BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and the resulting COVID-19 pandemic present important diagnostic challenges. Several diagnostic strategies are available to identify or rule out current infection, identify people in need of care escalation, or to test for past infection and immune response. Point-of-care antigen and molecular tests to detect current SARS-CoV-2 infection have the potential to allow earlier detection and isolation of confirmed cases compared to laboratory-based diagnostic methods, with the aim of reducing household and community transmission.
OBJECTIVES: To assess the diagnostic accuracy of point-of-care antigen and molecular-based tests to determine if a person presenting in the community or in primary or secondary care has current SARS-CoV-2 infection.
SEARCH METHODS: On 25 May 2020 we undertook electronic searches in the Cochrane COVID-19 Study Register and the COVID-19 Living Evidence Database from the University of Bern, which is updated daily with published articles from PubMed and Embase and with preprints from medRxiv and bioRxiv. In addition, we checked repositories of COVID-19 publications. We did not apply any language restrictions.
SELECTION CRITERIA: We included studies of people with suspected current SARS-CoV-2 infection, known to have, or not to have SARS-CoV-2 infection, or where tests were used to screen for infection. We included test accuracy studies of any design that evaluated antigen or molecular tests suitable for a point-of-care setting (minimal equipment, sample preparation, and biosafety requirements, with results available within two hours of sample collection). We included all reference standards to define the presence or absence of SARS-CoV-2 (including reverse transcription polymerase chain reaction (RT-PCR) tests and established clinical diagnostic criteria).
DATA COLLECTION AND ANALYSIS: Two review authors independently screened studies and resolved any disagreements by discussion with a third review author. One review author independently extracted study characteristics, which were checked by a second review author. Two review authors independently extracted 2x2 contingency table data and assessed risk of bias and applicability of the studies using the QUADAS-2 tool. We present sensitivity and specificity, with 95% confidence intervals (CIs), for each test using paired forest plots. We pooled data using the bivariate hierarchical model separately for antigen and molecular-based tests, with simplifications when few studies were available. We tabulated available data by test manufacturer.
MAIN RESULTS: We included 22 publications reporting on a total of 18 study cohorts with 3198 unique samples, of which 1775 had confirmed SARS-CoV-2 infection. Ten studies took place in North America, two in South America, four in Europe, one in China and one was conducted internationally. We identified data for eight commercial tests (four antigen and four molecular) and one in-house antigen test. Five of the studies included were only available as preprints. We did not find any studies at low risk of bias for all quality domains and had concerns about applicability of results across all studies. We judged patient selection to be at high risk of bias in 50% of the studies because of deliberate over-sampling of samples with confirmed COVID-19 infection and unclear in seven out of 18 studies because of poor reporting. Sixteen (89%) studies used only a single, negative RT-PCR to confirm the absence of COVID-19 infection, risking missing infection. There was a lack of information on blinding of index test (n = 11), and around participant exclusions from analyses (n = 10). We did not observe differences in methodological quality between antigen and molecular test evaluations. Antigen tests Sensitivity varied considerably across studies (from 0% to 94%): the average sensitivity was 56.2% (95% CI 29.5 to 79.8%) and average specificity was 99.5% (95% CI 98.1% to 99.9%; based on 8 evaluations in 5 studies on 943 samples). Data for individual antigen tests were limited with no more than two studies for any test. Rapid molecular assays Sensitivity showed less variation compared to antigen tests (from 68% to 100%), average sensitivity was 95.2% (95% CI 86.7% to 98.3%) and specificity 98.9% (95% CI 97.3% to 99.5%) based on 13 evaluations in 11 studies of on 2255 samples. Predicted values based on a hypothetical cohort of 1000 people with suspected COVID-19 infection (with a prevalence of 10%) result in 105 positive test results including 10 false positives (positive predictive value 90%), and 895 negative results including 5 false negatives (negative predictive value 99%). Individual tests We calculated pooled results of individual tests for ID NOW (Abbott Laboratories) (5 evaluations) and Xpert Xpress (Cepheid Inc) (6 evaluations). Summary sensitivity for the Xpert Xpress assay (99.4%, 95% CI 98.0% to 99.8%) was 22.6 (95% CI 18.8 to 26.3) percentage points higher than that of ID NOW (76.8%, (95% CI 72.9% to 80.3%), whilst the specificity of Xpert Xpress (96.8%, 95% CI 90.6% to 99.0%) was marginally lower than ID NOW (99.6%, 95% CI 98.4% to 99.9%; a difference of -2.8% (95% CI -6.4 to 0.8)) AUTHORS' CONCLUSIONS: This review identifies early-stage evaluations of point-of-care tests for detecting SARS-CoV-2 infection, largely based on remnant laboratory samples. The findings currently have limited applicability, as we are uncertain whether tests will perform in the same way in clinical practice, and according to symptoms of COVID-19, duration of symptoms, or in asymptomatic people. Rapid tests have the potential to be used to inform triage of RT-PCR use, allowing earlier detection of those testing positive, but the evidence currently is not strong enough to determine how useful they are in clinical practice. Prospective and comparative evaluations of rapid tests for COVID-19 infection in clinically relevant settings are urgently needed. Studies should recruit consecutive series of eligible participants, including both those presenting for testing due to symptoms and asymptomatic people who may have come into contact with confirmed cases. Studies should clearly describe symptomatic status and document time from symptom onset or time since exposure. Point-of-care tests must be conducted on samples according to manufacturer instructions for use and be conducted at the point of care. Any future research study report should conform to the Standards for Reporting of Diagnostic Accuracy (STARD) guideline.
