False-negative RT-PCR for COVID-19 and a diagnostic risk score: a retrospective cohort study among patients admitted to hospital

Gupta-Wright, Ankur; Macleod, Colin Kenneth; Barrett, Jessica; Filson, Sarah Ann; Corrah, Tumena; Parris, Victoria; Sandhu, Gurjinder; Harris, Miriam; Tennant, Rachel; Vaid, Nidhi; Takata, Junko; Duraisingham, Sai; Gandy, Nemi; Chana, Harmeet; Whittington, Ashley; McGregor, Alastair; Papineni, Padmasayee

OBJECTIVE: To describe the characteristics and outcomes of patients with a clinical diagnosis of COVID-19 and false-negative SARS-CoV-2 reverse transcription-PCR (RT-PCR), and develop and internally validate a diagnostic risk score to predict risk of COVID-19 (including RT-PCR-negative COVID-19) among medical admissions. DESIGN: Retrospective cohort study. SETTING: Two hospitals within an acute NHS Trust in London, UK. PARTICIPANTS: All patients admitted to medical wards between 2 March and 3 May 2020. OUTCOMES: Main outcomes were diagnosis of COVID-19, SARS-CoV-2 RT-PCR results, sensitivity of SARS-CoV-2 RT-PCR and mortality during hospital admission. For the diagnostic risk score, we report discrimination, calibration and diagnostic accuracy of the model and simplified risk score and internal validation. RESULTS: 4008 patients were admitted between 2 March and 3 May 2020. 1792 patients (44.8%) were diagnosed with COVID-19, of whom 1391 were SARS-CoV-2 RT-PCR positive and 283 had only negative RT-PCRs. Compared with a clinical reference standard, sensitivity of RT-PCR in hospital patients was 83.1% (95% CI 81.2%–84.8%). Broadly, patients with false-negative RT-PCR COVID-19 and those confirmed by positive PCR had similar demographic and clinical characteristics but lower risk of intensive care unit admission and lower in-hospital mortality (adjusted OR 0.41, 95% CI 0.27–0.61). A simple diagnostic risk score comprising of age, sex, ethnicity, cough, fever or shortness of breath, National Early Warning Score 2, C reactive protein and chest radiograph appearance had moderate discrimination (area under the receiver–operator curve 0.83, 95% CI 0.82 to 0.85), good calibration and was internally validated. CONCLUSION: RT-PCR-negative COVID-19 is common and is associated with lower mortality despite similar presentation. Diagnostic risk scores could potentially help triage patients requiring admission but need external validation.