The most pressing issue with these antibody tests is accuracy.
Explore This IssueACEP Now: Vol 39 – No 06 – June 2020
The ELISA tests require significant time and reagent cost but offer the advantage of quantitative antibody titers. These tests are valuable for accurately identifying high levels of circulating antibody for those being considered as possible donors for convalescent plasma donation (although the efficacy of this strategy remains unknown). The prolonged turnaround time and biohazard safety requirements for ELISA reduce its practicality for widespread testing.
In far greater use are LFIA-based devices, which are the widely seen cartridge-based tests. These tests do not typically report a quantitative measurement but provide positive and control color-change lines using a technique similar to home pregnancy tests. The major advantages of these tests are speed and cost. However, they lack the quantitative precision of ELISA.
The most salient issue with these antibody tests is accuracy. The sensitivity limitations of antibody tests are readily apparent because even acute-phase IgM responses are not immediate, usually taking a few days to develop. Therefore, a single antibody test should not be the sole mechanism for diagnosing acute infections. Consideration ought to be given to the time of symptom onset to determine the likelihood of a false negative, as well as either a DNA-based test or a plan to repeat the antibody test in a few days, if negative.
The other accuracy issues stem from antigen synthesis. The challenge for antigen synthesis involves creating a match for a piece of the virus that is both unique to SARS-CoV-2 while also stable enough not to result in mismatches as the virus naturally mutates. The most stable components of SARS-CoV-2 are also the ones conserved across multiple other coronaviruses, resulting in cross-reactivity and false positives. Several common-cold coronaviruses (eg, HKU1, NL63, OC43, 229E, etc.) are known to react with the antibodies in several developed serological tests. A false-positive test may endanger an individual by suggesting potential immunity from SARS-CoV-2 where none exists.
Antibody tests are also being deployed to evaluate the spread of COVID-19 in some communities. This renders false positives especially important. In communities in which little infection is thought to have occurred, the number of false positives can exceed the number of true positives, even in a test with high specificity. These false positives lead to overestimation of the number of potentially immune persons and may misinform public policy decisions.
Each of the several SARS-CoV-2 tests can play a role in detecting individual cases and evaluating the spread of COVID-19. Results must be carefully interpreted in the context of how common (and therefore likely) the disease is. Otherwise, both false-negative and false-positive results from these tests may ultimately place patients, their families, and health care professionals at elevated risk.
The opinions expressed herein are solely those of Dr. Radecki and do not necessarily reflect those of his employer or academic affiliates