As front-line providers facing an impending influenza season amidst a COVID-19 pandemic that waxes and wanes regionally, emergency medicine must understand the diagnostic accuracy and reliability of currently available COVID-19 rapid tests in conjunction with history/physical exam. Unfortunately, this Cochrane review is limited by the overall poor-quality evidence currently available. Furthermore, the strict Cochrane reporting methods limit the user-friendliness of this systematic review as the authors neglect to name the subtypes of bias and associated skew in observed accuracy (http://pmid.us/24238322) or the potential etiologies of false negatives (http://pmid.us/32542934).
This is a meta-analysis of rapid tests for COVID-19 compared with criterion standard tests (polymerase chain reaction or established clinical diagnostic criteria). The search for studies was sufficiently exhaustive and the overall risk of bias in the included studies was low (average of one-third for the five criteria evaluated). All tests had good positive likelihood ratios (LRs). For the six antigen tests and two rapid molecular tests (IDnew and XpertXpress), these were 112 (mean result of the six tests), 192 and 31, respectively. The corresponding negative LRs were 0.44 (mean result of the six tests), 0.23 and 0.006, making the XpertXpress test the most useful since it is best able to rule out disease when the test is negative.
This comprehensive and timely review of testing for COVID is useful for all clinicians that may need to test or interpret testing for patients with COVID. The rapid antigen test has a sensitivity that is too low for comfort. The cepheid rapid test (PCR) has better operating characteristics than the Abbot. Supply chain issues will most likely guide choice of test kit, but awareness of local prevalence and these test characteristics are needed to help interpret and guide clinical decision-making.
This has limited clinical applicability as it is still in the very early stages of antigen testing, so the literature reflects this dearth of knowledge. Will be more important as the evidence base increases.
bottomline: (as expected) ...the evidence is very weak... further studies are needed... This is not very useful.
This paper finds there is substantial variability in sensitivity among COVID tests; although, specificity remains good (91.5%). This is of enormous concern in public health and for whether to discontinue isolation among other decisions. The proportion of false-negatives remains higher than it should for its common use.
This Cochrane review follows typical methodology, and identifies testing characteristics for tests that have published results. They found that rapid tests compared favourably to PCR, with a number of concerns, including tests being done not according to protocol, population selection, and poor reporting. In general, the authors indicated that these tests may "have the potential to select people for RT-PCR testing or be used where RT-PCR is not available", but that "evidence currently is not strong enough... to be used in practice".
The information in this review is interesting but the relevance for clinical practice is not very high.
A Cohrane review of the current state of testing for infection with SARS CoV-2 that reviewed multiple tests. Unfortunately, there was a high risk for bias in many studies. Several were written by employees of the companies that produced the testing. Also, the "gold standard" for comparison was PCR testing that was often only performed once, which has a significant false-negative risk depending on timing and sample collection.
Current antigen point-of-care testing is not sensitive enough to be useful for SARS-CoV-2 testing, but rapid molecular assays show some promise. However, their performance in purely clinical testing vs laboratory environment will need further testing.
Almost everything related to the COVID pandemic changes rapidly, which happened in this paper.
The review demonstrates the need for more studies from Asia and Africa.
Rapid tests for COVID-19 will simplify decision making and patient management. Until the tests have been adequately studied for reliability, they remain something for the future. This article tells us they are not ready for routine clinical use.