What Makes an Antibody Test Accurate?

June 8, 2020

With the COVID-19 pandemic continuing to impact society on a global scale, antibody tests have been introduced to aid in the public health response. Antibody tests (also called serology tests) detect the presence of antibodies to SARS-CoV-2 in the blood. Different from a diagnostic test, an antibody test is intended to show if a person has been previously infected with the virus and developed an immune response. 

Our Elecsys® Anti-SARS-CoV-2 antibody test received Emergency Use Authorization from the U.S. Food and Drug Administration (FDA) on May 2. The test is uniquely designed to reliably identify high-affinity antibodies developed late in the immune response to SARS-CoV-2.

 

Why High- and Low-Affinity Antibodies Matter More than Antibody Class

When a person is infected with a virus for the first time, an immune response is triggered to fight the infection with the production of antibodies. While these early antibodies play an important role in kick starting the immune response, they have a low affinity for the virus itself, preventing them from binding to the virus and eliminating it. As the immune response to the virus evolves, the immune system produces high-affinity antibodies, which are the antibodies that attach to the virus with the potential to neutralize it. Because high-affinity antibodies develop over a longer period, people who are tested too soon after developing symptoms may not have produced these antibodies yet.

Antibodies fall into different classes which typically follow a predictable path. Upon exposure to an infectious agent, immunoglobulin M (IgM) antibodies appear first and immunoglobulin G (IgG) antibodies appear later. Most of the COVID-19 antibody tests currently in use detect only the antibody class – primarily, IgG antibodies. However, we are learning that in COVID-19, the production of these two antibodies may significantly overlap or even appear when they are not normally expected. This means a person could have both low-affinity IgG antibodies and low-affinity IgM antibodies in their blood, which could skew an antibody test result.

The Elecsys Anti-SARS-CoV-2 test is specifically designed to detect only high-affinity antibodies, regardless of the antibody class. This ability to selectively target high affinity antibodies increases the overall accuracy of the antibody test.

 

Knowing the Best Time to Get an Antibody Test

For molecular-based testing, where the purpose is to determine if a person has been infected with SARS-CoV-2, it is crucial testing happens as soon as possible after the onset of symptoms. The purpose of an antibody test, however, is to determine if a person was previously infected with the virus and developed antibodies for it. The optimal time for antibody testing is after the body has had time to develop an immune response. Data so far shows that high affinity antibodies are reliably detectable as soon as two weeks after confirmation of SARS-CoV-2.

While asymptomatic patients may not know when they were exposed to the virus, antibodies can remain in the body for some time. With other coronaviruses like SARS and MERS, high-affinity antibodies typically peak within months of an infection and can last for a year or more.

 

The Connection Between High-Affinity Antibodies and Immunity

As SARS-CoV-2 was identified just a few months ago, the science continues to evolve regarding the immune system’s response to this novel pathogen. During a typical immune response, the body generates a small subset of antibodies called neutralizing antibodies, which bind to a virus particle and prevent it from infecting a cell. Although antibody tests do not distinguish between neutralizing antibodies and non-neutralizing antibodies, tests directed at the detection of high-affinity antibodies increase the likelihood of also detecting neutralizing antibodies.

We don’t yet know whether the presence of antibodies to SARS-CoV means someone is protected against re-infection, how long this potential immunity might last, or whether the antibodies that are generated are in fact neutralizing antibodies. As the disease and our knowledge of it evolves over the coming weeks and months, we hope to better understand the role of antibody tests in identifying immunity in individual people. A highly accurate test – with high specificity – may help answer those critical questions.