For diagnostic (viral) tests, it is important to note the following:
The “gold standard” for clinical diagnostic detection of SARS-CoV-2 remains laboratory-based molecular tests (NAATs, RT-PCR). Therefore, it may be necessary to confirm an antigen test result with a laboratory-based NAAT, especially if the result of the antigen test is inconsistent with the clinical context.
The sensitivity of antigen tests varies but is generally lower than most molecular-based NAATs. This may lead to a false-negative result because the antigen level in specimens collected either before symptom onset or late in the course of infection, may be below the tests’ limit of detection. This can result in a negative antigen test result, while a more sensitive test, such as most NAATs, may return a positive result. On the other hand, antigen tests have been shown to have comparable sensitivity to molecular-based NAATs when the viral load in the specimen is high and the individual is likely to be most contagious.
The specificity of antigen tests is generally as high as most NAATs, which indicates that false-positive test results are unlikely when an antigen test is properly used. Despite the high specificity of antigen tests, false-positive results will occur, especially when used in communities where the prevalence of infection is low. In general, it can be noted that for all diagnostic tests, the lower the prevalence of infection in the community, the higher the proportion of false-positive test results.
Positive and negative predictive values of all diagnostic (viral) tests (e.g., NAAT and antigen tests) vary depending upon the pretest situation. If the prevalence of infection in the community is high and the person being tested is symptomatic, then the pretest probability for a positive test result is considered high. If the prevalence of infection in the community is low and the person being tested is asymptomatic and has not had known contact with a person with COVID-19, then the pretest probability is considered low.
Proper interpretation of both molecular and antigen test results is important for accurate clinical management of patients or individuals with suspected COVID-19, or for the identification of infected people when used for screening settings.
