New Guidelines Aim to Improve Use of SARS-CoV-2 (COVID-19) Antibody Tests
Following questions about the accuracy of tests for antibodies against SARS-CoV-2 (the virus that causes COVID-19), and possible misuse and misinterpretation of those tests, the U.S. Centers for Disease Control and Prevention (CDC) in May released interim (temporary) guidelines for their use.
News outlets have reported on the inaccurate results from some commercially available SARS-CoV-2 antibody tests and on the general misunderstanding by both the public and healthcare providers about what information this testing can provide.
SARS-CoV-2 antibody tests, often called serology tests, detect antibodies against SARS CoV-2 in the blood, which suggests an immune response to infection that will develop even in people who have not had symptoms of COVID-19. However, the presence of antibodies does not indicate whether an individual has active disease, nor whether there is any protective immunity against re-infection. Serology tests are distinct from diagnostic PCR tests, which find genetic material from SARS-CoV-2 in nasal and throat swabs. Antibody tests are not used to diagnose COVID-19 infection. (For more details on why, see the article on Coronavirus (COVID-19) Testing).
Correct Use and Interpretation
Serology tests provide a positive (reactive, antibodies detected) or a negative (non-reactive, antibodies not detected) result for the presence or absence of antibodies to SARS-CoV-2. Studies show that these antibodies most commonly become detectable about 1 to 3 weeks after symptom onset. At that point, it is possible that infectiousness has decreased. It is also possible that some degree of immunity from future infection may have developed, but the evidence for this is not yet conclusive.
The CDC’s guidelines warn against assuming that people with a positive antibody test result are protected from future infection. Additional data is needed before changing any public health recommendations about physical distancing and use of personal protective equipment based on serologic test results. The guidelines emphasize that antibody results should not be used to make decisions about admitting and grouping people in schools, dormitories, and correctional facilities, or returning to the workplace.
However, SARS-CoV-2 antibody tests can help determine the proportion of a population previously infected with the virus and provide information about which communities and populations may have experienced a higher infection rate. In some instances, serologic test results may help determine who may qualify to donate blood that can be used as part of the national COVID-19 convalescent plasma therapy clinical trials. Antibody tests may also be used as an aid for the diagnosis of COVID-19 for patients who present later on in their disease course (about 9 to 14 days after onset of symptoms) and are negative by the PCR test. A positive antibody result in these patients, alongside symptoms consistent with COVID-19, may help to confirm the diagnosis.
Quality Tests and Testing Strategies
The guidelines stress the importance of minimizing inaccurate antibody test results, particularly false positives (results that incorrectly identify a person as having antibodies and having been infected, when they have not). This may be accomplished using a few different strategies.
The guidelines recommend using serology tests that have been proven to correctly exclude individuals without SARS-CoV-2 antibodies (high specificity) and correctly identify those who do have antibodies (high sensitivity).
CDC’s guidelines note that the Food and Drug Administration (FDA) in May began requiring that antibody tests sold by diagnostic companies undergo independent review and obtain an emergency use authorization (EUA). This policy is a change from March, when the FDA permitted the use of tests before they were granted an EUA and while they were still under review. The FDA now requires manufacturers to submit validation data for EUA that show the tests meet defined specificity and sensitivity thresholds to ensure accuracy of the tests.
Even when using tests with high sensitivity and specificity, the guidelines recommend testing populations and individuals with an elevated likelihood of previous exposure to COVID-19. This increases the probability that a positive result is a true positive. Conversely, testing people in areas where the number of COVID-19 cases is low increases the chances of false positives because the likelihood of finding a person who has been infected is low.
In populations with low numbers of COVID-19 cases, an appropriate strategy may be to use two antibody tests instead of just one. If an initial antibody test is positive, a second, different antibody test can be used to confirm the initial results. For example, tests done at the point of care (POC) generally are not as accurate as tests performed in laboratories, so a positive POC test may be followed by a second antibody test performed in a lab to confirm the result.
In a recent article about its updated policy, the FDA noted that some people may need two antibody tests, as the CDC interim guidelines suggest. Even a high-performing antibody test’s accuracy can suffer when used on people who live in areas without COVID-19 infections, according to Anand Shah, M.D., FDA’s Deputy Commissioner for Medical and Scientific Affairs, and Jeff Shuren, M.D., Director of FDA’s Center for Devices and Radiological Health. “That is why antibody tests should only be used as part of a well-conceived testing plan and why the results should always be interpreted by appropriate experts,” they write.
Steve Eder, Megan Twohey and Apoorva Mandavilli. Antibody Test, Seen as Key to Reopening Country, Does Not Yet Deliver. The New York Times. Available online at https://www.nytimes.com/2020/04/19/us/coronavirus-antibody-tests.html. Published April 19, 2020. Updated May 7, 2020. Accessed June 4, 2020.
Interim Guidelines for COVID-19 Antibody Testing. U.S. Centers for Disease Control and Prevention. Available online at https://www.cdc.gov/coronavirus/2019-ncov/lab/resources/antibody-tests-guidelines.html. Page last reviewed May 23, 2020. Accessed June 3, 2020.
Anand Shah and Jeff Shuren. Insight into FDA’s Revised Policy on Antibody Tests: Prioritizing Access and Accuracy. Food and Drug Administration. Available online at https://www.fda.gov/news-events/fda-voices/insight-fdas-revised-policy-antibody-tests-prioritizing-access-and-accuracy. Published May 4, 2020. Accessed June 3, 2020.
Transcript. Clinical Laboratory COVID-19 Response Call, June 1, 2020. U.S. Centers for Disease Control. Available online at https://www.cdc.gov/safelabs/docs/covid-19-response-calls/06_01_2020_transcript.pdf. Accessed June 8, 2020.
Policy for Coronavirus Disease-2019 Tests During the Public Health Emergency (Revised). Food and Drug Administration. Available online at https://www.fda.gov/media/135659/download. Issued May 11, 2020. Accessed June 8, 2020.