Roche recently received Emergency Use Authorization by the Food and Drug Administration for its SARS-CoV-2 antibody test. Laura Parnas, PhD, Senior Scientific Affairs Manager for Roche Diagnostics, answers some critical questions about the Elecsys® Anti-SARS-CoV2 assay, Roche’s latest tool to aid in the healthcare response to COVID-19.
Dr. Parnas: The fundamental job of an antibody is to recognize foreign invaders in the body and block them from causing harm. An antibody test, also known as a serology test, is a blood test that can provide information about a person’s immune response to a pathogen.
In the current situation of the COVID-19 pandemic, an antibody test can help detect how many people have or have not been exposed to SARS-CoV-2, the virus that causes COVID-19. Antibody tests can help health professionals better understand the spread of the virus and to aid in identifying potential human plasma donors who may help those infected better fight the virus. Because this is a novel pathogen, we don’t yet know whether having antibodies provides protection against re-infection.
Roche thoroughly evaluated its assay by testing well over 5,000 samples, with the following results:
Dr. Parnas: An antibody test can be designed in three ways:
The Elecsys Anti-SARS-CoV-2 assay is unique among the currently commercially available tests because it is designed specifically to detect high-affinity antibodies to SARS-CoV-2 regardless of the antibody class.
Dr. Parnas: Antibodies evolve as they respond to a pathogen. When a virus first appears in a person, their body will initially generate antibodies that have a low affinity for the virus, meaning they are unable to effectively attach to the virus and eliminate it.
As a person’s immune response evolves, it will produce high-affinity (mature) antibodies that attach to the virus with the potential to neutralize it. These high affinity antibodies appear later in the course of the infection. IgG is an antibody that traditionally appears late in the immune response; however, there is evidence of low affinity IgGs appearing at the onset of SARS-CoV-2.2,3 The ability to distinguish between low and high affinity antibodies can increase the overall accuracy of an antibody test.
Dr. Parnas: Only a very small subset of antibodies generated in an infection are neutralizing antibodies – a type of antibody that binds to a virus and blocks it from infection. Antibody tests by nature are not designed to distinguish between neutralizing and non-neutralizing antibodies; however, tests directed towards the detection of high affinity antibodies increase the likelihood of including neutralizing antibodies. At this time, there is no definitive evidence about the presence of neutralizing antibodies in SARS-CoV-2 exposed patients or whether the presence of an immune response confers protective immunity, but evidence continues to be generated.
Dr. Parnas: Significant research and development drove our decisions around our test design, and we tested over 40 different assay formats to select the best one. The key factor was ensuring our test was highly specific for high affinity antibodies against SARS-CoV-2 only. Tests that are designed to detect a specific antibody class may not distinguish between low and high affinity antibodies, making them less specific. Since our test is designed to only target high affinity antibodies, it minimizes the risk of detecting antibodies from other viruses, such as those that cause the common cold or flu that can result in false positives.
Dr. Parnas: A good test has high levels of sensitivity and specificity. Sensitivity refers to the ability of a test to detect the presence of antibodies to SARS-CoV-2. Specificity means that the test can detect individuals who have not been exposed to SARS-CoV-2. For antibody tests, having high specificity means you are more likely to limit the rate of false positives. High clinical specificity is also critical as some populations have a low SARS-CoV-2 infection prevalence, which ultimately influences the positive predictive value (PPV) of the test. Tests designed with maximum specificity improve the confidence for providers to determine who has been exposed to SARS-CoV-2, especially in low prevalence populations.
Dr. Parnas: Right now, the clinical community is working to evaluate the immune response to this novel virus and whether the antibodies that have been generated so far 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.