Dataset Information

The estimation of diagnostic accuracy of tests for COVID-19: A scoping review.

ABSTRACT:

Objectives

To assess the methodologies used in the estimation of diagnostic accuracy of SARS-CoV-2 real-time reverse transcription polymerase chain reaction (rRT-PCR) and other nucleic acid amplification tests (NAATs) and to evaluate the quality and reliability of the studies employing those methods.

Methods

We conducted a systematic search of English-language articles published December 31, 2019-June 19, 2020. Studies of any design that performed tests on ≥10 patients and reported or inferred correlative statistics were included. Studies were evaluated using elements of the Quality Assessment of Diagnostic Accuracy Studies (QUADAS-2) guidelines.

Results

We conducted a narrative and tabular synthesis of studies organized by their reference standard strategy or comparative agreement method, resulting in six categorizations. Critical study details were frequently unreported, including the mechanism for patient/sample selection and researcher blinding to results, which lead to concern for bias.

Conclusions

Current studies estimating test performance characteristics have imperfect study design and statistical methods for the estimation of test performance characteristics of SARS-CoV-2 tests. The included studies employ heterogeneous methods and overall have an increased risk of bias. Employing standardized guidelines for study designs and statistical methods will improve the process for developing and validating rRT-PCR and NAAT for the diagnosis of COVID-19.

SUBMITTER: Axell-House DB

PROVIDER: S-EPMC7457918 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:ObjectiveTo determine the diagnostic accuracy of serological tests for coronavirus disease-2019 (covid-19).DesignSystematic review and meta-analysis.Data sourcesMedline, bioRxiv, and medRxiv from 1 January to 30 April 2020, using subject headings or subheadings combined with text words for the concepts of covid-19 and serological tests for covid-19.Eligibility criteria and data analysisEligible studies measured sensitivity or specificity, or both of a covid-19 serological test compared with a reference standard of viral culture or reverse transcriptase polymerase chain reaction. Studies were excluded with fewer than five participants or samples. Risk of bias was assessed using quality assessment of diagnostic accuracy studies 2 (QUADAS-2). Pooled sensitivity and specificity were estimated using random effects bivariate meta-analyses.Main outcome measuresThe primary outcome was overall sensitivity and specificity, stratified by method of serological testing (enzyme linked immunosorbent assays (ELISAs), lateral flow immunoassays (LFIAs), or chemiluminescent immunoassays (CLIAs)) and immunoglobulin class (IgG, IgM, or both). Secondary outcomes were stratum specific sensitivity and specificity within subgroups defined by study or participant characteristics, including time since symptom onset.Results5016 references were identified and 40 studies included. 49 risk of bias assessments were carried out (one for each population and method evaluated). High risk of patient selection bias was found in 98% (48/49) of assessments and high or unclear risk of bias from performance or interpretation of the serological test in 73% (36/49). Only 10% (4/40) of studies included outpatients. Only two studies evaluated tests at the point of care. For each method of testing, pooled sensitivity and specificity were not associated with the immunoglobulin class measured. The pooled sensitivity of ELISAs measuring IgG or IgM was 84.3% (95% confidence interval 75.6% to 90.9%), of LFIAs was 66.0% (49.3% to 79.3%), and of CLIAs was 97.8% (46.2% to 100%). In all analyses, pooled sensitivity was lower for LFIAs, the potential point-of-care method. Pooled specificities ranged from 96.6% to 99.7%. Of the samples used for estimating specificity, 83% (10 465/12 547) were from populations tested before the epidemic or not suspected of having covid-19. Among LFIAs, pooled sensitivity of commercial kits (65.0%, 49.0% to 78.2%) was lower than that of non-commercial tests (88.2%, 83.6% to 91.3%). Heterogeneity was seen in all analyses. Sensitivity was higher at least three weeks after symptom onset (ranging from 69.9% to 98.9%) compared with within the first week (from 13.4% to 50.3%).ConclusionHigher quality clinical studies assessing the diagnostic accuracy of serological tests for covid-19 are urgently needed. Currently, available evidence does not support the continued use of existing point-of-care serological tests.Study registrationPROSPERO CRD42020179452.

