AMA warns of limitations of serological testing

The FDA is handing out emergency use authorizations (EUAs) like candy in an attempt to get tests, therapeutics, and vaccines to market at record speed in order to help fight the Covid-19 pandemic, but there is a downside — EUA products are not subject to the same scrutiny that products that eventually earn FDA approval undergo, which means it is not surprising that safety and efficacy issues emerge with increasing usage.

Abbott Laboratories’ ID NOW COVID-19 is a case in point. This test, which President Donald Trump heralded as “a whole new ballgame“, and which is used to test the president and government staffers, appears to miss nearly half of all Covid-19 cases, according to a not-yet peer-reviewed study from NYU Langone Health, New York.

The researchers tested Abbott’s Covid-19 test against Cepheid’s GeneXpert. The researchers noted that, at their NYU lab, they use two RT-PCR tests — Roche’s Cobas and Cepheid’s GeneXpert. “Both platforms perform comparably with similar limits of detection (LOD) of SARS-CoV-2 viral RNA, 100-150 and 250 copies/mL, respectively,” the study authors wrote. But these tests take time — 3.5 hours and 45 minutes, respectively, and the researchers were interested in comparing accuracy of the rapid test to these tried and true tests.

ID NOW, which “uses isothermal nucleic acid amplification of the RdRp viral target with acclaimed LOD of 125 copies/mL,” promises delivery of test results in as little as 5 minutes, the researchers wrote.

Compared to the Cepheid using swabs stored in stabilizing solution, Abbott’s test missed a third of the positive samples, and compared with collecting samples using a dry swab, the Abbott product missed 48% of the positive cases.

As its shares began to tumble on the news, Abbott questioned the study’s methodology. However, this response is notable given that on April 22, Abbott did warns that its tests are prone to false positives, especially if a collection site uses a transport or stabilizing media for the swabs with the nasal samples, instead of placing them directly in the machine. But, while this might explain the 33% missed Covid-19 cases, it does not explain the nearly 50% of missed cases collected by dry swabs and placed into the machine per the NYU study.

The NYU results will likely be closely followed, particularly because of the highly public use of the ID NOW test by the White House and the assurances that the tests of the president, vice president, and others in the executive branch are indeed negative.

Meanwhile, the American Medical Association (AMA) is warning the public on the limitations of serological (antibody) testing and has issued guidance to help convey these limitations.

Again, noting the rapidity with which these products are coming on the market, clinicians and the public cannot assume that, if antibodies are found, that they confer immunity to Covid-19, and the AMA “warns that public health decisions, such as discontinuation of physical distancing, should not be made on the basis of results.”

“Given that we do not yet have scientific evidence showing if, when, and for how long individuals might become immune to Covid-19, physicians and the general public should not use antibody testing to consider anyone immune to the disease—doing so may lead individuals to falsely assume they can stop physical distancing and further the spread of illness,” said AMA President Patrice A. Harris, MD, MA, said in a statement. “Although many are using these tests to determine whether an individual had Covid-19, we encourage physicians to only use antibody tests authorized by the Food and Drug Administration (FDA) and only for the purposes of population-level studies, evaluating recovered individuals for convalescent plasma donations, or along with other clinical information as part of a well-defined testing plan for groups or individuals.”

Underscoring one of the problems that follows products hitting the market after EUAs are given, the AMA noted that “the FDA does not automatically independently verify performance of each of these tests and primarily relies on submitting manufacturers to self-validate their offerings. For tests that are not commercially marketed, such as laboratory developed tests, FDA authorization is not required. However, these tests must be performed in a laboratory certified to perform high-complexity testing under CLIA.”

The physician organization noted that, as of May 5, twelve commercial serological tests have been granted EUAs, and there are more than 120 tests on the market.

“Recently, concern has been growing over both test performance and fraudulent labeling of a number of currently marketed tests,” the AMA said in its guidance.

The public and clinicians needs to be aware that these tests can produce false positive results and be prone to cross-reactivity, where more than one virus is found, the AMA noted.

Candace Hoffmann, Managing Editor, BreakingMED™

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