*Editorial Note: Pfizer's vaccine received full FDA approval on Aug. 23, 2021 for those age 16+. Pfizer is under EUA for ages 12-15. Vaccines from Moderna and J&J remain under EUA as of Aug. 23, 2021.
There is a lot of conjecture about the value of antibody (serologic) testing for COVID-19, what this type of testing will and won’t offer to help us understand the course of the pandemic. To provide clear, up-to-date information and perspective, David Aronoff, MD, Addison B. Scoville Chair in Medicine and Director of the Division of Infectious Diseases, has provided these answers.
What is antibody (serologic) testing?
After suffering from an infection, it is common to develop an antibody response against a particular pathogen.
Early after infection (usually after the first week), a class of antibodies known as immunoglobulin M (IgM) develops, although these are not typically long-lasting. Later, after the first 2-4 weeks following infection, IgG, a more durable antibody, is produced.
Detection of microbe-specific IgM and IgG in circulating blood (a ‘serologic’ test) serves as a traditional method to determine whether a person has been infected with that pathogen, either recently (IgM) or more distantly (IgG).
What could a positive COVID-19 serology test tell us about a patient?
Current data suggest that IgM antibodies against SARS-CoV-2 develop in the circulation after the first week of COVID-19, while IgG antibodies become detectable sometime beyond 14 days of infection.
As a result, detection of specific antibodies (IgM, IgG, or both) against SARS-CoV-2 would suggest that a person has been infected with the virus at some time in the past.
What does a positive serology test not tell us about COVID-19?
Unfortunately, it is not yet clear whether the presence of antibodies against SARS-CoV-2 implies that a person is protected from reinfection by this virus – that is, immunity.
Given the emerging and dynamic nature of the pandemic, more clinical data is needed to determine if a recovered patient is susceptible to reinfection and how mild or severe such an infection might be.
What testing is being developed for the detection of SARS-CoV-2 (COVID-19) antibodies?
Various laboratory methods are being developed to detect SARS-CoV-2 (COVID-19) antibodies, although the rapid emergence of the virus prevents these tests from being subjected to the same degree of validation that diagnostic tests are typically subjected to in the United States before entering clinical care.
A small (but growing) number of tests have received Emergency Use Authorization by the FDA* for clinical care, while many others commercial products remain for research purposes only but are being introduced to the commercial market without passing stringent clinical and analytical validation.
At present, all serologic testing for patient care in the US is required to be performed in accredited clinical laboratory environments.
What are potential limitations of serologic testing?
In addition to the key clinical question of whether SARS-CoV-2 (COVID-19) antibodies imply immunity, additional uncertainties surround their laboratory detection.
These questions are particularly relevant for so-called rapid serologic tests that rely upon lateral flow techniques (i.e. the qualitative appearance of visual bands within a pre-formulated device, similar to a home pregnancy test). In fact, the World Health Organization currently recommends that such tests only be utilized for research purposes, not clinical decision-making.
False-positive results can occur. It is theoretically possible for a serologic test to yield a “positive” result even if a person has never been infected with the targeted pathogen. Occasionally, a person may possess antibodies directed against one microbe, but that cross-react in the laboratory during serologic tests for different pathogens (for instance, related microbes). In the case of SARS-CoV-2, additional research is needed to determine what percentage of non-infected individuals might possess cross-reactive antibodies that could lead to these false-positive results.
False-negative tests can occur. Conversely, even in a patient with a true history of infection, it is possible for their blood not to generate a strong enough signal for a positive serology result. For instance, these false-negative results can occur if a patient cannot generate a robust antibody response due to a suppressed immune system. Even in healthy individuals, the strength and duration of the antibody-response can vary for different pathogens and between individuals.
Research is still ongoing to define these variables for COVID-19 and how they affect the performance and utility of serologic tests.
Is COVID-19 antibody testing available at VUMC?
At this very moment, no, although several methodologies are currently under intense evaluation.
We anticipate offering serologic testing for select patient populations in the near future, although all of the relevant details have not yet been determined (due to the dynamic nature of the situation).
Institutional guidance will likewise be provided on what clinical conclusions/actions should (and should not) be taken based on serologic results. This guidance will be updated as more evidence emerges on the above questions, including the relationship between seropositivity and immunity.