COVID-19 Testing – Impact of Prevalence, Sensitivity, and Specificity on Patient Risk and Cost (original) (raw)
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Identifying the SARS-CoV-2 virus has been a unique challenge for the scientific community. In this paper, we discuss a practical solution to help guide clinicians with interpretation of the probability that a positive, or negative, COVID-19 test result indicates an infected person, based on their clinical estimate of pre-test probability of infection.The authors conducted a small survey on LinkedIn to confirm that hypothesis that that the clinical pre-test probability of COVID-19 increases relative to local prevalence of disease plus patient age, known contact, and severity of symptoms. We examined results of PPA (Positive Percent Agreement, sensitivity) and NPA (Negative Percent Agreement, specificity) from 73 individual laboratory experiments for molecular tests for SARS-CoV-2 as reported to the FIND database 1, and for selected methods in FDA EUA submissions2,3. Authors calculated likelihood ratios to convert pre-test to post-test probability of disease and designed an online cal...
International Journal of Infectious Diseases, 2021
Background: Commercial availability of serological tests to evaluate immunoglobulins (Ig) targeting severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has grown exponentially since the start of the coronavirus disease 2019 (COVID-19) outbreak. Thorough validation of these tests is important before use as epidemiological tools to infer seroprevalence in specific populations and as diagnostic tools to complement molecular approaches (e.g., quantitative reverse transcription-polymerase chain reaction). Methods: Commercial serological tests from 11 suppliers were assayed side-by-side using 126 samples from SARS-CoV-2-infected inpatients and 36 from healthy and HIV-infected individuals. Results: The majority of the tests assayed have >95% specificity. For the sensitivity calculation, samples were stratified by days since symptoms onset; sensitivity peaks at 16-21 days for IgM and IgA (maximum 91.2%, Euroimmun) and, dependant on the test, at 16-21 or >21 days for IgG (maximum 94.1%, Snibe). Data from semiquantitative tests show that patients with a severe clinical presentation have lower levels of Ig targeting SARS-CoV-2 at <10 days since symptoms onset and higher levels at >21 days, compared to patients with a non-severe presentation. Conclusions: This study highlights the heterogeneity of sensitivity and generally high specificity of the serological tests and establishes a basis for their usefulness to complement diagnostic techniques and population seroprevalence studies.
Diagnostics
Background: We assessed the sensitivity, specificity and positive and negative predictive value (PPV and NPV) of molecular and serological tests for the diagnosis of SARS-CoV-2 infection. Methods: A total of 346 patients were enrolled in the emergency room. We evaluated three Reverse Transcriptase-real time PCRs (RT-PCRs) including six different gene targets, five serologic rapid diagnostic tests (RDT) and one ELISA. The final classification of infected/non-infected patients was performed using Latent Class Analysis combined with clinical re-assessment of incongruous cases. Results: Out of these, 24.6% of patients were classified as infected. The molecular test RQ-SARS-nCoV-2 showed the highest performance with 91.8% sensitivity, 100% specificity, 100.0% PPV and 97.4% NPV respectively. Considering the single gene targets, S and RdRp of RQ-SARS-nCoV-2 had the highest sensitivity (94.1%). The in-house RdRp presented the lowest sensitivity (62.4%). The specificity ranged from 99.2% for...
Clinical Performance of SARS-CoV-2 Molecular Testing
2020
Molecular testing for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the gold standard for diagnosis of coronavirus disease 2019 (COVID-19), but the test clinical performance is poorly understood. From 3/10/2020-5/1/2020 NewYork-Presbyterian laboratories performed 27,377 SARS-CoV-2 molecular assays from 22,338 patients. Repeat testing was performed in 3,432 patients, of which 2,413 had negative and 1,019 had positive first day results. Repeat-tested patients were more likely to be older, male, African-American or Hispanic, and to have severe disease. Among the patients with initially negative results, 18.6% became positive upon repeat-testing. Only 58.1% of any-time positive patients had a result of "detected" on the first test. The clinical sensitivity of COVID-19 molecular assays is estimated between 66.2% and 95.6%, depending on the unknown number of false negative results in single-tested patients. Conversion to a negative result is unlikely to occur b...
