Evaluation of “Rapid” Antibody Test in Britain Suggests High Number of False Positives

Accuracy of test may be influenced by size of population to be screened and prevalence of COVID-19 within that population.

Like most of the world, Britain is in the midst of some of the darkest days of the COVID-19 pandemic.

As of Sunday, the nation—which includes England, Scotland, Wales, and Northern Ireland—1.53 million total cases and more than 55000 deaths. Collectively, the “home countries,” as they are called, are reporting than 18000 cases per day.

If this seems to pale in comparison to the ongoing crisis in the United States, keep in mind that Britain, with 66.65 million people has about 1/5th the population of the US.

Lost among the positive news surrounding vaccines against SARS-CoV-2, the virus that causes COVID-19, have been some promising results with new testing technologies. And, as in the case with the hunt for a new vaccine, researchers in Britain have taken a leadership role in efforts to develop enhanced—both in terms of speed and accuracy—diagnostics.

However, an analysis published on November 11 by The BMJ, for example, showcases a testing platform created by the so-called UK Rapid Test Consortium (UK-RTC) called the “AbC-19 Rapid Test” (AbC-19)—and indicates there is room for improvement, given a high number of false positives.

For the new analysis, the researchers, affiliated with Public Health England, assessed the test, which contains trimeric SARS-CoV-2 S protein attached to a membrane that when recognized by IgG antibodies causes the formation of a band visible to the test-taker, with 2,847 key workers—including healthcare staff, fire and rescue personnel, and police officers—in England in June. Among the study participants, 268 had a previous polymerase chain reaction (PCR) positive test result for COVID-19 within the previous 2 to 3 months, while the remaining 2,579 had unknown prior infection status). In addition, samples collected from 1,995 pre-pandemic blood donors served as controls.

According to the researchers, test result bands were “often weak,” with positive/negative discordance by 3 trained laboratory staff for roughly 4% of the devices. Using consensus readings, sensitivity and specificity for known positive and negative samples was 92.5% and 97.9%, respectively. Using an immunoassay reference standard, sensitivity was 94.2% among PCR-confirmed cases but 84.7% among other participants with SARS-CoV-2 antibodies. If 1 million key workers were tested with AbC-19 and 10% had actually been previously infected, the researchers estimated that there would be 84,700 true positive and 18,900 false positive results, meaning the probability that a positive result was correct would be 81.7%.

Their findings differ from those of a previous analysis, performed at Ulster University, which is not yet peer reviewed. That earlier study found a sensitivity of 97.7% and specificity of 100%—suggesting no false positives.

“If the AbC-19 test were to be used for mass population screening in a relatively low prevalence setting, we would anticipate a large number of false positive results,” wrote the researchers, who did not respond to requests for comment. “Consequently, AbC-19 test positives would need to be checked with a confirmatory assay, a practice followed in HIV and syphilis serodiagnosis, if such an assay for SARS-CoV-2 could be shown to be sufficiently specific for this purpose.”

They added, “if people were to use and read the test themselves, rather than the test being read by trained laboratory technicians, or if a digital reader were developed, the accuracy of the test as read using these alternative approaches would need to be evaluated.”