Methodological problems of SARS-CoV-2 rapid point-of-care tests when used in mass testing

Abstract

The aim of the current study is to perform model calculations on the possible use of SARS-CoV-2-rapid point-of-care tests as mass tests, using the quality criteria extracted from evidence-based research as an example for the Federal Republic of Germany. In addition to illustrating the problem of false positive test results, these calculations are used to examine their possible influence on the 7-day incidence. For a substantial period of time, this parameter formed the decisive basis for decisions on measures to protect the population in the wake of the COVID pandemic, which were taken by the government. Primarily, model calculations were performed for a base model of 1,000,000 SARS-CoV-2-rapid point-of-care tests per week using various sensitivities and specificities reported in the literature, followed by sequential testing of the test positives obtained by a SARS-CoV-2 PCR test. Furthermore, a calculation was performed for an actual maximum model based on self-test contingents by the German Federal Ministry of Health. Assuming a number of 1,000,000 tests per week at a prevalence of 0.5%, a high number of false positive test results, a low positive predictive value, a high negative predictive value, and an increase in the 7-day incidence due to the additional antigen rapid tests of approx. 5/100,000 were obtained. A previous maximum calculation based on contingent numbers for self-tests given by the German Federal Ministry of Health even showed an additional possible influence on the 7-day incidence of 84.6/100,000. The model calculations refer in each case to representative population samples that would have to be drawn if the successive results were comparable which should be given, as far-reaching actions were based on this parameter. The additionally performed SARS-CoV-2-rapid point-of-care tests increase the 7-day incidence in a clear way depending on the number of tests and clearly show their dependence on the respective number of tests. SARS-CoV-2-rapid point-of-care tests as well as the SARS-CoV-2-PCR test method should both be used exclusively in the presence of corresponding respiratory symptoms and not in symptom-free persons.

Keywords: COVID-19; SARS-CoV-2; methodology; point-of-care diagnostics; rapid testing.

Figure 1.. Simulation calculation for the Hotgen antigen rapid test with sequential testing strategy and prevalence of 0.5%.

Figure 2.. Simulation calculation for the PCR post-testing of the positive test results of the Hotgen antigen rapid test from Figure 1 with a pre-test probability of 35.52%.

Figure 3.. Number of false positive test results after rapid antigen testing and after subsequent SARS-CoV-2 PCR testing with the data from the respective studies in the results section. These were extrapolated to 1,000,000 tests per week and 0.5% prevalence. Only the calculation for the German Federal Ministry of Health (Bundesministerium für Gesundheit, BGM, English abbreviation: FMH) data was carried out with 16.5 million tests. The results related BGM (FMH) can be converted into the figures of the Robert-Koch-Institute by dividing them by 16.5 because they are based on the same statistical quality criteria.

Figure 4.. Positive predictive value (PPV) after rapid antigen testing with the data from the respective studies in the results section. These were transferred to 1,000,000 tests per week and 0.5% prevalence. Only the calculation for the German Federal Ministry of Health (Bundesministerium für Gesundheit, BGM, English abbreviation: FMH) data was carried out with 16.5 million tests.