INTRODUCTION
While initial reports did not highlight such symptoms, recent data from several countries
suggest that SARS-CoV-2-positive inpatients experienced loss of smell and/or taste.
1, 2
In a retrospective web-based study of outpatients who had attended one of three emerging
diseases center in France, the combination of hyposmia and hypogeusia had moderate
sensitivity (42%) and high specificity (95%) for the identification of SARS-CoV-2-positive
patients.
2
While loss of smell or taste could be a key symptom to guide early identification
of new cases in primary care, the extent to which participants in this study were
representative of primary care patients is unclear. To address this limitation, we
conducted a study involving primary care patients in France.
METHODS
This preliminary cross-sectional study was conducted between March 24, 2020, and April
14, 2020, in two clinical laboratories in Lyon (France) to which general practitioners
(GPs) refer patients with a suspicion of COVID-19 for a nasopharyngeal smear (RT-PCR).
Before undergoing the test, the patients responded to a pre-formatted questionnaire
about their symptoms, built on previous literature
3, 4
and expert opinion. Data were analyzed using Stata 15, adjusting for clustering within
the two laboratories. We examined the univariate and multivariate association between
smell and/or taste disorders and a positive SARS-CoV-2 test, adjusting for all the
other symptoms frequently reported by the patients. We also examined the performance
of these smell and taste symptoms in predicting a SARS-CoV-2-positive test.
RESULTS
A total of 816 consecutively recruited patients were included in the analysis; 532
(65%) were women. The median age was 45 (interquartile range, 28; min–max, 4–92);
302 (37%) were healthcare professionals. Cough and dry throat were the most frequently
reported symptoms (Table 1). Patients who tested positive for SARS-CoV-2 (n = 198
(24%)) reported loss of smell or taste significantly more often than patients who
tested negative (Table 2). Smell or taste disorders were significantly associated
with positive RT-PCR with an adjusted OR = 6.3 (95% CI, 5.2–7.5) in this primary care
population with a high pre-test probability of COVID-19.
Table 1
Proportion of Symptoms Reported by Patients (N = 816)
Symptoms
N (%)
Anosmia or hyposmia
156 (19.1)
Ageusia or hypogeusia
188 (23.0)
Fever*
366 (44.9)
Asthenia
115 (14.1)
Headache*
359 (44.1)
Cough
450 (55.2)
Dyspnea
143 (17.5)
Chest pain*
164 (20.1)
Myalgia
166 (20.3)
Diarrhea*
174 (21.4)
Dry nose*
173 (21.2)
Stuffy nose*
211 (25.9)
Dry throat*
384 (47.1)
Sore throat
54 (6.6)
*Data missing for 1 patient
Table 2
Association Between Smell and/or Taste Disorders, and Positivity of the SARS-CoV-2
RT-PCR Test
Symptoms
Overall (N = 816), n (%)
Patients with a positive test (N = 198), n (%)
Patients with a negative test (N = 618), n (%)
Crude OR (95% CI)1
p value1
Adjusted OR (95% CI)2
Adjusted p value2
Sensitivity (%)
Specificity (%)
ROC area (95% CI)
Smell disorder 3
156 (19.1)
82 (41.4)
74 (12.0)
5.2 (4.3-6.3)
< 0.001
6.3 (5.8–6.9)
< 0.001
41.4
88.0
0.65 (0.61–0.68)
Taste disorder 4
188 (23.0)
92 (46.5)
96 (15.5)
4.7 (3.4–6.6)
< 0.001
4.9 (3.2–7.5)
< 0.001
46.5
84.5
0.66 (0.62–0.69)
Smell and taste disorder3,4
102 (12.5)
58 (29.3)
44 (7.1)
5.4 (2.9–10.1)
< 0.001
5.9 (3.2–11.1)
< 0.001
29.3
92.9
0.61 (0.58–0.64)
Smell or taste disorder3,4
242 (29.7)
116 (58.6)
126 (20.4)
5.5 (4.6–6.7)
< 0.001
6.3 (5.2–7.5)
< 0.001
58.6
79.6
0.69 (0.65–0.73)
1Univariate logistic regression (adjusted for clustering within labs)
2Multivariate logistic regression (adjusted for clustering within labs, gender, age
group, and patient reporting of fever, asthenia, headache, cough, dyspnea, chest pain,
myalgia, diarrhea, dry nose, stuffy nose, dry throat, sore throat)
3Anosmia or hyposmia
4Ageusia or hypogeusia
DISCUSSION
The tropism of SARS-CoV-2 for the nerves of the ear, nose, and throat system
5
may explain the relatively high proportion of SARS-CoV-2 patients suffering from smell
and taste disorders, compared with patients suffering from upper respiratory tract
infections with other viruses.
In this epidemic context, a simple clinical screening tool could be very efficient.
Smell and taste disorders seem to be very specific to SARS-CoV-2 infection. This is
a key finding to inform triage strategies and early isolation of new clusters of infection
through primary care. The high specificity of these symptoms means GPs could rely
on them to affirm a diagnosis of COVID-19, referring only patients with low pre-test
probability (i.e., with non-specific symptoms) to RT-PCR screening. This could be
a strategy to consider in lower resource settings, when RT-PCR testing is not widely
available, or lack of protective gear would lead to excessive risk of contamination
for the caregiver performing the test.
Our study was initiated after the first media reports of a possible link between anosmia
and COVID-19. This may have prompted patients to over-report these symptoms, thus
affecting their prevalence in our sample. Since patients were asked about the symptoms
before receiving the results of their test, this limits the repercussions of this
potential reporting bias on our measures of association.
Future studies should explore the diagnostic performance of various combinations of
symptoms (i.e., anosmia and ageusia, anosmia without rhinitis, anosmia with nasal
dryness…) to increase the specificity of the clinical picture. In accordance with
Wynants et al.’s recommendations,
6
these studies should be performed with a representative dataset (i.e., primary care–based
sample), an adequate description of the study population and external validation of
the diagnostic tool.
In conclusion, our study shows that smell and taste disorders are common in primary
care patients with SARS-CoV-2 infection. These symptoms might represent the first
step to build a relatively simple clinical screening tool to use in primary care in
an epidemic context. Once confinement measures are lifted, our data could further
inform triage and early identification of new clusters of cases through primary care.