COVID-19 Antibody Tests: What We Know and What We Don’t

By Wayne Marasco, MD, PhD, Professor in the Dana-Farber Department of Cancer Immunology and Virology and Professor of Medicine at Harvard Medical School

There is great hope surrounding the release of COVID-19 antibody tests, which could determine whether a person has developed immunity to the virus. We would all benefit if the test results could somehow aid in getting our lives back to some semblance of pre-pandemic days, including getting more of our healthcare providers and staff back to work.

If all goes well (and it is still unknown if it will go well), the antibody tests can have some immediate value to individuals and the world. The tests could certainly empower individuals and their health care providers to make informed decisions about their risk of infection and of spreading the virus.

Still, there are many unknown factors at this point.

What are antibodies?

Antibody proteins are used by the immune system to attack and destroy foreign substances. The job of an antibody is to identify foreign invaders (viruses, diseases, etc.) by binding to specific proteins called antigens on the surface of cells. After they bind, antibodies recruit other cells and substances of the immune system to attack the foreign cells.

These antibodies are very specific for each pathogen, so their detection in your blood or mucosal secretions is an indication of recent and/or past exposure.

Wayne Marasco, MD, PhD.

So what do we know about antibody testing?

As of May 4, 2020, 12 Emergency Use Authorization (EUAs) for antibody tests have been issued by the U.S. Food and Drug Administration (FDA). These tests vary in design and in the type of antibodies in blood that they detect. Some assays test for antibodies to surface spike (S) protein, while other tests detect the structural nucleocapsid (NC) protein. They are all qualitative tests that detect the presence of antibodies in blood, which would indicate prior exposure to COVID-19, but they differ in the type of antibodies that are detected.

In my opinion, the tests that detect immunoglobulin M (IgM) and/or immunoglobulin G (IgG) are the most informative. The detection of only IgM  would indicate a more recent exposure (probably within two weeks); the detection of only IgG would indicate a more distant exposure. The detection of both IgM and IgG would mean a more subacute (recent onset or somewhat rapid). These are relative and not absolute inferences, however. 

What do we still have to learn?

It is still unclear whether the presence of antibodies confers immunity to the COVID-19 virus, to what degree, or for how long. Studies also have yet to establish that test positivity would provide full protection from reinfection.

We still don’t know if the antibody tests have equal specificity and sensitivity, and if their rates of false positive or false negative results are low. The Centers for Disease Control and Prevention (CDC) is currently reporting that the antibody tests are still too inaccurate to be reliably used in decision-making policies; for example, to allow large groups to gather for our educational institutes and state facilities. Additional experience with these tests will be required before any firm conclusions can be made about their general use.

What is the general hope for these tests?

Public health specialists are hopeful that the antibody tests will also provide a better understanding of the true depth of the pandemic, given that a number of children and younger individuals are testing antibody-positive without ever having symptoms of COVID-19 infection.

This has important implications for “herd immunity” — or that level of infection in the population where we could expect a decrease in the spread of infection to vulnerable non-immune individuals. Herd immunity would lead to a decrease in the virus’s mortality rate. Antibody surveillance studies, which are already underway in different national and international studies, should give us a better handle on this aspect of the pandemic.

How could antibody testing affect cancer care?

At Dana-Farber Cancer Institute, we treat a unique subset of patients – cancer patients. There is not enough information on how their cancer diagnosis affects their sensitivity or resistance to COVID-19. An antibody test could provide some additional insight on how to manage their care, particularly if they and their caregivers are planning to institute cancer therapy, whether chemo, radiation or immunotherapy.

There is also the possibility, as some have advocated, that we strategically deploy healthcare workers with COVID-19 immunity to care for our cancer patients. Of course, this circles back to the issue of the qualitative nature of the test: It measures COVID-19 exposure, not immunity.

While we can probably expect some lingering post-pandemic guidelines like social distancing to remain for a while (at least), we all hope that antibody tests will help us to return to some level of “normal.” Clearly, much needs to be learned before we treat them like winning tickets.

In addition to his roles at Dana-Farber and Harvard Medical School, Wayne Marasco, MD, PhD, is an infectious disease physician and has been a scientist in emerging infectious diseases for many years. He has worked extensively in the field of human coronaviruses and was actively working in the field during the 2002-2004 SARS-CoV epidemic in China and the MERS-CoV epidemic that started on the Arabian peninsula.