Abstract
BackgroundThe early clinical course of COVID-19 can be difficult to distinguish from other illnesses driving presentation to hospital. However, viral-specific PCR testing has limited sensitivity and results can take up to 72 h for operational reasons. We aimed to develop and validate two early-detection models for COVID-19, screening for the disease among patients attending the emergency department and the subset being admitted to hospital, using routinely collected health-care data (laboratory tests, blood gas measurements, and vital signs). These data are typically available within the first hour of presentation to hospitals in high-income and middle-income countries, within the existing laboratory infrastructure.MethodsWe trained linear and non-linear machine learning classifiers to distinguish patients with COVID-19 from pre-pandemic controls, using electronic health record data for patients presenting to the emergency department and admitted across a group of four teaching hospitals in Oxfordshire, UK (Oxford University Hospitals). Data extracted included presentation blood tests, blood gas testing, vital signs, and results of PCR testing for respiratory viruses. Adult patients (>18 years) presenting to hospital before Dec 1, 2019 (before the first COVID-19 outbreak), were included in the COVID-19-negative cohort; those presenting to hospital between Dec 1, 2019, and April 19, 2020, with PCR-confirmed severe acute respiratory syndrome coronavirus 2 infection were included in the COVID-19-positive cohort. Patients who were subsequently admitted to hospital were included in their respective COVID-19-negative or COVID-19-positive admissions cohorts. Models were calibrated to sensitivities of 70%, 80%, and 90% during training, and performance was initially assessed on a held-out test set generated by an 80:20 split stratified by patients with COVID-19 and balanced equally with pre-pandemic controls. To simulate real-world performance at different stages of an epidemic, we generated test sets with varying prevalences of COVID-19 and assessed predictive values for our models. We prospectively validated our 80% sensitivity models for all patients presenting or admitted to the Oxford University Hospitals between April 20 and May 6, 2020, comparing model predictions with PCR test results.FindingsWe assessed 155 689 adult patients presenting to hospital between Dec 1, 2017, and April 19, 2020. 114 957 patients were included in the COVID-negative cohort and 437 in the COVID-positive cohort, for a full study population of 115 394 patients, with 72 310 admitted to hospital. With a sensitive configuration of 80%, our emergency department (ED) model achieved 77·4% sensitivity and 95·7% specificity (area under the receiver operating characteristic curve [AUROC] 0·939) for COVID-19 among all patients attending hospital, and the admissions model achieved 77·4% sensitivity and 94·8% specificity (AUROC 0·940) for the subset of patients admitted to hospital. Both models achieved high negative predictive values (NPV; >98·5%) across a range of prevalences (≤5%). We prospectively validated our models for all patients presenting and admitted to Oxford University Hospitals in a 2-week test period. The ED model (3326 patients) achieved 92·3% accuracy (NPV 97·6%, AUROC 0·881), and the admissions model (1715 patients) achieved 92·5% accuracy (97·7%, 0·871) in comparison with PCR results. Sensitivity analyses to account for uncertainty in negative PCR results improved apparent accuracy (ED model 95·1%, admissions model 94·1%) and NPV (ED model 99·0%, admissions model 98·5%).InterpretationOur models performed effectively as a screening test for COVID-19, excluding the illness with high-confidence by use of clinical data routinely available within 1 h of presentation to hospital. Our approach is rapidly scalable, fitting within the existing laboratory testing infrastructure and standard of care of hospitals in high-income and middle-income countries.FundingWellcome Trust, University of Oxford, Engineering and Physical Sciences Research Council, National Institute for Health Research Oxford Biomedical Research Centre.
Highlights
An outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) led to the COVID-19 pandemic of 2020.1 The early clinical course of COVID-19, which often includes common symptoms such as fever and cough, can be challenging for clinicians to distinguish from other respiratory illnesses.[2,3,4]Testing for SARS-CoV-2, most commonly by real-time RT-PCR assay of nasopharyngeal swabs, has been widely adopted, but has limitations.[3,5,6] These include limited sensitivity,[5,7] a long turnaround time of up to 72 h, and requirements for specialist laboratory infrastructure and expertise.[8]
Adult patients (>18 years) presenting to hospital before Dec 1, 2019, were included in the COVID-19-negative cohort; those presenting to hospital between Dec 1, 2019, and April 19, 2020, with PCR-confirmed severe acute respiratory syndrome coronavirus 2 infection were included in the COVID-19-positive cohort
Models were calibrated to sensitivities of 70%, 80%, and 90% during training, and performance was initially assessed on a held-out test set generated by an 80:20 split stratified by patients with COVID-19 and balanced with pre-pandemic controls
Summary
Testing for SARS-CoV-2, most commonly by real-time RT-PCR assay of nasopharyngeal swabs, has been widely adopted, but has limitations.[3,5,6] These include limited sensitivity,[5,7] a long turnaround time of up to 72 h, and requirements for specialist laboratory infrastructure and expertise.[8] Studies have shown a significant proportion of asymptomatic carriage and limited specificity for common symptoms (fever and cough), hampering symptom-guided hospital triage.[9] an urgent clinical need exists for rapid, point-of-care identification of COVID-19 to support expedient delivery of care and to assist front-door triage and patient streaming for infection control purposes.[10]. The increasing use of electronic health-care record (EHR) systems has improved the richness of clinical datasets available to study COVID-19. High-throughput electronic data extraction and processing can enable curation of rich datasets, incorporating all clinical data available on presentation, and might combine with advanced machine learning techniques to produce a rapid screening tool for COVID-19 that fits within existing clinical pathways.[11,12]
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