Rapid antigen test: Don’t let perfect be the enemy of good

Pearl Toh
23 Oct 2021
Rapid antigen test: Don’t let perfect be the enemy of good

While rapid antigen test is less sensitive than conventional nucleic acid amplification test (NAAT) such as RT-PCR* in detecting SARS-CoV-2 virus, “a test does not have to be perfect to be clinically useful,” said Professor Angela Caliendo during a session in IDWeek 2021 — echoing the maxim that perfect should not be the enemy of good in the pandemic era.

“Rapid isothermal NAAT or antigen test are acceptable testing options when rapid RT-PCR or standard laboratory-based NAAT are not readily available, or results will be delayed beyond 2–3 days,” said Caliendo, a leading expert in diagnostics from the Warren Alpert Medical School of Brown University in Providence, Rhode Island, US.

“You can certainly use these test if there is an issue with availability of [conventional] NAAT, or NAAT turnaround time is going to be too slow to be clinically meaningful,” she stated.

“Antigen test have a very high specificity. So you won’t see issues around false positive results,” Caliendo highlighted.

As she explained, sensitivity of antigen testing is equivalent in both symptomatic adults and children, regardless of whether the results were read using an instrument or manually, or it was done through direct testing or with a transport media involved.

Hit early, hit right

“For optimal performance, antigen tests should be used within 7 days of symptom onset,” Caliendo stressed.

“If clinical suspicion for COVID-19 remains high, negative antigen results should be confirmed by a standard NAAT,” she added.

Being highlighted was a prospective study comparing the BinaxNOW antigen test to RT-PCR and viral culture on 532 paired specimens obtained from 234 residents and staff in a nursing home. During early infection, the positive percent agreement (PPA) of the BinaxNOW antigen test hit as high as 86 percent and 95 percent, compared with RT-PCR and virus culture, respectively. However, the antigen test performance declined when used in late infection, with a PPA of 51 percent and no recovered virus, respectively. [Ann Intern Med 2021;174:945-951]

“Early and frequent antigen testing during an outbreak can effectively identify infectious people with the greatest potential to transmit the virus — [which] allows for rapid isolation and cohorting,” Caliendo pointed out.

BinaxNOW antigen test is the sister test to Panbio Rapid Antigen Test that is focused on the US market, while the latter is authorized for use in the European market but not in the US. Both used the same biologics but come in different formats: BinaxNow as a card while Panbio is a small cassette.

Complementary testing

The role of rapid antigen testing to supplement RT-PCR to detect COVID-19 outbreak in a workplace was further elucidated in a study on 342 horse racetrack workers (median age 52 years). [IDWeek 2021, abstract P366]

Based on 769 paired samples collected, BinaxNOW showed a PPA of 43.3 percent, negative percent agreement (NPA) of 100 percent, and positive predictive value (PPV) of 100 percent, compared with RT-PCR results.

“High NPA and PPV support immediate isolation of BinaxNOW-positive individuals, while low PPA supports confirmatory testing following BinaxNOW-negative results,” explained the researchers.

Among the 127 specimens tested positive on RT-PCR, those which also tested positive on BinaxNOW (n=55) were samples with a lower mean Ct value (17.8 vs 28.5; p<0.001) compared with samples with paired BinaxNOW-negative results (n=72).

“BinaxNOW performed better in paired specimens with lower Ct value and positive viral cultures, which could suggest that among RT-PCR-positive specimens, those that are BinaxNOW-negative may be less likely to contain infectious virus than those that are BinaxNOW-positive,” noted the researchers.

Frequent testing ups sensitivity

Citing a longitudinal study comparing the diagnostic performance of RT-PCR, antigen testing, and viral cultures in 43 adults, Caliendo noted that the sensitivity of antigen test increased with serial testing for multiple times per week, using RT-PCR as a reference. [J Infect Dis 2021;224:976-982]

“If you test every day for a period of 14 days, all three tests will ultimately detect those who are infectious. Results from testing every other day or every three days [are still] reliable. After that, the sensitivity of antigen testing starts to drop off [with longer intervals between tests],” explained Caliendo, as she walked through the findings.

“It appears that if you test frequently with a less sensitive test, you are actually going to get a reasonable ability to identify the people who are culture positive,” she summed up.


*RT-PCR: reverse transcription-polymerase chain reaction

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