scholarly journals Effectiveness of tests to detect the presence of SARS-CoV-2 virus, and antibodies to SARS-CoV-2, to inform COVID-19 diagnosis: a rapid systematic review

2020 ◽  
pp. bmjebm-2020-111511 ◽  
Author(s):  
David Jarrom ◽  
Lauren Elston ◽  
Jennifer Washington ◽  
Matthew Prettyjohns ◽  
Kimberley Cann ◽  
...  

ObjectivesWe undertook a rapid systematic review with the aim of identifying evidence that could be used to answer the following research questions: (1) What is the clinical effectiveness of tests that detect the presence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) to inform COVID-19 diagnosis? (2) What is the clinical effectiveness of tests that detect the presence of antibodies to the SARS-CoV-2 virus to inform COVID-19 diagnosis?Design and settingSystematic review and meta-analysis of studies of diagnostic test accuracy. We systematically searched for all published evidence on the effectiveness of tests for the presence of SARS-CoV-2 virus, or antibodies to SARS-CoV-2, up to 4 May 2020, and assessed relevant studies for risks of bias using the QUADAS-2 framework.Main outcome measuresMeasures of diagnostic accuracy (sensitivity, specificity, positive/negative predictive value) were the main outcomes of interest. We also included studies that reported influence of testing on subsequent patient management, and that reported virus/antibody detection rates where these facilitated comparisons of testing in different settings, different populations or using different sampling methods.Results38 studies on SARS-CoV-2 virus testing and 25 studies on SARS-CoV-2 antibody testing were identified. We identified high or unclear risks of bias in the majority of studies, most commonly as a result of unclear methods of patient selection and test conduct, or because of the use of a reference standard that may not definitively diagnose COVID-19. The majority were in hospital settings, in patients with confirmed or suspected COVID-19 infection. Pooled analysis of 16 studies (3818 patients) estimated a sensitivity of 87.8% (95% CI 81.5% to 92.2%) for an initial reverse-transcriptase PCR test. For antibody tests, 10 studies reported diagnostic accuracy outcomes: sensitivity ranged from 18.4% to 96.1% and specificity 88.9% to 100%. However, the lack of a true reference standard for SARS-CoV-2 diagnosis makes it challenging to assess the true diagnostic accuracy of these tests. Eighteen studies reporting different sampling methods suggest that for virus tests, the type of sample obtained/type of tissue sampled could influence test accuracy. Finally, we searched for, but did not identify, any evidence on how any test influences subsequent patient management.ConclusionsEvidence is rapidly emerging on the effectiveness of tests for COVID-19 diagnosis and management, but important uncertainties about their effectiveness and most appropriate application remain. Estimates of diagnostic accuracy should be interpreted bearing in mind the absence of a definitive reference standard to diagnose or rule out COVID-19 infection. More evidence is needed about the effectiveness of testing outside of hospital settings and in mild or asymptomatic cases. Implementation of public health strategies centred on COVID-19 testing provides opportunities to explore these important areas of research.

2020 ◽  
Author(s):  
David Jarrom ◽  
Lauren Elston ◽  
Jennifer Washington ◽  
Matthew Prettyjohns ◽  
Kimberley Cann ◽  
...  

