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

ABSTRACTBackgroundFalse negative results of SARS-CoV-2 nucleic acid detection pose threats to COVID-19 patients and medical workers alike.ObjectiveTo 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.DesignRetrospective Cohort Study (Ethics number of Tongji Hospital: No. IRBID: TJ-20200320)SettingA database of outpatients in Tongji Hospital (University Hospital) from 15 January 2020 to 19 February 2020.Patients1,324 outpatients with COVID-19MeasurementsClinical 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.ResultsOf 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.LimitationData were generated in a large single-center study.ConclusionTesting 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 SourceNone.

Download Full-text

Scoring System for the Diagnosis of COVID-19

The Open Public Health Journal ◽

10.2174/1874944502013010413 ◽

2020 ◽

Vol 13 (1) ◽

pp. 413-414 ◽

Cited By ~ 1

Author(s):

Mohamed Farouk Allam

Keyword(s):

Scoring System ◽

Clinical Symptoms ◽

False Negative ◽

Nasopharyngeal Swab ◽

Rt Pcr ◽

Pcr Assay ◽

Negative Results ◽

False Negative Results ◽

Symptoms And Signs

Due to the international spread of COVID-19, the difficulty of collecting nasopharyngeal swab specimen from all suspected patients, the costs of RT-PCR and CT, and the false negative results of RT-PCR assay in 41% of COVID-19 patients, a scoring system is needed to classify the suspected patients in order to determine the need for follow-up, home isolation, quarantine or the conduction of further investigations. A scoring system is proposed as a diagnostic tool for suspected patients. It includes Epidemiological Evidence of Exposure, Clinical Symptoms and Signs, and Investigations (if available). This scoring system is simple, could be calculated in a few minutes, and incorporates the main possible data/findings of any patient.

Download Full-text

The application of viral nucleic acid detection and lung CT in COVID-19 diagnosis

10.37191/mapsci-jccr-1(2)-012 ◽

2020 ◽

Author(s):

Rui Hu

Keyword(s):

Nucleic Acid ◽

Clinical Symptoms ◽

Virus Disease ◽

False Negative ◽

False Negative Rate ◽

Diagnostic Methods ◽

Nucleic Acid Detection ◽

Viral Nucleic Acid ◽

Early Medical Intervention ◽

Lung Ct

The Corona Virus Disease 2019 (COVID-19) has the characteristics of fast propagation speed and strong pathogenicity and has attracted wide attention of people, medical workers, and researchers around the world. Accurate, rapid, and timely screening and diagnosis of COVID-19 is of great significance to control the development of the epidemic situation and save the lives of patients. Currently, the detection of viral nucleic acid and lung CT is the main screening and diagnostic methods of COVID-19. Nucleic acid detection has the advantages of fast, strong specificity and high sensitivity, but there is a certain false-negative rate. CT result of lung examination is visual, but it is not typical due to the uncertain time of clinical symptoms and the early medical intervention. Therefore, the diagnosis of COVID-19 should include a combination of epidemiological history, clinical symptoms, imaging, and laboratory tests.

Download Full-text

Exploring 'best practice' for nucleic acid detection of Neisseria gonorrhoeae

Sexual Health ◽

10.1071/sh07050 ◽

2008 ◽

Vol 5 (1) ◽

pp. 17 ◽

Cited By ~ 40

Author(s):

David M. Whiley ◽

Suzanne M. Garland ◽

Geoffrey Harnett ◽

Gary Lum ◽

David W. Smith ◽

...

Keyword(s):

Nucleic Acid ◽

Neisseria Gonorrhoeae ◽

Best Practice ◽

Current Knowledge ◽

False Negative ◽

High Sensitivity ◽

Nucleic Acid Detection ◽

Predictive Values ◽

Neisseria Species ◽

Negative Results

Nucleic acid detection tests (NADT) have considerable benefits for the detection of Neisseria gonorrhoeae (GC), including high sensitivity across a range of specimen types and use under widely differing settings and conditions. However, sexual health practitioners and others who use data generated by NADT for GC should be aware of some important limitations of these tests. False-positive results caused by cross reaction with commensal Neisseria species have been observed in many assays, and have lead to unacceptably low positive-predictive values in some patient populations. Further, false-negative results can be caused by GC sequence variation, with some gonococci lacking certain NADT target sequences. This review examines the issues associated with gonococcal NADT and considers best practice for use of these assays based on current knowledge. We emphasise the need for supplementary testing and extensive assay validation, and suggest appropriate strategies for these requirements irrespective of the setting in which they are used. Further, we highlight the need to maintain culture-based testing for certain specimen sites as well as for antimicrobial resistance surveillance.