Project description:ObjectiveSevere acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged as a global pandemic in early 2020 with rapidly evolving approaches to diagnosing the clinical illness called coronavirus disease (COVID-19). The primary objective of this scoping review is to synthesize current research of the diagnostic accuracy of history, physical examination, routine laboratory tests, real-time reverse transcription-polymerase chain reaction (rRT-PCR), immunology tests, and computed tomography (CT) for the emergency department (ED) diagnosis of COVID-19. Secondary objectives included a synopsis of diagnostic biases likely with current COVID-19 research as well as corresponding implications of false-negative and false-positive results for clinicians and investigators.MethodsA Preferred Reporting Items for Systematic Reviews and Meta-Analyses-Scoping Review (PRISMA-ScR)-adherent synthesis of COVID-19 diagnostic accuracy through May 5, 2020, was conducted. The search strategy was designed by a medical librarian and included studies indexed by PubMed and Embase since January 2020.ResultsA total of 1,907 citations were screened for relevance. Patients without COVID-19 are rarely reported, so specificity and likelihood ratios were generally unavailable. Fever is the most common finding, while hyposmia and hypogeusia appear useful to rule in COVID-19. Cough is not consistently present. Lymphopenia is the mostly commonly reported laboratory abnormality and occurs in over 50% of COVID-19 patients. rRT-PCR is currently considered the COVID-19 criterion standard for most diagnostic studies, but a single test sensitivity ranges from 60% to 78%. Multiple reasons for false-negatives rRT-PCR exist, including sample site tested and disease stage during which sample was obtained. CT may increase COVID-19 sensitivity in conjunction with rRT-PCR, but guidelines for imaging patients most likely to benefit are emerging. IgM and IgG serology levels are undetectable in the first week of COVID-19, but sensitivity (range = 82% to 100%) and specificity (range = 87% to 100%) are promising. Whether detectable COVID-19 antibodies correspond to immunity remains unanswered. Current studies do not adhere to accepted diagnostic accuracy reporting standards and likely report significantly biased results if the same tests were to be applied to general ED populations with suspected COVID-19.ConclusionsWith the exception of fever and disorders of smell/taste, history and physical examination findings are unhelpful to distinguish COVID-19 from other infectious conditions that mimic SARS-CoV-2 like influenza. Routine laboratory tests are also nondiagnostic, although lymphopenia is a common finding and other abnormalities may predict severe disease. Although rRT-PCR is the current criterion standard, more inclusive consensus-based criteria will likely emerge because of the high false-negative rate of PCR tests. The role of serology and CT in ED assessments remains undefined.

Project description:ObjectiveTo determine the diagnostic accuracy of serological tests for coronavirus disease-2019 (COVID-19).MethodsPubMed, Embase and the Cochrane Library were searched from January 1 2020 to September 2 2022. We included studies that measured the sensitivity, specificity or both qualities of a COVID-19 serological test and a reference standard of a viral culture or reverse transcriptase polymerase chain reaction (RT-PCR). The risk of bias was assessed by using quality assessment of diagnostic accuracy studies 2 (QUADAS-2). The primary outcomes included overall sensitivity and specificity, as stratified by the methods of serological testing [enzyme-linked immunosorbent assays (ELISAs), lateral flow immunoassays (LFIAs) or chemiluminescent immunoassays (CLIAs)] and immunoglobulin classes (IgG, IgM, or both). Secondary outcomes were stratum-specific sensitivity and specificity within the subgroups, as defined by study or participant characteristics, which included the time from the onset of symptoms, testing via commercial kits or an in-house assay, antigen target, clinical setting, serological kit as the index test and the type of specimen for the RT-PCR reference test.ResultsEight thousand seven hundred and eighty-five references were identified and 169 studies included. Overall, we judged the risk of bias to be high in 47.9 % (81/169) of the studies, and a low risk of applicability concerns was found in 100% (169/169) of the studies. For each method of testing, the pooled sensitivity of the ELISAs ranged from 81 to 82%, with sensitivities ranging from 69 to 70% for the LFIAs and 77% to 79% for the CLIAs. Among the evaluated tests, IgG (80-81%)-based tests exhibited better sensitivities than IgM-based tests (66-68%). IgG/IgM-based CLIA had the highest sensitivity [87% (86-88%)]. All of the tests displayed high specificity (97-98%). Heterogeneity was observed in all of the analyses. The detection of nucleocapsid protein (77-80%) as the antigen target was found to offer higher sensitivity results than surface protein detection (66-68%). Sensitivity was higher in the in-house assays (78-79%) than in the commercial kits (47-48%).ConclusionAmong the evaluated tests, ELISA and CLIA tests performed better in terms of sensitivity than did the LFIA. IgG-based tests had higher sensitivity than IgM-based tests, and combined IgG/IgM test-based CLIA tests had the best overall diagnostic test accuracy. The type of sample, serological kit and timing of use of the specific tests were associated with the diagnostic accuracy. Due to the limitations of the serological tests, other techniques should be quickly approved to provide guidance for the correct diagnosis of COVID-19.