Objectives: We undertook a rapid systematic review with the aim of identifying evidence that could be used to answer the following research questions: (1) What is the clinical effectiveness of tests that detect the presence of severe acute respiratory syndrome coronavirus 2 (SARS−CoV−2) to inform COVID−19 diagnosis? (2) What is the clinical effectiveness of tests that detect the presence of antibodies to the SARS−CoV−2 virus to inform COVID−19 diagnosis? Design: systematic review and meta−analysis of studies of diagnostic test accuracy. We systematically searched for all published evidence on the effectiveness of tests for the presence of SARS−CoV−2 virus, or antibodies to SARS−CoV−2, up to 4 May 2020, and assessed relevant studies for risks of bias using the QUADAS−2 framework. Main outcome measures: measures of diagnostic accuracy (sensitivity, specificity, positive/negative predictive value) were the main outcomes of interest. We also included studies that reported influence of testing on subsequent patient management, and that reported virus/antibody detection rates where these facilitated comparisons of testing in different settings, different populations, or using different sampling methods. Results: 38 studies on SARS−CoV−2 virus testing and 25 studies on SARS−CoV−2 antibody testing were identified. We identified high or unclear risks of bias in the majority of studies, most commonly as a result of unclear methods of patient selection and test conduct, or because of the use of a reference standard that may not definitively diagnose COVID−19. The majority were in hospital settings, in patients with confirmed or suspected COVID−19 infection. Pooled analysis of 16 studies (3818 patients) estimated a sensitivity of 87.8% (95% confidence interval 81.5% to 92.2%) for an initial reverse-transcriptase polymerase chain reaction test. For antibody tests, ten studies reported diagnostic accuracy outcomes: sensitivity ranged from 18.4% to 96.1% and specificity 88.9% to 100%. However, the lack of a true reference standard for SARS−CoV−2 diagnosis makes it challenging to assess the true diagnostic accuracy of these tests. Eighteen studies reporting different sampling methods suggest that for virus tests, the type of sample obtained/type of tissue sampled could influence test accuracy. Finally we searched for, but did not identify, any evidence on how any test influences subsequent patient management. Conclusions: Evidence is rapidly emerging on the effectiveness of tests for COVID−19 diagnosis and management, but important uncertainties about their effectiveness and most appropriate application remain. Estimates of diagnostic accuracy should be interpreted bearing in mind the absence of a definitive reference standard to diagnose or rule out COVID−19 infection. More evidence is needed about the effectiveness of testing outside of hospital settings and in mild or asymptomatic cases. Implementation of public health strategies centred on COVID−19 testing provides opportunities to explore these important areas of research.


2016 ◽  
Vol 17 (1) ◽  
pp. 3-8 ◽  
Author(s):  
S. Buczinski ◽  
G. Fecteau ◽  
M. Chigerwe ◽  
J. M. Vandeweerd

AbstractCalves are highly dependent of colostrum (and antibody) intake because they are born agammaglobulinemic. The transfer of passive immunity in calves can be assessed directly by dosing immunoglobulin G (IgG) or by refractometry or Brix refractometry. The latter are easier to perform routinely in the field. This paper presents a protocol for a systematic review meta-analysis to assess the diagnostic accuracy of refractometry or Brix refractometry versus dosage of IgG as a reference standard test. With this review protocol we aim to be able to report refractometer and Brix refractometer accuracy in terms of sensitivity and specificity as well as to quantify the impact of any study characteristic on test accuracy.


BMJ Open ◽  
2019 ◽  
Vol 9 (4) ◽  
pp. e025790 ◽  
Author(s):  
Rebecca Beynon ◽  
Martha Maria Christine Elwenspoek ◽  
Athena Sheppard ◽  
John Nicholas Higgins ◽  
Angelos G Kolias ◽  
...  

ObjectiveLumbar radiculopathy (LR) often manifests as pain in the lower back radiating into one leg (sciatica). Unsuccessful back surgery is associated with significant healthcare costs and risks to patients. This review aims to examine the diagnostic accuracy of selective nerve root blocks (SNRBs) to identify patients most likely to benefit from lumbar decompression surgery.DesignSystematic review of diagnostic test accuracy studies.Eligibility criteriaPrimary research articles using a patient population with low back pain and symptoms in the leg, SNRB administered under radiological guidance as index test, and any reported reference standard for the diagnosis of LR.Information sourcesMEDLINE (Ovid), MEDLINE In-Process & Other Non-Indexed Citations, EMBASE, Science Citation Index, Biosis, LILACS, Dissertation abstracts and National Technical Information Service from inception to 2018.MethodsRisk of bias and applicability was assessed using the QUADAS-2 tool. We performed random-effects logistic regression to meta-analyse studies grouped by reference standard.Results6 studies (341 patients) were included in this review. All studies were judged at high risk of bias. There was substantial heterogeneity across studies in sensitivity (range 57%–100%) and specificity (10%–86%) estimates. Four studies were diagnostic cohort studies that used either intraoperative findings during surgery (pooled sensitivity: 93.5% [95% CI 84.0 to 97.6]; specificity: 50.0% [16.8 to 83.2]) or ‘outcome following surgery’ as the reference standard (pooled sensitivity: 90.9% [83.1 to 95.3]; specificity 22.0% [7.4 to 49.9]). Two studies had a within-patient case-control study design, but results were not pooled because different types of control injections were used.ConclusionsWe found limited evidence which was of low methodological quality indicating that the diagnostic accuracy of SNRB is uncertain and that specificity in particular may be low. SNRB is a safe test with a low risk of clinically significant complications, but it remains unclear whether the additional diagnostic information it provides justifies the cost of the test.