Download Full-text

Phenothiazine Derivatives in Urine: "False Nagative Results" With the Forrest Color Test (FPN), and a Method for Their Elimination

Clinical Chemistry ◽

10.1093/clinchem/11.10.914 ◽

1965 ◽

Vol 11 (10) ◽

pp. 914-919

Author(s):

K N Campbell

Keyword(s):

False Negative ◽

False Positives ◽

Phenothiazine Derivatives ◽

Color Test ◽

False Negatives ◽

Delayed Reaction ◽

Negative Results ◽

False Negative Results ◽

Phenothiazine Drugs ◽

Urine Specimens

Abstract More than 100 Forrest color tests (FPN) were performed on urine specimens from patients taking phenothiazine drugs. The results obtained showed > 20% "false negatives" and 6% "false positives." A delayed reaction due to possible individual patient variation seems to have been the cause for false-negative results. These false negatives were shown to disappear when test readings were delayed for 1-5 min. Some false positives were due to liver dysfunction.

Download Full-text

Onychomycosis Infections

Journal of the American Podiatric Medical Association ◽

10.7547/15-136 ◽

2017 ◽

Vol 107 (4) ◽

pp. 280-286 ◽

Cited By ~ 11

Author(s):

Aditya K. Gupta ◽

Kerry-Ann Nakrieko

Keyword(s):

False Negative ◽

Kappa Statistic ◽

False Negatives ◽

Negative Results ◽

False Negative Results ◽

Repeated Sampling ◽

Polymerase Chain ◽

Serial Samples ◽

Repeated Samples ◽

Infecting Organisms

Background: Mycological culture is the traditional method for identifying infecting agents of onychomycosis despite high false-negative results, slower processing, and complications surrounding nondermatophyte mold (NDM) infections. Molecular polymerase chain reaction (PCR) methods are faster and suited for ascertaining NDM infections. Methods: To measure agreement between culture and PCR methods for identification of infecting species of suspected onychomycosis, single toenail samples from 167 patients and repeated serial samples from 43 patients with suspected onychomycosis were processed by culture and PCR for identification of 16 dermatophytes and five NDMs. Agreement between methods was quantified using the kappa statistic (κ). Results: The methods exhibited fair agreement for the identification of all infecting organisms (single samples: κ = 0.32; repeated samples: κ = 0.38). For dermatophytes, agreement was moderate (single samples: κ = 0.44; repeated samples: κ = 0.42). For NDMs, agreement was poor with single samples (κ = 0.16) but fair with repeated samples (κ = 0.25). Excluding false-negative reports from analyses improved agreement between methods in all cases except the identification of NDMs from single samples. Conclusions: Culture was three or four times more likely to report a false-negative result compared with PCR. The increased agreement between methods observed by excluding false-negative reports statistically clarifies and highlights the major discord caused by false-negative cultures. The increased agreement of NDM identification from poor to fair with repeated sampling along with their poor agreement in the single samples, with and without false-negatives, affirms the complications of NDM identification and supports the recommendation that serial samples help confirm the diagnosis of NDM infections.

Download Full-text

FALSE-NEGATIVE RESULTS IN SCREENING PROGRAMS

International Journal of Technology Assessment in Health Care ◽

10.1017/s0266462300105021 ◽

2001 ◽

Vol 17 (2) ◽

pp. 164-170 ◽

Cited By ~ 11

Author(s):

Mark Petticrew ◽

Amanda Sowden ◽

Deborah Lister-Sharp

Keyword(s):

Negative Impact ◽

Relevant Literature ◽

False Negative ◽

Quantitative Information ◽

Public Confidence ◽

Psychological Consequences ◽

False Negatives ◽

Screening Programs ◽

Negative Results ◽

False Negative Results

Objectives: Assessment of the appropriateness of screening programs involves consideration of the harms as well as the benefits. These harms include the risk of false-negative results, the consequences of which have remained underinvestigated. This paper reports the results of a systematic literature review that aimed to assess the medical psychological, economic, and legal consequences of false-negative results in national screening programs.Methods: The review included a comprehensive literature search and contact with experts to identify relevant literature. Most studies that were identified presented only anecdotal evidence. However, thirteen studies presented quantitative information on medical consequences of false negatives, eight studies presented information on psychological consequences, and two studies presented information on economic consequences.Results: The strength of evidence from most of the primary studies was low. There is some evidence, however, that false-negative results may have a large legal impact. There is also a consensus in the literature that false negatives may have a negative impact on public confidence on screening; evidence is however limited.Conclusions: False negatives are evident even in high-quality screening programs. They may have the potential to delay the detection of breast and cervical cancer, but there is little evidence to help in assessing their psychological consequences. They also may lead to legal action being taken by those affected and may reduce public confidence in screening. Their impact may be reduced by provision of full information to participants about the benefits and limitations of screening programs and by increasing public education on these issues.