2020
ABSTRACTCommercial availability of serological tests to evaluate immunoglobulins (Ig) towards severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has grown exponentially since the onset of COVID-19 (Coronavirus Disease 2019) outbreak. Their thorough validation is of extreme importance before using them as epidemiological tools to infer population seroprevalence, and as complementary diagnostic tools to molecular approaches (e.g. RT-qPCR). Here we assayed commercial serological tests (semiquantitative and qualitative) from 11 suppliers in 126 samples collected from hospitalized COVID-19 patients, and from 36 healthy and HIV-infected individuals (collected at the pre-COVID-19 pandemic). Specificity was above 95% in 9 tests. Samples from COVID-19 patients were stratified by days since symptoms onset (<10, 10-15, 16-21 and >21 days). Tests sensitivity increases with time since symptoms onset, and peaks at 16-21 days for IgM and IgA (maximum: 91.2%); and from 16-21 to >...
COVID-19 Serological Tests: How Well Do They Actually Perform?
In only a few months after initial discovery in Wuhan, China, SARS-CoV-2 and the associated COVID-19 disease has become a global pandemic causing significant mortality and morbidity. In the absence of vaccines and effective therapeutics, reliable serological testing can be a key element of public health policy to control further spread of the disease and gradually ease quarantine measures. However, prior to launch of large-scale seroprevalence studies to assess herd immunity, it is critical to understand the limits and potential of current SARS-CoV-2 serological tests on the market. In this study, we provide an overview of serological testing and conduct a systematic review of independent evaluations of SARS-CoV-2 serological tests performance. Our findings show significant variability in the accuracy of marketed tests and highlight several lab-based and point-of-care rapid diagnostic tests with high performance level in detecting SRAS-CoV-2 specific antibodies. The findings of this...
Disease Prevalence Matters: Challenge for SARS-CoV-2 Testing
Antibodies
While sensitivity and specificity are important characteristics for any diagnostic test, the influence of prevalence is equally, if not more, important when such tests are used in community screening. We review the concepts of positive/negative predictive values (PPV/NPV) and how disease prevalence affects false positive/negative rates. In low-prevalence situations, the PPV decreases drastically. We demonstrate how using two tests in an orthogonal fashion can be especially beneficial in low-prevalence settings and greatly improve the PPV of the diagnostic test results.
2021
ObjectiveTo investigate the performance of a rapid point-of-care antibody test, the BioMedomics COVID-19 IgM/IgG Rapid Test, in comparison with a high-quality, validated, laboratory-based platform, the Roche Elecsys Anti-SARS-CoV-2 assay.MethodsSerological testing was conducted on 708 individuals. Concordance metrics were estimated. Logistic regression was used to assess associations with seropositivity.ResultsSARS-CoV-2 seroprevalence was 63.4% (449/708; 95% CI 59.8%-66.9%) using the BioMedomics assay and 71.9% (509/708; 95% CI 68.5%-75.1%) using the Elecsys assay. There were 62 discordant results between the two assays. One specimen was seropositive in the BioMedomics assay, but seronegative in the Elecsys assay, while 61 specimens were seropositive in the Elecsys assay, but seronegative in the BioMedomics assay. Positive, negative, and overall percent agreements between the two assays were 88.0% (95% CI 84.9%-90.6%), 99.5% (95% CI 97.2%-99.9%), and 91.2% (95% CI 88.9%-93.1%), res...
Balance of Risk in COVID-19 Reveals the Extreme Cost of False Positives
International Journal of Vaccine Theory, Practice, and Research
COVID-19 public health responses, including lockdowns and diagnostic testing strategies, have had consequences. Economic costs (see the CHD paper in this issue) could reach $16 trillion dollars, 90% of the US annual GDP. While harm to small businesses, unemployment, worsening poverty, death from cancer, increased suicides, social isolation, and restriction of freedom all increase the perceived need for drastic responses from the top, flawed measures are costly. A diagnostic assay[1] of tests for COVID-19 depends for its validity on its sensitivity and specificity assessed in terms of the true positive rate (TPR), false positive rate (FPR), true negative rate (TNR), and false negative rate (FNR) of the assays. In this pandemic, Real Time — Polymerase Chain Reaction (RT-PCR) testing has been relied on for drastic top-down responses (as in shutting down the economy of whole nations or the entire world). Here I focus on false positive results where RT-PCR testing suggests many infection...