2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Pakpoom Subsoontorn ◽  
Manupat Lohitnavy ◽  
Chuenjid Kongkaew

AbstractMany recent studies reported coronavirus point-of-care tests (POCTs) based on isothermal amplification. However, the performances of these tests have not been systematically evaluated. Cochrane Handbook for Systematic Reviews of Diagnostic Test Accuracy was used as a guideline for conducting this systematic review. We searched peer-reviewed and preprint articles in PubMed, BioRxiv and MedRxiv up to 28 September 2020 to identify studies that provide data to calculate sensitivity, specificity and diagnostic odds ratio (DOR). Quality Assessment of Diagnostic Accuracy Studies 2 (QUADAS-2) was applied for assessing quality of included studies and Preferred Reporting Items for a Systematic Review and Meta-analysis of Diagnostic Test Accuracy Studies (PRISMA-DTA) was followed for reporting. We included 81 studies from 65 research articles on POCTs of SARS, MERS and COVID-19. Most studies had high risk of patient selection and index test bias but low risk in other domains. Diagnostic specificities were high (> 0.95) for included studies while sensitivities varied depending on type of assays and sample used. Most studies (n = 51) used reverse transcription loop-mediated isothermal amplification (RT-LAMP) to diagnose coronaviruses. RT-LAMP of RNA purified from COVID-19 patient samples had pooled sensitivity at 0.94 (95% CI: 0.90–0.96). RT-LAMP of crude samples had substantially lower sensitivity at 0.78 (95% CI: 0.65–0.87). Abbott ID Now performance was similar to RT-LAMP of crude samples. Diagnostic performances by CRISPR and RT-LAMP on purified RNA were similar. Other diagnostic platforms including RT- recombinase assisted amplification (RT-RAA) and SAMBA-II also offered high sensitivity (> 0.95). Future studies should focus on the use of un-bias patient cohorts, double-blinded index test and detection assays that do not require RNA extraction.


2019 ◽  
Vol 57 (6) ◽  
Author(s):  
Emily MacLean ◽  
Giorgia Sulis ◽  
Claudia M. Denkinger ◽  
James C. Johnston ◽  
Madhukar Pai ◽  
...  

ABSTRACT Invasive collection methods are often required to obtain samples for the microbiological evaluation of children with presumptive pulmonary tuberculosis (PTB). Nucleic acid amplification testing of easier-to-collect stool samples could be a noninvasive method of diagnosing PTB. We conducted a systematic review and meta-analysis to evaluate the diagnostic accuracy of testing stool with the Xpert MTB/RIF assay (“stool Xpert”) for childhood PTB. Four databases were searched for publications from January 2008 to June 2018. Studies assessing the diagnostic accuracy among children of stool Xpert compared to a microbiological reference standard of conventional specimens tested by mycobacterial culture or Xpert were eligible. Bivariate random-effects meta-analyses were performed to calculate pooled sensitivity and specificity of stool Xpert against the reference standard. From 1,589 citations, 9 studies (n = 1,681) were included. Median participant ages ranged from 1.3 to 10.6 years. Protocols for stool processing and testing varied substantially, with differences in reagents and methods of homogenization and filtering. Against the microbiological reference standard, the pooled sensitivity and specificity of stool Xpert were 67% (95% confidence interval [CI], 52 to 79%) and 99% (95% CI, 98 to 99%), respectively. Sensitivity was higher among children with HIV (79% [95% CI, 68 to 87%] versus 60% [95% CI, 44 to 74%] among HIV-uninfected children). Heterogeneity was high. Data were insufficient for subgroup analyses among children under the age of 5 years, the most relevant target population. Stool Xpert could be a noninvasive method of ruling in PTB in children, particularly those with HIV. However, studies focused on children under 5 years of age are needed, and generalizability of the evidence is limited by the lack of standardized stool preparation and testing protocols.


