Performance of SARS-CoV-2 Antigen Assays

It is important for healthcare providers and testing professionals to understand the performance characteristics of the antigen test used, including sensitivity, specificity, and positive and negative predictive value, and to follow the manufacturer's instructions for use, which summarize performance characteristics.The “gold standard” of clinical diagnostic testing for SARS-CoV-2 remains the laboratory-based (moderate and high complexity) NAAT.Therefore, providers may choose to use a laboratory-based NAAT to confirm antigen test results, especially if the results of the antigen test are inconsistent with the clinical situation.The clinical performance of NAAT and antigen tests may differ from clinical utility when considering issues such as test availability, quality of specimen collection and shipment, and turnaround time for results.Depending on their directions for use,some point-of-care NAATs may not be available for confirmatory testing.NAATs that produce presumptive results are not suitable for confirmatory testing.Antigen levels in specimens collected before the onset of symptoms or later in the course of infection may be below the detection limit of the test,resulting in false negative antigen test results, while more sensitive tests, such as most NAATs, may return a positive result.Antigen testing has comparable sensitivity to lab-based NAAT when the viral load in the specimen is high and the person is likely to be most infectious, study shows.The specificity of the antigen test is comparable to that of the NAAT, which means that false positive test results are less likely if the antigen test is used according to the manufacturer's instructions.Despite the high specificity of antigen testing, false-positive results can still occur, especially when used in settings where the probability or prevalence of infection prior to testing is low-a situation that applies to all in vitro diagnostic tests.In general, for all diagnostic tests, the lower the prevalence of community infection, the higher the proportion of false positive test results. 

The positive and negative predictive values of all in vitro diagnostic tests (e.g.NAAT and antigen tests) vary by pretest probability.The pre-test probability takes into account the prevalence of the target infection in the tested population as well as the clinical background of the tested individual.The pretest probability is generally considered high if the prevalence of infection in the community is high, the person tested is symptomatic, and the likelihood of an alternative diagnosis is low.If the community infection rate is low and the person tested is asymptomatic and has not had close contact with a person with COVID-19, the pretest probability is generally considered low. State health departments routinely release COVID-19 data on their community case rates.For more information on the relationship between pretest probability and likelihood of positive and negative predictive value, see CDC's Diagnostic Test Interpretation Results.

Processing of SARS-CoV-2 Antigen Tests

The conditions of authorization in the antigen EUA specify that CLIA-certified laboratories and testing sites should follow the manufacturer's instructions for use, usually found in the package insert, when performing the test and reading test results.Authorized use instructions for each test,including when and how to read each test, can also be found in FDA's In Vitro Diagnostics EUA. All testing for SARS-CoV-2, including antigen testing, depends on sample integrity, which is affected by sample collection and handling procedures.Quality assurance procedures should be followed to prevent cross-contamination and inaccurate test results For more information on proper specimen handling and handling for COVID-19 testing, including point-of-care testing, see CDC Guidance for Point-of-Care Testing and Interim Laboratory Biosafety Guidance for Specimen Handling and Handling Related to COVID-19 (COVID-19).

Interpreting SARS-CoV-2 Antigen Test Results

Interpretation of the results of a SARS-CoV-2 antigen test depends primarily on the clinical and epidemiological background of the person being tested (eg, symptoms, close contact with other COVID-19 patients, environment where they live, likelihood of infection) Alternative diagnosis,or disease prevalence in their geographic location).For more details on testing recommendations.In evaluating the results of SARS-CoV-2 antigen tests, performance characteristics (e.g., sensitivity, specificity) and instructions for use of FDA-authorized tests, and the prevalence of SARS-CoV-2 infection in the community (in the community relative to population size number of cases) should be considered.The evaluation of antigen test results should also consider whether the person is symptomatic, and if so, how long the symptoms last.Typically, healthcare providers can rely on positive antigen test results in symptomatic patients because of the high specificity of current FDA-authorized antigen tests.The sensitivity of currently FDA-authorized antigen tests varies, so negative diagnostic test results should be handled on a case-by-case basis.In most cases, the manufacturer's instructions for the use of the antigen test indicate that negative test results should be considered "presumptive," meaning they are preliminary results. See FDA's In Vitro Diagnostics EUA.It may be appropriate to use a laboratory-based NAAT to confirm antigen test results.For confirmatory testing, CDC recommends the use of a laboratory-based NAAT that has been evaluated for analytical sensitivity against an FDA reference panel NAATs that produce presumptive results are not suitable for confirmatory testing.

CDC has developed a community testing algorithm for people who do not live in congregate settings.The main purpose of the test is to reduce the spread of SARS-CoV-2 in the community, where there is concern about introduction and widespread spread, by rapidly identifying and isolating infected individuals.Additional guidance has been developed for those living in congregate settings.Proper case identification is especially important in these settings,where false positive test results can have significant consequences because isolated individuals need to be clustered together or in close proximity, long-term care facilities, correctional and detention facilities, homeless and other group shelters, and higher education shared housing settings.