Analysis of the specificity of a COVID-19 antigen test in the Slovak mass testing program

Abstract

Aims Mass antigen testing programs have been challenged because of an alleged insufficient specificity, leading to a large number of false positives. The objective of this study is to derive a lower bound of the specificity of the SD Biosensor Standard Q Ag-Test in large scale practical use. Methods Based on county data from the nationwide tests for SARS-CoV-2 in Slovakia between 31.10.–1.11. 2020 we calculate a lower confidence bound for the specificity. As positive test results were not systematically verified by PCR tests, we base the lower bound on a worst case assumption, assuming all positives to be false positives. Results 3,625,332 persons from 79 counties were tested. The lowest positivity rate was observed in the county of Rožňava where 100 out of 34307 (0.29%) tests were positive. This implies a test specificity of at least 99.6% (97.5% one-sided lower confidence bound, adjusted for multiplicity). Conclusion The obtained lower bound suggests a higher specificity compared to earlier studies in spite of the underlying worst case assumption and the application in a mass testing setting. The actual specificity is expected to exceed 99.6% if the prevalence in the respective regions was non-negligible at the time of testing. To our knowledge, this estimate constitutes the first bound obtained from large scale practical use of an antigen test.

Spatial scales, patterns, and positivity trends of SARS-CoV-2 pandemics in mass rapid antigen testing in Slovakia

“…Also note that the vertical intercept of the weighted linear regression to the reduced dataset of the counties with small antigen test positivity (< 1%) ( S1 Table , not shown in figure) provides a rough estimate of specificity of the antigen tests used (99.55–99.57%), since it represents the predicted (false) positivity at zero RT-qPCR incidence (0.43–0.45%). These values are in agreement with the manufacturer provided information and with additional validation studies (see Appendix A in S1 Text ) and close to the minimum test specificity estimate in [ 29 ] that uses the same data set.…”

“…The results of the mass rapid antigen testing in Slovakia were also studied elsewhere [14][15][16]29]. Unlike the other studies we primarily study spatial patterns and use the fine-resolved municipalities positivity data instead of coarsened county data used elsewhere.…”

“…See Appendix A in S1 Text for a survey of test validation studies with sensitivity median 71.6% and average 72.1%, and specificity median 99.3% and average 98.6%. The lower bound for test specificity in mass testing in Slovakia was estimated at 99.6% in [ 29 ]. Mass testing methodology and setup are described in detail in [ 14 , 15 ], see also Appendix B in S1 Text .…”

Avoiding false positive SARS-CoV-2 rapid antigen test results with point-of-care molecular testing on residual test buffer

“…Consistent with our previous study 11 , false positive Ag-RDTs were described as having barely visible target bands, with antigen scores +/- or 1+. The proportion of false positives observed (10/3676 or 0.3%) is consistent with manufacturer and literature claims, where false positive reactions are rare at approximately 0.4% 18,19 .…”

Use of Rapid Antigen Tests during the Omicron Wave

“…4 In light of the results of our meta-analysis (Figure 1) and the likely increase in sensitivity of rapid antigen tests to detect infectious Omicron cases when using a combined oral-nasal sample, we assume a sensitivity of 60% for rapid antigen tests when using a combined sample, and a specificity of 99.5%. [18][19][20] We therefore estimate a positive likelihood ratio of 0.60/(1-0.995) = 120, indicating that a positive test is highly predictive of an infectious case when using a combined oral-nasal sample.…”