2019 ◽  
Vol 57 (6) ◽  
Author(s):  
Ali Pormohammad ◽  
Mohammad Javad Nasiri ◽  
Timothy D. McHugh ◽  
Seyed Mohammad Riahi ◽  
Nathan C. Bahr

ABSTRACTThe diagnosis of tuberculous meningitis (TBM) is difficult and poses a significant challenge to physicians worldwide. Recently, nucleic acid amplification (NAA) tests have shown promise for the diagnosis of TBM, although their performance has been variable. We undertook a systematic review and meta-analysis to evaluate the diagnostic accuracy of NAA tests with cerebrospinal fluid (CSF) samples against that of culture as the reference standard or a combined reference standard (CRS) for TBM. We searched the Embase, PubMed, Web of Science, and Cochrane Library databases for the relevant records. The QUADAS-2 tool was used to assess the quality of the studies. Diagnostic accuracy measures (i.e., sensitivity and specificity) were pooled with a random-effects model. All statistical analyses were performed with STATA (version 14 IC; Stata Corporation, College Station, TX, USA), Meta-DiSc (version 1.4 for Windows; Cochrane Colloquium, Barcelona, Spain), and RevMan (version 5.3; The Nordic Cochrane Centre, the Cochrane Collaboration, Copenhagen, Denmark) software. Sixty-three studies comprising 1,381 cases of confirmed TBM and 5,712 non-TBM controls were included in the final analysis. These 63 studies were divided into two groups comprising 71 data sets (43 in-house tests and 28 commercial tests) that used culture as the reference standard and 24 data sets (21 in-house tests and 3 commercial tests) that used a CRS. Studies which used a culture reference standard had better pooled summary estimates than studies which used CRS. The overall pooled estimates of sensitivity, specificity, positive likelihood ratio (PLR), and negative likelihood ratio (NLR) of the NAA tests against culture were 82% (95% confidence interval [CI], 75 to 87%), 99% (95% CI, 98 to 99%), 58.6 (95% CI, 35.3 to 97.3), and 0.19 (95% CI, 0.14 to 0.25), respectively. The pooled sensitivity, specificity, PLR, and NLR of NAA tests against CRS were 68% (95% CI, 41 to 87%), 98% (95% CI, 95 to 99%), 36.5 (95% CI, 15.6 to 85.3), and 0.32 (95% CI, 0.15 to 0.70), respectively. The analysis has demonstrated that the diagnostic accuracy of NAA tests is currently insufficient for them to replace culture as a lone diagnostic test. NAA tests may be used in combination with culture due to the advantage of time to result and in scenarios where culture tests are not feasible. Further work to improve NAA tests would benefit from the availability of standardized reference standards and improvements to the methodology.


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.


2019 ◽  
Author(s):  
Choon Han Tan ◽  
Bhone Myint Kyaw ◽  
Helen Smith ◽  
Colin S Tan ◽  
Lorainne Tudor Car