Project description:Antigen detection rapid diagnostic tests (Ag-RDTs) used for detecting severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) nucleocapsid protein are inexpensive, faster and easy to use alternative of Nucleic Acid Amplification Test (NAAT) for diagnosis of Coronavirus disease 2019 (COVID-19). In this systematic review and meta-analysis, we assessed the diagnostic accuracy of Ag-RDTs in low and middle-income countries (LMICs). We included studies that evaluated the diagnostic accuracy of Ag-RDTs (sensitivity and specificity) against reverse transcription-polymerase chain reaction (RT-PCR) as a reference standard. The study population comprised of people living in LMICs irrespective of age and gender, who had undergone testing for COVID-19. We included peer reviewed prospective or retrospective cohort studies, cross-sectional studies, case control studies, randomized clinical trials (RCTs) as well as non-randomized experimental studies which addressed the review question. A systematic search was conducted in PubMed, CINAHL, Embase, Scopus, and Google Scholar to identify studies published between 1 January, 2020 and 15 August, 2021. The Quality Assessment of Diagnostic Accuracy Studies (QUADAS)-2 tool was used to assess the methodological quality of studies. The analysis was done using Review Manager 5.4 and R software 4.0.2. From the total of 12 diagnostic accuracy studies with 4,817 study participants, pooled sensitivity and specificity were 78.2% and 99.5% respectively. Sensitivity was marginally higher in subgroup analysis based on studies with low risk of bias and applicability concerns (78.9%) and studies using SD Biosensor Ag-RDT (79.4%). However, an inverse relation between cycle threshold (Ct) and sensitivity of Ag-RDT was not seen. The review demonstrated pooled sensitivity value approaching the minimum performance requirement for diagnosis of COVID-19 by WHO with specificity value meeting the specified requirement. Ag-RDTs, therefore have the potential to be used as a screening tool for SARS-CoV-2 detection in low resource settings where RT-PCR might not be readily accessible. However, false negative results need to be interpreted with caution.

Project description:ObjectivesTo review evaluations of the diagnostic accuracy of coronavirus disease 2019 (COVID-19) rapid antigen tests (RATs) approved by the Therapeutic Goods Administration (TGA) for self-testing by ambulatory people in Australia; to compare these estimates with values reported by test manufacturers.Study designSystematic review of publications in any language that reported cross-sectional, case-control, or cohort studies in which the participants were ambulatory people in the community or health care workers in hospitals in whom severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection was suspected, and the results of testing self-collected biological samples with a TGA-approved COVID-19 RAT were compared with those of reverse transcription-polymerase chain reaction (RT-PCR) testing for SARS-CoV-2. Estimates of diagnostic accuracy (sensitivity, specificity) were checked and compared with manufacturer estimates published on the TGA website.Data sourcesPublications (to 1 September 2022) identified in the Cochrane COVID-19 Study Register and the World Health Organization COVID-19 research database. Information on manufacturer diagnostic accuracy evaluations was obtained from the TGA website.Data synthesisTwelve publications that reported a total of eighteen evaluations of eight RATs approved by the TGA for self-testing (manufacturers: All Test, Roche, Flowflex, MP Biomedicals, Clungene, Panbio, V-Chek, Whistling) were identified. Five studies were undertaken in the Netherlands, two each in Germany and the United States, and one each in Denmark, Belgium, and Canada; test sample collection was unsupervised in twelve studies, and supervised by health care workers or researchers in six. Estimated sensitivity with unsupervised sample collection ranged from 20.9% (MP Biomedicals) to 74.3% (Roche), and with supervised collection from 7.7% (V-Chek) to 84.4% (Panbio); the estimates were between 8.2 and 88 percentage points lower than the values reported by the manufacturers. Test specificity was high for all RATs (97.9-100%).ConclusionsThe risk of false negative results when using COVID-19 RATs for self-testing may be considerably higher than apparent in manufacturer reports on the TGA website, with implications for the reliability of these tests for ruling out infection.