Analysis and Prediction of COVID-19 Patients’ False Negative Results for SARS-CoV-2 Detection with Pharyngeal Swab Specimen: A Retrospective Study

Abstract

Background: False negative results of SARS-CoV-2 nucleic acid detection pose threats to COVID-19 patients and medical workers alike.Objective: To develop multivariate models to determine clinical characteristics that contribute to false negative results of SARS-CoV-2 nucleic acid detection, and use them to predict false negative results as well as time windows for testing positive. Design: Retrospective Cohort Study (Ethics number of Tongji Hospital Patients: 1,324 outpatients with COVID-19Measurements: Clinical information on CT imaging reports, blood routine tests, and clinic symptoms were collected. A multivariate logistic regression was used to explain and predict false negative testing results of SARS-CoV-2 detection. A multivariate accelerated failure model was used to analyze and predict delayed time windows for testing positive. Results:Of the 1,324 outpatients who diagnosed of COVID-19, 633 patients tested positive in their first SARS-CoV-2 nucleic acid test (47.8%), with a mean age of 51 years (SD=14.9); the rest, which had a mean age of 47 years (SD=15.4), tested negative in the first test. "Ground glass opacity" in a CT imaging report was associated with a lower chance of false negatives (aOR, 0.56), and reduced the length of time window for testing positive by 26%. "Consolidation" was associated with a higher chance of false negatives (aOR, 1.57), and extended the length of time window for testing positive by 44%. In blood routine tests, basophils (aOR, 1.28) and eosinophils (aOR, 1.29) were associated with a higher chance of false negatives, and were found to extend the time window for testing positive by 23% and 41%, respectively. Age and gender also affected the significantly.Limitation: Data were generated in a large single-center study. Conclusion:Testing outcome and positive window of SARS-CoV-2 detection for COVID-19 patients were associated with CT imaging results, blood routine tests, and clinical symptoms. Taking into account relevant information in CT imaging reports, blood routine tests, and clinical symptoms helped reduce a false negative testing outcome. The predictive AFT model, what we believe to be one of the first statistical models for predicting time window of SARS-CoV-2 detection, could help clinicians improve the accuracy and efficiency of the diagnosis, and hence, optimizes the timing of nucleic acid detection and alleviates the shortage of nucleic acid detection kits around the world. Primary Funding Source: None.All rights reserved. No reuse allowed without permission.(which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. refinement of this model could be achieved by including novel clinical predictors.

AGA Institute Rapid Review of the Gastrointestinal and Liver Manifestations of COVID-19, Meta-Analysis of International Data, and Recommendations for the Consultative Management of Patients with COVID-19

“…A total of 43 studies including 10,676 COVID-19 patients (confirmed by laboratory real-time reverse transcription polymerase chain reaction [RT-PCR] testing) were included in the overall analysis. [20][21][22][23][24][25][26][27][28][29][30][31][32][33][34][35]37,38,41,42,45,47,[49][50][51][52][53][54][55]58,59,[62][63][64][65][66][67][68][69][70][71]73,76 The pooled prevalence of diarrhea symptoms across these studies was 7.7% (95% CI, 7.2%-8.2%). When analyzing by country (studies from China vs studies from other countries), the pooled prevalence of diarrhea in studies from countries other than China was much higher at 18.3% (95% CI, 16.6%-20.1%).…”

“…[20][21][22][23][25][26][27][28]30,[33][34][35]38,41,42,[44][45][46][49][50][51][52][53][54][55]60,[62][63][64][65][66][67][68][70][71][72][73][74]76 In 3 studies including 1701 outpatients, the pooled prevalence was 4.0% (95% CI, 3.1%-5.1%). 31,59,63 As part of the sensitivity analysis, we identified 35 studies including 9717 patients that described diarrhea, and explicitly reported that it was one of the initial presenting sympto ms. [20][21][22][23][26][27][28]31,…”

Diagnosis, Prevention, and Treatment of Thromboembolic Complications in COVID-19: Report of the National Institute for Public Health of the Netherlands

“…The diagnosis of COVID-19 is confirmed by a positive reverse transcriptase polymerase chain reaction (RT-PCR) from nose, throat, sputum or bronchoalveolar lavage. The sensitivity of this test is suboptimal (50-80%), probably due to sampling error, low viral loads as well as timing of the sample in the disease course (3,4). In most COVID-19 patients, non-contrast chest CTscanning shows bilateral ground glass opacities with a peripheral and basal distribution.…”

Asymptomatic Patients with Novel Coronavirus Disease (COVID-19)

“…CT: computed tomography the gold standard for the diagnosis of COVID-19, false negative test results are not too low because of many factors such as test kit, sampling tube, specimen sampling, drugs administered to patients etc. (5). Chest CT is of great value in the diagnosis of COVID-19 because of its simplicity and ease, especially in patients with or without clinical symptoms (3,6,7).…”