Download Full-text

A case of SARS-CoV-2 carrier for 32 days with several times false negative nucleic acid tests

10.1101/2020.03.31.20045401 ◽

2020 ◽

Cited By ~ 6

Author(s):

Lingjie Song ◽

Guibao Xiao ◽

Xianqin Zhang ◽

Zhan Gao ◽

Shixia Sun ◽

...

Keyword(s):

Nucleic Acid ◽

Clinical Symptoms ◽

Early Stage ◽

Antiviral Treatment ◽

Immune Therapy ◽

False Negative ◽

Clinical Manifestations ◽

Nucleic Acid Detection ◽

Rt Pcr ◽

Nucleic Acid Tests

AbstractIn 2019, a novel coronavirus (SARS-CoV-2) was first discovered in Wuhan, Hubei, China, causing severe respiratory disease in humans, and has been identified as a public health emergency of international concern. With the spread of the virus, there are more and more false negative cases of RT-PCR nucleic acid detection in the early stage of potential infection. In this paper, we collected the epidemiological history, clinical manifestations, outcomes, laboratory results and images of a SARS-CoV-2 carrier with no significant past medical history. The patient was quarantined because of her colleague had been diagnosed. After the onset of clinical symptoms, chest CT results showed patchy ground-glass opacity (GGO) in her lungs, but it took a total of nine nucleic acid tests to confirm the diagnosis, among which the first eight RT-PCR results were negative or single-target positive. In addition to coughing up phlegm during her stay in the hospital, she did not develop chills, fever, abdominal pain, diarrhea and other clinical symptoms. Since initial antiviral treatment, the lung lesions were absorbed. But the sputum nucleic acid test was still positive. In combination with antiviral and immune therapy, the patient tested negative for the virus. Notably, SARS-CoV-2 was detected only in the lower respiratory tract samples (sputum) throughout the diagnosis and treatment period. This is a confirmed case of SARS-CoV-2 infection with common symptoms, and her diagnosis has undergone multiple false negatives, suggesting that it is difficult to identify certain carriers of the virus and that such patients may also increase the spread of the SARS-CoV-2.

Download Full-text

Prolonged nucleic acid conversion and false-negative RT-PCR results in Indonesian patients with COVID-19: A case series

10.21203/rs.3.rs-39961/v1 ◽

2020 ◽

Author(s):

Ika Trisnawati ◽

Riat Al Khair ◽

Aditya Rifqi Fauzi ◽

Gunadi

Keyword(s):

Nucleic Acid ◽

Male Patient ◽

False Negative ◽

Case Series ◽

Heart Rhythm ◽

X Rays ◽

Rt Pcr ◽

Negative Results ◽

False Negative Results ◽

Heart Rhythm Disorders

Abstract Background: Prolonged nucleic acid conversion and false-negative results of real-time reverse transcription polymerase chain reaction (RT-PCR) might occur in some patients with COVID-19 rather than recurrence of infection. Here, we reported four cases of COVID-19 with prolonged nucleic acid conversion and false-negative results of RT-PCR in our institution.Case presentation: Case 1: A 36-year-old-male patient complained of coughing up phlegm one week before admission. His chest X-rays showed mild pneumonia in the right lung. His swab test was confirmed positive for SARS-Cov-2. Besides the last two consecutive negative results, he also had negative results of RT-PCR twice (the 6th and 8th tests) from a total of 11 swab tests. Case 2: A 54-year-old-male patient complained of shortness of breath that worsened with activity. He had a comorbidity of diabetes. His chest X-rays showed inhomogeneous opacity on bilateral paracardial and lateral aspects. His swab test was confirmed positive for SARS-Cov-2. Besides the last two consecutive negative results, he also had negative results of RT-PCR once (the 5th test) from a total of 8 swab tests. Case 3: A 47-year-old man presented with complaints of fever, cough, sore throat, and diarrhea. He had comorbidities of asthma and heart rhythm disorders. His chest X-rays showed bilateral pneumonia. His swab test was confirmed positive for SARS-Cov-2. Besides the last two consecutive negative results, he also showed negative results of RT-PCR twice (the 4th and 6th tests) from a total of 11 swab tests. Case 4: A 56-year-old-female complained of lethargy and diarrhea. She has a history of hyperthyroidism. His chest X-rays showed bilateral pneumonia. She was confirmed positive for SARS-Cov-2. Besides the last two consecutive negative results, she also had negative results of RT-PCR twice (the 2nd and 10th tests) from a total of 14 swab tests.Conclusions: Our cases further confirmed the occurrence of prolonged nucleic acid conversion and the possibility of false negative results of RT-PCR in patients with COVID-19 instead of recurrence of infection. These findings might have an implication on the management of patients with COVID-19 who have already clinically and radiologically recovered, particularly related to subsequent spreading of the infection in the community.

