scholarly journals Estimate false‐negative RT‐PCR rates for SARS‐CoV‐2. A systematic review and meta‐analysis

Author(s):  
Valentina Pecoraro ◽  
Antonella Negro ◽  
Tommaso Pirotti ◽  
Tommaso Trenti
2020 ◽  
Author(s):  
Mohammad Karam ◽  
Sulaiman Althuwaikh ◽  
Mohammad Alazemi ◽  
Ahmad Abul ◽  
Amrit Hayre ◽  
...  

AbstractPurposeTo compare the performance of chest computed tomography (CT) scan versus reverse transcription polymerase chain reaction (RT-PCR) in the initial diagnostic assessment of coronavirus disease 2019 (COVID-19) patients.MethodsA systematic review and meta-analysis were performed as per the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines. A search of electronic information was conducted to identify all relevant studies comparing the diagnostic performance of chest CT scan versus RT-PCR in COVID-19 suspected cases. Sensitivity, specificity and accuracy were primary outcome measures. Secondary outcome measures included other test performance characteristics, discrepant findings between both investigations and main chest CT findings. Random effects modelling was used for the analyses.ResultsEight non-randomised retrospective studies enrolling 1910 patients were identified. Chest CT was more sensitive but less specific than RT-PCR. Accuracy was not statistically significantly different between chest CT and RT-PCR for the identification and exclusion of COVID-19 cases (Odds Ratio [OR] = 0.40, P = 0.15) in the context of hospitalised patients in a pandemic. Chest CT was shown to detect patients with false-negative RT-PCR results and true positives. Ground-glass opacities and consolidations were the most common chest CT manifestations.ConclusionsChest CT is not superior to RT-PCR for the initial detection of COVID-19 and has more false positives. It is likely to be useful in confirming COVID-19 in patients with a suspicious clinical presentation, but who have a false-negative SARS-CoV-2 RT-PCR test.Key Points‐Chest computed tomography (CT) is more sensitive but less specific in detecting and excluding coronavirus disease 2019 (COVID-19) when compared to reverse transcription polymerase chain reaction (RT-PCR).‐Accuracy of chest CT is not significantly different from RT-PCR for COVID-19 cases.‐Chest CT can detect false-negative and true-positive RT-PCR cases.


2021 ◽  
Author(s):  
Valentina Pecoraro ◽  
Antonella Negro ◽  
Tommaso Pirotti ◽  
Tommaso Trenti

2021 ◽  
Vol 10 (7) ◽  
pp. 1543
Author(s):  
Morwenn Le Boulc’h ◽  
Julia Gilhodes ◽  
Zara Steinmeyer ◽  
Sébastien Molière ◽  
Carole Mathelin

Background: This systematic review aimed at comparing performances of ultrasonography (US), magnetic resonance imaging (MRI), and fluorodeoxyglucose positron emission tomography (PET) for axillary staging, with a focus on micro- or micrometastases. Methods: A search for relevant studies published between January 2002 and March 2018 was conducted in MEDLINE database. Study quality was assessed using the QUality Assessment of Diagnostic Accuracy Studies checklist. Sensitivity and specificity were meta-analyzed using a bivariate random effects approach; Results: Across 62 studies (n = 10,374 patients), sensitivity and specificity to detect metastatic ALN were, respectively, 51% (95% CI: 43–59%) and 100% (95% CI: 99–100%) for US, 83% (95% CI: 72–91%) and 85% (95% CI: 72–92%) for MRI, and 49% (95% CI: 39–59%) and 94% (95% CI: 91–96%) for PET. Interestingly, US detects a significant proportion of macrometastases (false negative rate was 0.28 (0.22, 0.34) for more than 2 metastatic ALN and 0.96 (0.86, 0.99) for micrometastases). In contrast, PET tends to detect a significant proportion of micrometastases (true positive rate = 0.41 (0.29, 0.54)). Data are not available for MRI. Conclusions: In comparison with MRI and PET Fluorodeoxyglucose (FDG), US is an effective technique for axillary triage, especially to detect high metastatic burden without upstaging majority of micrometastases.


Author(s):  
Faith Zhu ◽  
Carlos Zozaya ◽  
Qi Zhou ◽  
Charmaine De Castro ◽  
Prakesh S Shah

