SARS-CoV-2 serology tests: 3 big limitations doctors must understand

Kevin B. O'Reilly , Senior News Editor

What’s the news: Results from the SARS-CoV-2 serology tests that have flooded the market should not be used to make decisions by individuals, such as whether to end physical distancing.

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That warning is part of new guidance from the AMA on serological testing for SARS-CoV-2 antibodies that outlines three major limitations to the tests that physicians must understand to properly order them and interpret their 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.

“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.”

Serology tests also have inherent limitations, including a significant risk of false-positive results when disease prevalence is low, Dr. Harris said. Read more about the FDA’s new SARS-CoV-2 antibody test rules.

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Why it’s important: Much discussion has focused on the potential use of SARS-CoV-2 serology testing to develop so-called immunity passports or to ease the physical distancing countermeasures that are limiting the deadly spread of COVID-19.

The FDA is now requiring all commercial test manufacturers to apply for an emergency use authorization to offer their tests on the market. The FDA has also provided recommended performance criteria for these tests. Physicians should pay close attention to the regulatory status of any test offered. FDA maintains a listing of all serological tests authorized for use for COVID-19.

Doctors and patients must understand that these serological tests for SARS-CoV-2 antibodies are especially difficult to interpret because so much remains unknown about immune status for this novel coronavirus. Here are three major limitations physicians should know about.

False-positive results. Serological testing for disease with a low prevalence in the population presents inherent challenges with interpretation of positive results. Even high-performing tests—that is, those are highly specific and sensitive—will return false-positive results when disease prevalence is low, as is now the case with COVID-19.

Cross-reactivity. While this may not be true of all serology tests for SARS-CoV-2, cross-reactivity has been a noted concern among some offered tests. This happens when a test for antibodies for SARS-CoV-2 identifies not only antibodies for this virus, but also for other coronaviruses, such as those causing the common cold.

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Immune status. According to the World Health Organization, there is no current evidence showing immunity to COVID-19 after infection. While individuals typically develop some type of immune response after exposure to most viruses, it is not yet clear when an immune response develops after COVID-19 infection, how strong this immune response may be, and how long the immune response may last.

Use of serology tests should currently be limited to population-level seroprevalance study, evaluation of recovered individuals for convalescent plasma donations, or as part of a well-defined testing plan in concert with other clinical information by physicians well-versed in interpretation of serology test results.

Dive deeper into the AMA’s new guidance to learn more about these limitations and why physicians shouldn’t use serology tests to determine immune status or as the sole basis for diagnosing COVID-19.

Learn more: Stay up to speed on the AMA’s COVID-19 advocacy efforts and track the fast-moving pandemic with the AMA's COVID-19 resource center, which offers a library of the most up-to-date resources from JAMA Network™, the Centers for Disease Control and Prevention, and the WHO.