Download Full-text

Conjunctival polymerase chain reaction-tests of 2019 novel coronavirus in patients in Shenyang,China

10.21203/rs.3.rs-17648/v1 ◽

2020 ◽

Author(s):

Li Xu ◽

Xinyue Zhang ◽

Wei Song ◽

Baijun Sun ◽

Jinping Mu ◽

...

Keyword(s):

Clinical Features ◽

Clinical Symptoms ◽

False Negative ◽

Suspected Case ◽

Negative Results ◽

False Negative Results ◽

Laboratory Results ◽

Polymerase Chain ◽

Novel Coronavirus ◽

Negative Detection

Abstract Background We report the laboratory results of conjunctival PCR-tests and some clinical features of these patients infected with COVID-19 in shenyang China.Methods We collected conjunctival samples of the patients to do the laboratory tests by PCR.Medical observed patients were enrolled if they had clinical symptoms. Then we analysed the PCR results and clinical features in order to find some relationships.Results The study include 14 confirmly diagnosed cases ,16 suspected cases and some medical observed patients.1 of the identified case coverted from suspected case.22 medical observed cases were removed because none of them converted to identified cases.1 of the suspected converted to identified case recently.All the conjunctival results of PCR-test were negative.Discussion The reasons of the negative detection results of PCR in conjunctival swabs were discussed.Conclusion Conjunctiva may be a transmission way of COVID-19.And ocular conjunctival swabs could be a diagnostic method for identifying the infection of COVID-19.Emphasis on the false-negative results is vital.

Download Full-text

Evaluating real-time PCR for the quantification of distinct pathogens and indicator organisms in environmental samples

Water Science & Technology ◽

10.2166/wst.2004.0065 ◽

2004 ◽

Vol 50 (1) ◽

pp. 263-270 ◽

Cited By ~ 32

Author(s):

M. Lebuhn ◽

M. Effenberger ◽

G. Garcés ◽

A. Gronauer ◽

P.A. Wilderer

Keyword(s):

Nucleic Acid ◽

Real Time ◽

Real Time Pcr ◽

Environmental Samples ◽

False Negative ◽

Indicator Organisms ◽

Negative Results ◽

False Negative Results ◽

Methodological Bias ◽

Reliable Quantification

We evaluated quantitative real-time PCR (qPCR) and RTqPCR (for RNA species) for their ability to quantify microorganisms and viruses in problematic environmental samples such as cattle manure, digester material, wastewater and soil. Important developments included a standard spiking approach which compensated for methodological bias and allowed sample-to-sample comparison and reliable quantification. Programme CeTe was developed to calculate endogenous concentrations of target organisms (nucleic acid copies) for each sample separately from the generated standard curves. The approach also permitted assessment of the detection limit of the complete method, including extraction. It varied from sample to sample, due to different extraction efficiencies and variable co-extraction of PCR inhibitors. False negative results were thereby avoided. By using this approach we were able to optimise a DNA extraction protocol from the different tested sample types. Protocols for the extraction of RNA species from environmental samples were also optimised. DNA was (almost) not degraded after lethal shock (autoclaving) in the sterile environment. In contrast, the parallel selective cultivation and qPCR results for various microbial parameters from an anaerobic digester chain suggested that DNA from decaying organisms was readily recycled in metabolically active environments. It may, therefore, be used to determine viable organisms in samples exhibiting substantial metabolic turnover. It is proposed that our standard spiking approach, including data evaluation by the program CeTe, should be considered in future standardisation and norms for the quantification of nucleic acid containing organisms in environmental and product samples.

Download Full-text