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

Abstract

ObjectiveTo 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.DesignRetrospective cohort study.SettingTwo hospitals within an acute NHS Trust in London, UK.ParticipantsAll patients admitted to medical wards between 2 March and 3 May 2020.OutcomesMain 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.Results4008 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.ConclusionRT-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.

COVID-19: comparison lung CT signs and biochemical parameters in the groups of patients with three-time positive RT-PCR and with triple negative RT-PCR test during the period of hospitalization

“…In addition to this study, there are numerous papers and articles about patients with negative PCR test, but clinically and radiologically confirmed COVID-19 [16,17]. Data on sensitivity of the "gold standard" of COVID-19 diagnostics vary from 46% to 83.1% in different studies [16,17]. Some studies suggest that the PCR test sensitivity is high at the beginning of the disease only: for the first 5 days after the onset of symptoms, the clinical sensitivity remains above 90%; then between days 6 and 8, the clinical sensitivity of PCR varies from 84% to 76%; in the following days, the sensitivity decreases; and by day 18, the sensitivity decreases below 50% [11].…”

“…In addition to this study, there are numerous papers and articles about patients with negative PCR test, but clinically and radiologically confirmed COVID-19 [16,17]. Data on sensitivity of the "gold standard" of COVID-19 diagnostics vary from 46% to 83.1% in different studies [16,17].…”

“…It cannot be excluded that the initial entry of the virus into the body through the carrier proteins in the olfactory epithelium may increase the overall viral load and worsen the course of the disease. Thus, in the Ankur Gupta-Wright et al study, outcomes were worse in patients with COVID-19 confirmed by RT-PCR compared to those with false-negative RT-PCR; the proportion of patients hospitalized in the ICU was higher [16].…”

“…Помимо данного исследования существует немало публикаций и статей о больных, у которых тест ПЦР был отрицательным, но COVID-19 был подтвержден клинически и рентгенологически [16,17]. Данные о чувствительности "золотого стандарта" диагностики COVID-19 варьируют в разных исследованиях от 46 до 83,1% [16,17].…”

Auditing the efficacy of prophylactic measures against Covid-19 amongst Healthcare workers in India

“…This was considered separately, due to high false-negative RT-PCR rates. 2 The study included a total of 834 healthcare workers including general practitioners (GPs), specialists, nurses, dentists, paraclinical support staff, and practitioners of traditional(alternative) medicine. The mean age was 44.8 ± 12.1 years.…”