How reliable are coronavirus antibody tests? It is likely that they undercount past infections, warns CDC
Most persons infected with SARS-CoV-2, the virus that causes Covid-19, develop virus-specific antibodies within several weeks. Antibody tests check the blood by looking for antibodies, which may tell a person if he or she had a past infection coronavirus. Researchers, however, suggest that antibody testing likely undercounts the number of people infected with Covid-19 in a new analysis. The team from the US Centers for Disease Control and Prevention (CDC) found that 28% of healthcare workers who had previously tested positive for antibodies did not have enough antibodies to test positive 60 days later.
The CDC cautions that because antibody levels decline over time, antibody testing cannot conclusively show a person has not had Covid-19 in the past. They advise that until more is known about immunity following infection, people should wear a mask, stay 6 feet from others, wash their hands often, and avoid gatherings.
“In this study of frontline health care personnel at 13 medical centers who received positive SARS-CoV-2 antibody test results in spring 2020, more than one quarter were seronegative approximately 60 days after testing. Because SARS-CoV-2 antibody levels might decline in a proportion of persons following primary infection, a negative serology test does not reliably exclude previous infection, write authors.
The CDC emphasizes that these antibody declines might not equate to loss of protective immunity or increased risk for reinfection and disease, as this was not assessed in the report.
The findings
According to experts, once infected with Covid-19, antibodies usually become detectable in the blood two to three weeks after someone has coronavirus. A positive result from a serology or antibody test may mean that a person was previously infected with the virus. Seroprevalence is the percentage of individuals in a population who have antibodies to an infectious agent.
Serology tests are now being used widely in seroprevalence studies to understand patterns of viral spread, the cumulative incidence of SARS-CoV-2 infection, and pandemic trajectory. “Further, serologic testing has been proposed as a way to identify persons who might have developed immunity through a previous infection. Understanding how rapidly SARS-CoV-2 antibody levels decline after seroconversion is critical for interpreting serology results. However, the frequency and timing of seroreversion (the decline in antibody levels below the positivity threshold after initial seroconversion) remain largely unknown,” write investigators.
The current analysis involves frontline US healthcare personnel who received positive SARS-CoV-2 antibody test results in spring 2020 and returned for follow-up testing. Serum specimens were collected at 13 hospitals and tested for antibodies to SARS-CoV-2 during April 3-June 19, 2020, and again approximately 60 days later to assess this timeline.
Overall, 194 (6%) of 3,248 participants had detectable antibodies to SARS-CoV-2 at baseline. However, upon repeat testing approximately 60 days later (range of 50-91 days), 146 of 156 (93.6%) healthcare workers who returned for follow-up had a decline in antibody levels between baseline and follow-up. Another 44 (28.2%) had complete seroreversion, that is, a decline of antibody to levels below the threshold for positivity. Participants with higher initial antibody responses were more likely to have antibodies detected at the follow-up test than were those who had a lower initial antibody response.
The results suggest that a substantial proportion of persons infected with SARS-CoV-2 might have negative serologic test results in the months following infection, say experts. They warn that serology testing at a single time point to evaluate population immunity is likely to underestimate the number of persons with previous SARS-CoV-2 infection.
“This has several important implications. Cross-sectional seroprevalence studies that estimate the number of persons who have been infected with SARS-CoV-2 will likely underestimate incidence because a proportion of previously infected persons will likely serorevert and thus not be counted as having been previously infected. In addition, these results challenge the notion of using serologic testing results at an individual level to designate previous SARS-CoV-2 infection,” explain researchers.
Covid-19 convalescent plasma is widely being used as a treatment for the disease, including through a Food and Drug Administration (FDA) Emergency Use Authorization (EUA) in the US. Based on their results, the authors say that the optimal window for collecting convalescent plasma with high levels of SARS-CoV-2 antibodies from donors who have recovered from coronavirus might be short because of a substantial decline in antibody levels within 60 days.