Clinical Pearls & Morning Reports
Published January 19, 2022
As of December 2021, the FDA had granted emergency use authorization (EUA) status to 28 rapid diagnostic tests (RDTs) for the diagnosis of acute SARS-CoV-2 infection, and more FDA-authorized tests are expected. Read the NEJM Clinical Practice Article here.
Q: What are the two types of RDTs for SARS-CoV-2?
A: RDTs that are authorized by the FDA to diagnose SARS-CoV-2 infection are either nucleic acid amplification tests (NAATs) to detect genes or antigen-based immunoassays to detect proteins of SARS-CoV-2. The molecular and antigen-based RDTs with EUA status have various pathogen targets, detection methods, swabbing sites to obtain specimens, indications for use, and performance characteristics. Although both techniques are highly specific, NAATs are generally more sensitive than antigen-based tests because they amplify target genomic sequences.
Q: When should an RDT be performed in an asymptomatic person with a known exposure to SARS-CoV-2?
A: In persons with exposure to SARS-CoV-2, testing is generally not useful in the first 48 hours after exposure, since the virus will not have achieved a sufficient viral load. The most appropriate window for testing is generally considered to be 5 to 7 days after exposure, which is the average peak of symptoms and viral load. For a two-test strategy, which is the FDA-approved indication for most RDTs for asymptomatic screening, a second RDT should be performed 2 days after a negative test.
A: The appropriate interpretation of RDTs for SARS-CoV-2 testing and screening depends on the clinical indication and the pretest probability of infection. Among persons with a moderate-to-high pretest probability, which includes symptomatic persons and asymptomatic persons who have had close contact with a person with Covid-19, a positive RDT indicates a confirmed SARS-CoV-2 infection. However, RDTs may have false negative results, and repeat testing should be considered in cases of high clinical suspicion or worsening symptoms and in the serial screening of asymptomatic persons. A second negative RDT 2 days after the initial test or a negative laboratory-based NAAT would help to rule out SARS-CoV-2 infection. In persons with a low pretest probability of infection (e.g., asymptomatic persons without a known SARS-CoV-2 exposure), a single negative RDT provides reassurance that SARS-CoV-2 infection is unlikely. However, given imperfect specificity, a positive RDT may indicate a false positive result. In persons with low pretest probability of infection who have a positive RDT, a confirmatory test should be performed promptly.
A: Although some RDTs appear to perform well in the detection of major viral variants, most field-based validation studies were conducted before the emergence of the delta and omicron variants. New viral mutations may directly alter the genomic sequence that is detected by molecular RDTs, and the FDA recently issued warnings about two molecular tests that are not expected to detect the omicron variant. Since antigen-based RDTs detect epitopes on the surface proteins (mostly nucleocapsid), their performance is more dependent on protein structure and confirmation than on single genomic mutations. Nonetheless, clinical studies are urgently needed to evaluate the performance of molecular and antigen-based RDTs, including saliva-based tests, in detecting emerging variants of concern. Studies are also needed to evaluate the performance of these tests with respect to breakthrough infections among vaccinated persons (with or without booster vaccination).