Question: I know you’ve already talked about antibodies and antibody tests before, but the recent NYTimes article, “Why Antibody Tests Won’t Help You Much,” made me want to know what an effective antibody test would look like. What should they be testing for if they want to know if you’ve actually had it (assuming that having had it confer immunity for at least a couple of years)?
Answer: Yes, we have talked a good deal about antibody testing over the months (see Q&As of 4/13 #Antibody, 4/15 #Specificity, 5/21 #Monitoring, and 8/7 #Immunity), but there’s always more to write because we’re always learning more! To summarize the Times article for those who haven’t read it — the Infectious Disease Society of America released guidelines on antibody (serologic) testing earlier this month, which concluded with 8 recommendations, including:
- Don’t use antibody tests to make individual-level decisions about risk. “Based on the available evidence at this time, serologic tests should not be used to determine immunity or risk of re-infection. Thus, anti-SARS-CoV-2 antibody detection cannot inform decisions to discontinue physical distancing or lessen the use of personal protective equipment.”
- Do use antibody tests for population-based epidemiologic studies and in 2 clinical scenarios. “In addition to use in epidemiologic studies, the panel identified two clinical scenarios where antibody testing was felt to have potential utility for diagnosis…[1] Serologic testing may be helpful in the evaluation of individual patients with a high clinical suspicion for COVID-19 when the results of molecular diagnostic testing are repeatedly negative or such testing was not performed…[2] Detection of anti-SARS-CoV-2 antibodies is also useful for assessments of suspected multisystem inflammatory syndrome in children.” Now to get back to your question…
What should they be testing for if they want to know if you’ve actually had it (assuming that having had it confer immunity for at least a couple of years)?
Here the challenge is that we still don’t know how long after infection immunity lasts, how robust our immune response would be in response to potential reinfection, and whether immune response would differ by a/symptomatic status. The assumption underlying your question — which is the major assumption underlying the purpose of individual-level antibody testing — is still just an assumption. In fact, we have accumulating evidence that antibodies decline quite rapidly after COVID-19 infection, especially among asymptomatic individuals. For example, this small study out of China published in Naturefound that 40% of asymptomatic patients became seronegative within 8 weeks of hospital discharge. This article from GAVI gives a nice overview of the issues. So even if we had the perfect antibody test, it still might not be telling us individually anything of significance. Here, we need more information on lasting immunity, reinfection, and the like. Since antibodies are only one component of our complex immune systems, we also need more information on whether immunity lasts regardless of presence/absence of antibodies. Here is another promising avenue for research — the study of T-cells.
Testing for T-cells
Since T-cell immunity may last longer than B-cell immunity (B-cell antibodies are detected in current antibody tests), a bigger push of late has been to study T-cell immunity (as discussed in Q&A of 8/6 #T-cells). For example, a study out of Sweden published in Cell a couple of weeks ago found among other interesting results, that “memory T cell responses were elicited in the absence or presence of circulating antibodies.” This seems very promising. However(!), we still don’t know what degree of immunity lasting T-cell response confers. And as described in the aforementioned GAVI article, “as T cells only respond to the virus once it has already invaded host cells, there is a possibility that people may still be able to transmit the virus even if they do not themselves develop disease.” Finally, T-cells are harder to measure than antibodies, but there are tests that do allow for it.