Dive Brief:

• Abbott Laboratories' Panbio rapid antigen test misses half of COVID-19 cases in asymptomatic people, according to a study run by the Irish healthcare system.

• The finding, which is in line with the results of a U.K. study of a rival test sold by Innova, led Ireland's Health Service Executive to recommend against using single, standalone antigen kits for the purposes of asymptomatic screening.

• HSE also assessed rapid antigen tests from companies including Abbott, LumiraDx and Roche in symptomatic patients, concluding that variation in the performance of the kits means they should not be considered interchangeable.

Dive Insight:

HSE carried out the study to assess whether rapid antigen tests have a role to play in the detection of COVID-19 in acute hospitals, meat processing plants and community swabbing centers. The study assessed the use of seven rapid antigen products to test symptomatic people and one kit to evaluate asymptomatic individuals. Ireland accessed the Panbio test used in the asymptomatic portion of the study under a European Union tender. 

The assessment of asymptomatic individuals took place in meat processing plants, which have been the sources of COVID-19 outbreaks around the world. HSE found that using the Abbott test to analyze self-collected nasal swabs detected 41 of the 79 cases picked up by PCR, resulting in a sensitivity of 51.9%. Panbio has a CE mark for asymptomatic screening and self-swabbing. 

Advocates of antigen testing, including Abbott, have argued the approach mainly misses people who have low viral loads and are therefore unlikely to be infectious. In a CDC study, the sensitivity of Abbott's BinaxNOW antigen test in asymptomatic people rose from 35.8% in the overall population to 78.6% in individuals whose samples could be cultured.

HSE, however, thinks it is important to detect individuals with low viral loads, stating that "people can be seriously ill and can be infectious or be about to become infectious, even when the virus is only detectable at low levels."

Nonetheless, the health service removed people with low viral loads from the analysis by limiting the dataset to people whose samples yielded positive results after 25 or 30 PCR cycles, also known as threshold cycle (Ct). The analysis did not change HSE's position. 

"Our data indicates that there remains a risk of missing a substantial proportion of potentially infectious cases, including 20% of those with Ct ≤25 and 31% of those with Ct ≤30. Therefore, use of this assay in settings such as testing of asymptomatic high-risk populations is not recommended as a standalone test," the health service wrote in its report.

The study did not assess the effects of performing frequent repeat testing every two to three days in conjunction with confirmatory PCR. However, with the European Centre for Disease Prevention and Control proposing the approach, HSE said rapid antigen kits could potentially be used in such a testing regimen.

The other part of the study evaluated multiple antigen tests in symptomatic people. With an overall sensitivity of 95%, MyBio's MoLab mö-screen Corona Antigen Test performed best, although all the results have wide, overlapping confidence intervals that prevent the definitive ranking of the kits.

In general, nasopharyngeal samples resulted in higher sensitivities than nasal swabs.

All the sensitivity results generated by HSE fell short of the manufacturer claimed data but still typically cleared the 80% minimum threshold proposed by the World Health Organization.

Other groups have also failed to replicate the sensitivities claimed by the manufacturer. In the U.K., the divergence between the results claimed by Innova, the subject of a FDA warning letter last week, and the data generated in the real world has contributed to a call by the Royal Statistical Society to change the licensing process for diagnostic tests.