ObjectiveTo systematically review and meta-analyse the rate of SARS-CoV-2 genome identification and the presence of SARS-CoV-2 antibodies in breastmilk of mothers with COVID-19.DesignA systematic review of studies published between January 2019 and October 2020 without study design or language restrictions.SettingData sourced from Ovid Embase Classic+Embase, PubMed, Web of Science, Scopus, relevant bibliographies and the John Hopkins University COVID-19 database.PatientsMothers with confirmed COVID-19 and breastmilk tested for SARS-CoV-2 by RT-PCR or for anti-SARS-CoV-2 antibodies.Main outcome measuresPresence of SARS-CoV-2 genome and antibodies in breastmilk.ResultsWe included 50 articles. Twelve out of 183 women from 48 studies were positive for SARS-CoV-2 genome in their breastmilk (pooled proportion 5% (95% CI 2% to 15%; I2=48%)). Six infants (50%) of these 12 mothers tested positive for SARS-CoV-2, with one requiring respiratory support. Sixty-one out of 89 women from 10 studies had anti-SARS-CoV-2 antibody in their breastmilk (pooled proportion 83% (95% CI 32% to 98%; I2=88%)). The predominant antibody detected was IgA.ConclusionsSARS-CoV-2 genome presence in breastmilk is uncommon and is associated with mild symptoms in infants. Anti-SARS-CoV-2 antibodies may be a more common finding. Considering the low proportion of SARS-CoV-2 genome detected in breastmilk and its lower virulence, mothers with COVID-19 should be supported to breastfeed.


Author(s):  
Nicole Ngai Yung Tsang ◽  
Hau Chi So ◽  
Ka Yan Ng ◽  
Benjamin J Cowling ◽  
Gabriel M Leung ◽  
...  

Diagnostics ◽  
2021 ◽  
Vol 11 (2) ◽  
pp. 363
Author(s):  
Vânia M. Moreira ◽  
Paulo Mascarenhas ◽  
Vanessa Machado ◽  
João Botelho ◽  
José João Mendes ◽  
...  

The rapid and accurate testing of SARS-CoV-2 infection is still crucial to mitigate, and eventually halt, the spread of this disease. Currently, nasopharyngeal swab (NPS) and oropharyngeal swab (OPS) are the recommended standard sampling techniques, yet, these have some limitations such as the complexity of collection. Hence, several other types of specimens that are easier to obtain are being tested as alternatives to nasal/throat swabs in nucleic acid assays for SARS-CoV-2 detection. This study aims to critically appraise and compare the clinical performance of RT-PCR tests using oral saliva, deep-throat saliva/posterior oropharyngeal saliva (DTS/POS), sputum, urine, feces, and tears/conjunctival swab (CS) against standard specimens (NPS, OPS, or a combination of both). In this systematic review and meta-analysis, five databases (PubMed, Scopus, Web of Science, ClinicalTrial.gov and NIPH Clinical Trial) were searched up to the 30th of December, 2020. Case-control and cohort studies on the detection of SARS-CoV-2 were included. The methodological quality was assessed using the Quality Assessment of Diagnostic Accuracy Studies 2 (QUADAS 2). We identified 1560 entries, 33 of which (1.1%) met all required criteria and were included for the quantitative data analysis. Saliva presented the higher accuracy, 92.1% (95% CI: 70.0–98.3), with an estimated sensitivity of 83.9% (95% CI: 77.4–88.8) and specificity of 96.4% (95% CI: 89.5–98.8). DTS/POS samples had an overall accuracy of 79.7% (95% CI: 43.3–95.3), with an estimated sensitivity of 90.1% (95% CI: 83.3–96.9) and specificity of 63.1% (95% CI: 36.8–89.3). The remaining index specimens could not be adequately assessed given the lack of studies available. Our meta-analysis shows that saliva samples from the oral region provide a high sensitivity and specificity; therefore, these appear to be the best candidates for alternative specimens to NPS/OPS in SARS-CoV-2 detection, with suitable protocols for swab-free sample collection to be determined and validated in the future. The distinction between oral and extra-oral salivary samples will be crucial, since DTS/POS samples may induce a higher rate of false positives. Urine, feces, tears/CS and sputum seem unreliable for diagnosis. Saliva testing may increase testing capacity, ultimately promoting the implementation of truly deployable COVID-19 tests, which could either work at the point-of-care (e.g. hospitals, clinics) or at outbreak control spots (e.g., schools, airports, and nursing homes).


Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 5314-5314
Author(s):  
Heloisa P. Soares ◽  
Rodrigo Santucci ◽  
Ambuj Kumar ◽  
Benjamin Djulbegovic ◽  
Joao Glasberg ◽  
...  

