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AACC Panel Provides Guidelines on Validation, Use of SARS-CoV-2 Serology Tests

NEW YORK – A panel of experts from the American Association for Clinical Chemistry has released a set of practical recommendations for clinical labs developing and offering SARS-CoV-2 serology tests.

Published on Wednesday in Clinical Chemistry, the guidelines address the various uses for serology testing and which tests are most appropriate for which specific applications, as well as verification and validation processes for these assays.

Antibody tests were initially seen as a potentially important tool that would allow public health researchers to track SARS-CoV-2 infections and monitor the prevalence of the virus in various communities. More recently, interest has grown in using these tests to assess the response of individuals to vaccines against the virus.

Muddled messaging and regulatory mistakes have limited the usefulness of these tests, however, as government officials and others began promoting them for uses — including the identification of people who had recovered from COVID-19 infection — for which they were poorly suited, and decisions by the US Food and Drug Administration opened the market to a flood of low-performing tests.

The AACC authors noted, as well, that the limitations of the FDA's EUA process along with the large number of available tests, their "varied performance characteristics," and the field's "incomplete understand of the humoral immune response in COVID-19," had left many labs with questions as to "how to best utilize and interpret" serology tests.

While several professional organizations published interim guidelines for these tests, there was not a guidance providing "comprehensive and practical recommendations for the selection, validation, implementation, and quality management of EUA or laboratory developed test (LDT) serologic tests," the AACC authors wrote, explaining the thinking behind the development of their recommendations.

The guidelines cover requirements under CLIA for verification for FDA-approved or cleared assays and EUA assays as well as validation of LDT serology tests. They also address ongoing considerations such as implementation for quality control practices and interpretation of serology test results in the context of the performance of a particular test in a specific target population and the impact infection prevalence can have on test accuracy.

With the rollout of vaccines, serology testing to assess patient immune response is currently of particular interest to many, and the AACC guidelines address questions around this use, noting that while serology testing can determine if an individual has developed antibodies in response to vaccination, thresholds for what level of antibody response indicates vaccine efficacy have not been determined for any serology assays, and therefore these test "should not be used to determine vaccine efficacy and protective immunity."

This echoes recent statements from Tim Stenzel, director of the FDA's Office of In Vitro Diagnostics and Radiological Health, who noted the agency has seen cases where clinicians have ordered serology testing for vaccinated patients and received negative results.

"When investigations have been done, it turns out that that vaccine generates an antibody to a spike protein, but the serology test is directed toward the N protein. So, that serology test is obviously not going to be the ideal candidate for clinicians to order an off-label test to take a look at a response to vaccine," he said.

While serology testing "can play important functions in the management of SARS-CoV-2 infection and the pandemic," labs "should recognize the utility and limitations of serology tests, and carefully select and implement EUA or LDT assays and interpret test results," the AACC authors wrote.