BACKGROUND Diabetic retinopathy (DR), a common complication of diabetes mellitus, is the leading cause of impaired vision in adults worldwide. Smartphone ophthalmoscopy involves using a smartphone camera for digital retinal imaging. Utilizing smartphones to detect DR is potentially more affordable, accessible, and easier to use than conventional methods. OBJECTIVE This study aimed to determine the diagnostic accuracy of various smartphone ophthalmoscopy approaches for detecting DR in diabetic patients. METHODS We performed an electronic search on the Medical Literature Analysis and Retrieval System Online (MEDLINE), EMBASE, and Cochrane Library for literature published from January 2000 to November 2018. We included studies involving diabetic patients, which compared the diagnostic accuracy of smartphone ophthalmoscopy for detecting DR to an accurate or commonly employed reference standard, such as indirect ophthalmoscopy, slit-lamp biomicroscopy, and tabletop fundus photography. Two reviewers independently screened studies against the inclusion criteria, extracted data, and assessed the quality of included studies using the Quality Assessment of Diagnostic Accuracy Studies–2 tool, with disagreements resolved via consensus. Sensitivity and specificity were pooled using the random effects model. A summary receiver operating characteristic (SROC) curve was constructed. This review is reported in line with the Preferred Reporting Items for a Systematic Review and Meta-analysis of Diagnostic Test Accuracy Studies guidelines. RESULTS In all, nine studies involving 1430 participants were included. Most studies were of high quality, except one study with limited applicability because of its reference standard. The pooled sensitivity and specificity for detecting any DR was 87% (95% CI 74%-94%) and 94% (95% CI 81%-98%); mild nonproliferative DR (NPDR) was 39% (95% CI 10%-79%) and 95% (95% CI 91%-98%); moderate NPDR was 71% (95% CI 57%-81%) and 95% (95% CI 88%-98%); severe NPDR was 80% (95% CI 49%-94%) and 97% (95% CI 88%-99%); proliferative DR (PDR) was 92% (95% CI 79%-97%) and 99% (95% CI 96%-99%); diabetic macular edema was 79% (95% CI 63%-89%) and 93% (95% CI 82%-97%); and referral-warranted DR was 91% (95% CI 86%-94%) and 89% (95% CI 56%-98%). The area under SROC curve ranged from 0.879 to 0.979. The diagnostic odds ratio ranged from 11.3 to 1225. CONCLUSIONS We found heterogeneous evidence showing that smartphone ophthalmoscopy performs well in detecting DR. The diagnostic accuracy for PDR was highest. Future studies should standardize reference criteria and classification criteria and evaluate other available forms of smartphone ophthalmoscopy in primary care settings.


2018 ◽  
Vol 159 (2) ◽  
pp. 220-230 ◽  
Author(s):  
Elizabeth A. Kelly ◽  
Bin Li ◽  
Meredith E. Adams

Objective (1) To determine the diagnostic accuracy of tuning fork tests (TFTs; Weber and Rinne) for assessment of hearing loss as compared with standard audiometry. (2) To identify the audiometric threshold at which TFTs transition from normal to abnormal, thus indicating the presence of hearing loss. Data Sources PubMed, Ovid Medline, EMBASE, Web of Science, Cochrane, and Scopus and manual bibliographic searches. Review Methods A systematic review of studies reporting TFT accuracy was performed according to a standardized protocol. Two independent evaluators corroborated the extracted data and assessed risk of bias. Results Seventeen studies with 3158 participants, including adults and children, met inclusion criteria. The sensitivity and specificity of the Rinne test for detecting conductive hearing loss ranged from 43% to 91% and 50% to 100%, respectively, for a 256-Hz fork and from 16% to 87% and 55% to 100% for a 512-Hz fork. The audiometric thresholds at which tests transition from normal to abnormal ranged from 13 to 40 dB of conductive hearing loss for the Rinne test and from 2.5 to 4 dB of asymmetry for the Weber test. Significant heterogeneity in TFT methods and audiometric thresholds to define hearing loss precluded meta-analysis. There is high risk of bias in patient selection for a majority of the studies. Conclusion Variability exists in the reported test accuracy measurements of TFTs for clinical screening, surgical candidacy assessments, and estimation of hearing loss severity. Clinicians should remain mindful of these differences and optimize these techniques in specific clinical applications to improve TFT accuracy.


PM&R ◽  
2013 ◽  
Vol 5 (10) ◽  
pp. 856-881 ◽  
Author(s):  
Theresa L.-B. Pape ◽  
Walter M. High ◽  
Justin St. Andre ◽  
Charlesnika Evans ◽  
Bridget Smith ◽  
...  

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