Abstract Background: The identification of occult micrometastatic disease is potentially important in management of breast cancer (BC) patients. Therefore, detection of cytokeratin 19 (CK-19) and others molecular markers using reverse transcriptase polymerase chain reaction (RT-PCR)-based techniques to detect micrometastases could have significant implications in prevention, early detection and treatment of breast cancer. Objective: To assess the diagnostic specificity and sensitivity of detection of CK-19 in the peripheral blood (PB) of BC patients as well as to assess its relation to prognostic factors and implication on survival. Methods: We conducted a systematic review/meta-analysis of all studies that analyzed CK-19 in the PB of BC patients. We searched MEDLINE, LILACS and Cochrane Database of Systematic Reviews (last search June 2004). Studies that had at least 10 BC patients and controls and evaluated the presence of CK-19 in PB using RT-PCR were included in this review. Diagnostic sensitivity was defined as the percentage of detection of CK-19 in patients with histological proven diagnosis of breast cancer. The specificity was defined as the percentage of negative tests for CK-19 in the control group (healthy individuals or non breast cancer patients). Results: Out of 1842 relevant studies that were identified, 26 met our inclusion criteria, enrolling 2398 patients (1176 treatment and 1222 controls). Results showed that PCR had an overall diagnostic sensitivity of 0.39 (95% CI: 0.36–0.42) and diagnostic specificity of 0.83 (95% CI: 0.76–0.87) regardless of the breast cancer stage. Six studies researched the association between CK-19 and well established prognostic factors (i.e. positive axillary lymph nodes, hormonal receptors, tumor size); however data were not available for quantitative synthesis. Survival was poorly reported making impossible to generate any conclusion about the implication of detection of CK-19 on prognosis. When studies were critically appraised, we also identified many methodological weaknesses in the design, conduct and the analysis of these studies (e.g. use of multiple control arms, use of non-consecutive patients, different timing of sample collection, inclusion of all stages of breast cancer and differential work-up in the study & control groups) hence resulting in biased findings due to selection, verification, detection and spectrum bias. Conclusion: The existing body of evidence regarding the assessment and prognostic value of CK-19 using RT-PCR techniques is poor and needs ample improvement before the initiation of its clinical application.


2015 ◽  
Vol 53 (12) ◽  
pp. 3738-3749 ◽  
Author(s):  
Caroline Chartrand ◽  
Nicolas Tremblay ◽  
Christian Renaud ◽  
Jesse Papenburg

Respiratory syncytial virus (RSV) rapid antigen detection tests (RADT) are extensively used in clinical laboratories. We performed a systematic review and meta-analysis to evaluate the accuracy of RADTs for diagnosis of RSV infection and to determine factors associated with accuracy estimates. We searched EMBASE and PubMed for diagnostic-accuracy studies of commercialized RSV RADTs. Studies reporting sensitivity and specificity data compared to a reference standard (reverse transcriptase PCR [RT-PCR], immunofluorescence, or viral culture) were considered. Two reviewers independently extracted data on study characteristics, diagnostic-accuracy estimates, and study quality. Accuracy estimates were pooled using bivariate random-effects regression models. Heterogeneity was investigated with prespecified subgroup analyses. Seventy-one articles met inclusion criteria. Overall, RSV RADT pooled sensitivity and specificity were 80% (95% confidence interval [CI], 76% to 83%) and 97% (95% CI, 96% to 98%), respectively. Positive- and negative-likelihood ratios were 25.5 (95% CI, 18.3 to 35.5) and 0.21 (95% CI, 0.18 to 0.24), respectively. Sensitivity was higher in children (81% [95% CI, 78%, 84%]) than in adults (29% [95% CI, 11% to 48%]). Because of this disparity, further subgroup analyses were restricted to pediatric data (63 studies). Test sensitivity was poorest using RT-PCR as a reference standard and highest using immunofluorescence (74% versus 88%;P< 0.001). Industry-sponsored studies reported significantly higher sensitivity (87% versus 78%;P= 0.01). Our results suggest that the poor sensitivity of RSV RADTs in adults may preclude their use in this population. Furthermore, industry-sponsored studies and those that did not use RT-PCR as a reference standard likely overestimated test sensitivity.


2021 ◽  
Author(s):  
Emmanuel Oladipo Babafemi

Abstract Background: COVID-19 has spread globally since its discovery in Hubei province, China in December 2019 and became pandemic in 2020. COVID-19 is a new betacoronavirus and a variant of severe acute respiratory syndrome coronavirus 2 (SARA- CoV-2). Rapid, accurate and reliable diagnosis of COVID-19 will prevent the spread and allow for appropriate management. The main objective of this systematic review is to identify, appraise and summarise the published evidence on the diagnostic performance and effectiveness of SARS-CoV-2 virus in the diagnosis of current or previous COVID-19 using real-time polymerase chain reaction (RT-PCR) assay in low-and middle-income countries (LMICs). Methods: We will search MEDLINE/PubMed, EMBASE, BIOSIS, LILACS, Cochrane Infectious Diseases Group Specialised Register (CIDG SR), Global Health, and CINAHL for published studies for the diagnosis of COVID-19 using real-time polymerase chain reaction assay in LMICs There will be no restriction regarding the language, date of publication, and publication status. We will include retrospective, cross-sectional and cohort observational studies will be included in the review. Selection of studies, data extraction and management, assessment of risk of bias, and quality of evidence will be performed by two independent reviewers (EB and BC). A third researcher (GM) will be consulted in case of discrepancies. Depending on the availability and quality of the data, a meta-analysis will be performed. Otherwise, findings will be qualitatively reported. Discussion: To our knowledge, this is the first systematic review and meta-analysis to assess the uptake of RT-PCR assay for SARS-CoV-2 detection from clinical samples in human in LMICs. This review will make available evidence on the uptake, accuracy, approach, and interpretation of results of this assay in the context of COVID-19 diagnosis which will meet an urgent need, considering the diagnostic challenges of RT-PCR assay for COVID-19 diagnosis in humans. Systematic review registration: PROSPERO CRD42021271894


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