Network Analysis of Outpatients to Identify Predictive Symptoms and Combinations of Symptoms Associated With Positive/Negative SARS-CoV-2 Nasopharyngeal Swabs

Background: Limited data exist on early predictive clinical symptoms or combinations of symptoms that could be included in the case definition of coronavirus disease 2019 (COVID-19), particularly for mild-to-moderate disease in an outpatient setting. Methods: A cohort study of individuals presenting with clinical symptoms to one of the largest dedicated networks of COVID-19 test centers in Geneva, Switzerland, between March 2 and April 23, 2020. Individuals completed a symptom questionnaire, received a nurse-led check-up, and nasopharyngeal swabs were obtained. An analysis of clinical features predicting the positivity and negativity of the SARS-CoV-2 RT-PCR test was performed to determine the relationship between symptoms and their combinations. Results: Of 3,248 patients included (mean age, 42.2 years; 1,504 [46.3%] male), 713 (22%) had a positive RT-PCR; 1,351 (41.6%) consulted within 3 days of symptom onset. The strongest predictor of a positive SARS-CoV-2 RT-PCR was anosmia, particularly in early disease, followed by fever, myalgia, and cough. Symptoms predictive of a negative test were breathing difficulties, abdominal symptoms, thoracic pain and runny nose. Three distinct networks of symptoms were identified, but did not occur together: respiratory symptoms; systemic symptoms related to fever; and other systemic symptoms related to anosmia. Conclusions: Symptoms and networks of symptoms associated with a positive/negative SARS-CoV-2 RT-PCR are emerging and may help to guide targeted testing. Identification of early COVID-19-related symptoms alone or in combination can contribute to establish a clinical case definition and provide a basis for clinicians and public health authorities to distinguish it from other respiratory viruses early in the course of the disease, particularly in the outpatient setting.

Automated summary

This cohort study in Geneva, Switzerland, identified early clinical symptoms predictive of positive or negative SARS-CoV-2 RT-PCR results, with anosmia being the strongest predictor for a positive test. Symptoms like breathing difficulties, abdominal symptoms, thoracic pain, and runny nose were associated with a negative test. The study also found three distinct networks of symptoms including respiratory symptoms, systemic symptoms related to fever, and other systemic symptoms related to anosmia, which could help guide targeted testing for COVID-19.