Computing SARS-CoV-2 Infection Risk From Symptoms, Imaging, and Test Data: Diagnostic Model Development

BACKGROUND: Assigning meaningful probabilities of SARS-CoV-2 infection risk presents a diagnostic challenge across the continuum of care. OBJECTIVE: The aim of this study was to develop and clinically validate an adaptable, personalized diagnostic model to assist clinicians in ruling in and ruling out COVID-19 in potential patients. We compared the diagnostic performance of probabilistic, graphical, and machine learning models against a previously published benchmark model. METHODS: We integrated patient symptoms and test data using machine learning and Bayesian inference to quantify individual patient risk of SARS-CoV-2 infection. We trained models with 100,000 simulated patient profiles based on 13 symptoms and estimated local prevalence, imaging, and molecular diagnostic performance from published reports. We tested these models with consecutive patients who presented with a COVID-19–compatible illness at the University of California San Diego Medical Center over the course of 14 days starting in March 2020. RESULTS: We included 55 consecutive patients with fever (n=43, 78%) or cough (n=42, 77%) presenting for ambulatory (n=11, 20%) or hospital care (n=44, 80%). In total, 51% (n=28) were female and 49% (n=27) were aged <60 years. Common comorbidities included diabetes (n=12, 22%), hypertension (n=15, 27%), cancer (n=9, 16%), and cardiovascular disease (n=7, 13%). Of these, 69% (n=38) were confirmed via reverse transcription-polymerase chain reaction (RT-PCR) to be positive for SARS-CoV-2 infection, and 20% (n=11) had repeated negative nucleic acid testing and an alternate diagnosis. Bayesian inference network, distance metric learning, and ensemble models discriminated between patients with SARS-CoV-2 infection and alternate diagnoses with sensitivities of 81.6%-84.2%, specificities of 58.8%-70.6%, and accuracies of 61.4%-71.8%. After integrating imaging and laboratory test statistics with the predictions of the Bayesian inference network, changes in diagnostic uncertainty at each step in the simulated clinical evaluation process were highly sensitive to location, symptom, and diagnostic test choices. CONCLUSIONS: Decision support models that incorporate symptoms and available test results can help providers diagnose SARS-CoV-2 infection in real-world settings.