points vs C19−: −59.8 + 37.7 points; P = 1.1 × 10-59); taste (C19+: −71.6 + 31.8 points vs C19−: −55.2 + 37.5 points; P = 7 × 10-24,); and chemesthesis ability (C19+: −36.8 + 37.1 points; C19−: −28.7 + 37.1 points; P = 4.6 × 10-5).

Smell loss is more predictive of COVID-19 than other cardinal signs such as fever and sore throat

The quality of each model was measured using the receiver operating characteristic (ROC) area under the curve (AUC). The team observed that self-reported smell loss during illness, reported on a continuous scale, was the most predictive survey question for COVID-19 status (AUC = 0.71).

Also, alterations in smelling ability during and before COVID-19 illness were similarly predictive (AUC = 0.69). Changes in taste ability were the next most predictive variables (AUC = 0.64–0.65).

The most well-known non-chemosensory symptom, sore throat, was considerably less predictive (AUC = 0.58) than the chemosensory symptoms. Nasal obstruction was not at all predictive (AUC = 0.52).

Responses given on a continuous scale were found to be more predictive than binary Yes/No responses to parallel questions, probably because a continuous scale contains a more significant amount of diagnostic information. Therefore using ‘Days since Onset of Respiratory Symptoms (DOS)’, which was measured relative to the survey completion date, proved to be a better predictor (AUC = 0.72, +0.01 vs. the Smell Only model) when compared to ‘Smell during illness (Smell Only)’

Recovery from chemosensory losses

Overall, the self-reported, post-illness olfactory ability was lower for C19+ group. A similar but smaller effect of COVID-19 status on recovery was observed for taste, whereas little to no association with COVID-19 was observed for recovery of chemesthesis or nasal obstruction. Olfactory recovery within 40 days of respiratory symptom onset was reported for ~50% of participants and was best predicted by days since respiratory symptom onset (DOS). Quantified smell loss was found to be the best predictor of COVID-19 amongst those with symptoms of respiratory illness.

ODoR-19, an anosmia-based screening for COVID-19

To assess an individual’s COVID-19 risk quickly and reliably, the SARS-CoV-2 pandemic requires healthcare providers and contact tracers. Thus, reliable screening tools are critical to evaluate a person’s likelihood of having COVID-19 and to implement self-quarantine or other testing recommendations. Some reports have even suggested that COVID-19-associated smell loss might indicate disease severity. However, current cardinal symptoms such as fever, dry cough are less specific than severe smell loss in distinguishing between COVID-19 and other respiratory illnesses.

The team thus proposes a quick, simple-to-use, telemedicine-friendly tool, the ODoR-19, a 0–10 numeric rating scale to improve the utility of current COVID- 19 screening protocols, particularly when access to rapid testing for SARS-CoV-2 is limited. Thus, ODoR-19 can precede and complement viral testing in remote conditions when the pandemic conditions are severe. The study found that responses to the ODoR-19 scale ≤2 indicated high odds of COVID-19 positivity (4 < OR < 10).

“Those who receive a negative outcome from a COVID-19 viral test, yet report significant idiopathic smell loss, should be considered as high-priority candidates for COVID-19 re-testing and self-isolation”, advises the team.

Journal reference:
Namita Mitra

Written by

Namita Mitra

After earning a bachelor’s degree in Veterinary Sciences and Animal Health  (BVSc) in 2013, Namita went on to pursue a Master of Veterinary Microbiology from GADVASU, India. Her Master’s research on the molecular and histopathological diagnosis of avian oncogenic viruses in poultry brought her two national awards. In 2013, she was conferred a doctoral degree in Animal Biotechnology that concluded with her research findings on expression profiling of apoptosis-associated genes in canine mammary tumors. Right after her graduation, Namita worked as Assistant Professor of Animal Biotechnology and taught the courses of Animal Cell Culture, Animal Genetic Engineering, and Molecular Immunology.

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