In the largest study to date looking at the antibodies produced by people who have recovered from COVID-19, researchers uncovered a few surprises that could have implications for not only how useful antibody-based treatments might be, but also what the results from an individual’s antibody test actually means.
Right now, most people that get antibody tests want to learn if they have been infected with COVID-19 or not, since so many experience mild, or no symptoms of the illness. But that information could in theory be used to answer questions well beyond personal curiosity. For public health experts, these results are important for getting an idea of how deeply COVID-19 penetrated specific communities, and how widespread the infection was—and, how rampant it could potentially become again. The more people who get tested, the more accurate such prevalence data can be. But there are other, equally critical ways that antibody testing could help to monitor and ultimately control the pandemic in coming months.
In the study published in medRxiv, a preprint server for posting studies before they are peer-reviewed, a team at the Lindsley F. Kimball Research Institute of the New York Blood Center and Rockefeller University analyzed 370 plasma samples donated from people who recovered from COVID-19 and found some surprising results. The researchers used several antibody testing methods, including two commercially available tests, to document levels of immune system antibodies those patients generated against SARS-CoV-2, the virus behind COVID-19. (All produced similarly reliable readings.) The researchers then tested these antibodies against a SARS-CoV-2 virus substitute in the lab to see if the antibodies could actually neutralize the virus (such stand-ins, which mimic actual viruses without being infectious, are often used to laboratory research settings to avoid spreading disease).
Overall, around 88% of the people generated varying levels of antibodies to the virus. But only about 10% of them had high levels that were able to neutralize the lab-based version of the COVID-19 virus—and, on the other side of the spectrum, 17% had almost no antibody response to their infection.
What that means is so-called “natural immunity” to SARS-CoV-2 may be more complicated than the idea that everyone infected with COVID-19 is robustly protected from getting the disease again, says Dr. Larry Luchsinger, assistant member at the research institute and the lead author of the paper. “There was a very significant group of people who had essentially no neutralizing activity [against the virus]. What we found was that surprisingly, across all tests, there was a very wide deviation or range of antibody results that people were experiencing.”
More data needs to be collected to understand why recovered patients have such a wide range in antibody levels, and how that could affect people’s ability to fight off future infections with the virus. The findings imply, for example, that there may be different ways of fighting SARS-CoV-2 infection. Since all of the people recovered from their infections, some people’s immune systems may rely heavily on antibodies, while others turn to different types of cells to fend off the virus.
The results make a strong case for doctors to not just test for antibody levels, but to learn what those levels might mean for each patient’s ability to fight further infection. Making those sorts of determinations isn’t possible yet, but it might be with more data on the antibody levels of recovered patients.
“At this very moment, little is known about antibodies and their utility,” Michael Mina, assistant professor of epidemiology and faculty member at the Center for Communicable Disease Dynamics at the Harvard T.H. Chan School of Public Health said in a question-and-answer session with reporters. As more data become available, doctors might be able to determine what level of antibodies are more likely to provide protection against getting infected with SARS-CoV-2 again, and share this information with their patients, who would then know how vulnerable they might be to re-infection.
Luchsinger’s results are a start for building that data; the study does include detailed results on levels of two commercial antibody tests, one from Ortho and the other from Abbott, as well as results on how well those antibodies identified by the tests could neutralize the virus in a lab setting. However, “The unfortunate thing is, the only way to know [for sure] what level of neutralizing activity is required is to take individuals and re-expose them to COVID-19,” Luchsinger says. “There are ethical dilemmas in doing something like that.”
Still, being able to use antibody tests to identify people who have little ability to neutralize the virus, and those who are better able to do so, could be important in advising them about how they can stop the spread of COVID-19. “The people who don’t have a lot of neutralizing activity should be cautious, and take precautions to keep themselves and their loved ones safe,” says Luchsinger.
To get a fuller picture of what antibody responses to COVID-19 actually mean for immunity, Luchsinger is expanding the study and matching up people’s antibody levels with their symptoms, to see if there is any correlation between how severe people’s symptoms were and how actively their antibodies could neutralize the virus.
Such information will be even more crucial in coming months, as employers and public health officials rely on these data to track how people can stay safe in communities when they are at work, or using public transportation or at public gatherings. Antibody testing will also be important as vaccines are rolled out, as public health officials will likely want to get vaccination to those with low or no antibody levels, who are more vulnerable to infection. Tracking these antibody levels over time among the vaccinated will also give experts useful information on how well the vaccines are working.
“We just have to be a little patient and let the studies come in,” says Mina. “But the infrastructure for antibody testing needs to be built up even if right now we’re not seeing immediate benefit beyond [finding people who have been infected].”