Molecular, antigen tests have their own pros and cons
Molecular tests and antigen tests have characteristics that make them ideal — and sometimes not so ideal — in the clinical setting, a speaker at the Infectious Diseases in Children Symposium said.
Gregory A. Storch, MD, a professor of pediatrics at Washington University School of Medicine in St. Louis, used three different diseases to illustrate his point.
He said reverse transcriptase PCR (RT-PCR) for COVID-19 has a high level of sensitivity when administered correctly and can be included in multiplex panels. However, the test can also yield false-negative results.
“This is in part related to the sample that's being used,” he said. “If the person obtaining the [nasal pharyngeal] sample isn't skilled at it, isn't well trained or doesn't do a good job, then that can obviously affect the sensitivity of the testing.”
RT-PCR also can cause what Storch called “prolonged positivity” of COVID-19.
“These tests can be positive for many weeks after [a] person is first infected, but that positivity does not correlate with active infection,” he explained. “We don't judge a person's infectiousness based on these tests. We also do not generally recommend doing follow-up RT-PCR tests after a person has had a negative result.”
Storch noted that, in the office, clinicians now have access to CLIA-waived molecular tests — “a remarkable thing” — and a new generation of antigen tests with an optical reader that are more sensitive than traditional rapid tests while remaining less expensive than molecular tests.
The rationale for using molecular or new generation antigen tests instead of a traditional antigen test for diagnosing influenza is largely based on numbers. A traditional antigen test for influenza A has sensitivity of 61.2% and a specificity of 99.2%. These rates are 87.6% and 98.1%, respectively, for the new generation antigen tests and 90.2% and 99%, respectively, for rapid molecular tests.
COVID-19 and influenza “overlap in symptoms,” Storch said. “This is why we really have to do testing, because our clinical judgment is not adequate to know who has COVID, influenza or some other respiratory syndrome.”
Molecular testing for group A Streptococcus addresses concerns regarding the commonly used Centor Score, he continued, noting that even the highest “modified” of these scores showed only about half the patients had the disease. Molecular test results take approximately 45 minutes to obtain and antigen tests take about 15 minutes, whereas the traditional culture test takes between 18 and 48 hours to provide results, Storch said. Molecular tests have a sensitivity of 97%, greater than the 85% sensitivity of antigen tests and 90% sensitivity of culture tests.
However, with the molecular test’s high level of sensitivity for group A Streptococcus comes at least one drawback, according to Storch.
“This leads to a potential problem that the test will detect colonization and ... we may overdiagnose group A,” he said.