Our study sample consisted of 1543 primary care patients tested in two laboratories in the Lyon area (France), with 16% positive tests for SARS-CoV-2. We found that dry nose, loss of taste and/or smell and muscle pain were more frequent in patients with a positive test, while sore throat, stuffy nose, dyspnea and diarrhea were more frequent in patients with a negative result. We also found that the two symptoms most strongly associated with a positive test were loss of taste and smell, and that the combination of these two symptoms resulted in an even stronger association. The odds of having a positive test were more than six times greater than the odds of having a negative test if patients had loss of taste and/or smell.
Strengths and limitations
Several limitations must be kept in mind when considering the results. The study took place in a single French region (Greater Lyon). Our results are therefore not necessarily generalizable to other regions in France or to other countries. Due to the heavy workload in the SARS-CoV-2 screening laboratories, we did not ask the healthcare professionals receiving the patients to report the characteristics of those who refused to participate. We do not know if these 18 patients had different clinical presentations than those who agreed to participate. For the same reason (time constraint), we have only limited data on the socio-demographic characteristics of the participants. In particular, we do not have information on their socio-economic level. We had a few dozen missing data for some important variables. However, if we carried out the bi- and multivariate comparison analyses after assigning the subgroup mean (conditional mean) to the missing data, the differences observed between the two groups of patients (patients with positive and negative tests) remained statistically significant. Finally, our results are also limited by the diagnostic performance of the nasal swabs for RT-PCR testing. The diagnostic performance (positive predictive value) of the symptoms associated with a positive test could have been higher if, for example, RT-PCR tests had been combined with serological tests in our study.
Comparison with existing literature
The majority of patients with COVID-19 are thought to have mild to moderate disease and do not require hospitalization. However, it is of utmost importance to screen them in order to reduce the spread of the epidemic. Unfortunately, only a few studies described the clinical characteristics of these patients treated on an outpatient basis. [12–14] In the future, our results should help GPs to triage patients with infectious symptoms, especially in the winter period when the influenza virus is circulating.
We found that the three most frequently reported ENT and non-ENT symptoms in COVID-19 patients were dry throat (42%), loss of smell (36%) and loss of taste (31%), respectively fever (58%), cough (52%) and headache (45%). These prevalence data are quite different from those from a study conducted by ENT specialists in ambulatory patients recruited in French, Italian, Spanish, Belgian and Swiss hospitals (n=1566).  In this recently published study, the most frequent symptoms were headache (70%), loss of smell (70%), nasal obstruction (68%) and asthenia (63%). The data from our study also differed from those from studies conducted in China, which mainly involved hospitalized patients with severe infections. [7–11] For example, in the study by Huang et al (n=41 patients hospitalized in Wuhan), the most frequently reported symptoms were fever (98%), cough (76%) and dyspnea (55%),  while in the study by Wang et al (n=138 patients hospitalized in Wuhan), the most prevalent symptoms were fever (99%), fatigue (70%) and cough (59%).  The differences observed between these studies are likely explained by population differences. For the studies conducted in China, the patients were inpatients with severe infections (vs. outpatients with mild to moderate infections in our study). For the European study, a large proportion of these patients were included either following a consultation with a specialist (cardiologist, ENT, etc.) or following admission to the hospital emergency department. By contrast, our data came from patients who had consulted GPs, and self-referred health professionals. They thus likely represent a population of patients with milder presentations of SARS-CoV2 infection, typical of those in whom early identification through primary care will be of essence at the wake of the next epidemic wave.
As already suggested in our preliminary study,  we confirm that the two symptoms most strongly associated with a positive test were loss of taste and smell. Interestingly, the combination of these two symptoms results in an even stronger association. The adjusted OR was 6.5 for patients complaining of loss of taste and smell, while it was 6.7 for those complaining of either symptom. Several other authors have recently published similar results, particularly on European outpatient populations. [13–15,18,21] SARS-CoV-2 has been shown to have a particular tropism for the nerves of the ear, nose and throat system.  This is probably the reason why the proportion of patients with taste and smell disorders is higher in COVID-19 patients than in patients with other respiratory tract infections. The fact that in our study COVID-19 patients complained less frequently about stuffy nose than other patients (23% vs. 34%) is consistent with this hypothesis.
While the presence of a stuffy nose decreased the likelihood of a positive test, the presence of a dry nose increased it. These results are potentially interesting because, in combination with loss of taste and smell, they could theoretically increase the diagnostic performance of the ENT clinical evaluation.
We found that patients who tested positive were less likely to complain of dyspnea and diarrhea than patients who tested negative. This result is rather counter-intuitive as several authors showed that these two symptoms were relatively common in patients infected with CoV-2-SARS. [7–10,12,13] However, these were mainly data from hospital-based studies. The clinical pictures presented by these patients are not necessarily similar to those presented by outpatients with mild to moderate symptoms. For example, patients often require hospitalization because of oxygen desaturation due to lung involvement. Its high prevalence among inpatients certainly explains why they have more dyspnea than our community-based sample.
Implications for research and/or practice
The results of this study should be confirmed and refined in future studies, involving patients from various primary care context, to extend the external validity of these findings.
As explained above, we showed that taste and smell disorders were the most specific symptoms of CoV-2-SARS infection in our sample, and the specificity increased further when these two symptoms were combined. However, their diagnostic performance was not sufficient to confirm infection with sufficient safety in affected patients. Indeed, the positive predictive value (i.e. the probability of testing positive) was only 53% in patients with loss of taste, 50% in patients with loss of smell, 57% in the presence of both symptoms and 49% in the presence of at least one of the two symptoms. Furthermore, these diagnostic performances are expected to decrease as the prevalence of infection decreases.
Theoretically, it would be interesting to use the clinical characteristics of patients to promote targeted screening for CoV-2 SARS infection. However, our results suggesting a high risk of false positives do not encourage this approach across the board. This screening strategy could be used in cases of high prevalence of infection (e.g. typical symptoms in a second epidemic wave context) or in certain patients with a high probability of infection (e.g. typical symptoms and notion of close contact with an infected patient).