Key Role of Specificity in COVID-19 Antibody Test Accuracy

June 11, 2020

To aid in the medical response to the COVID-19 pandemic, Roche developed a highly accurate antibody test, the Elecsys® Anti-SARS-CoV-2 serology test, which received Emergency Use Authorization from the U.S. Food and Drug Administration (FDA) on May 3. Unlike tests that are used to determine if someone is currently infected with SARS-CoV-2, antibody tests are used to tell if someone has ever been exposed to the novel coronavirus.

Accuracy in antibody testing is essential. An accurate antibody test will::

  1. Correctly identify someone who has been exposed to SARS-CoV-2 and truly has developed antibodies to it – this is known as test sensitivity, or a true positive rate.
  2. Rule out someone who has not been exposed to the virus and has not developed antibodies – this is known as specificity, or a true negative rate.

 

There has been a lot of discussion lately around the accuracy and utility of COVID-19 testing. In making a COVID-19 diagnosis, a healthcare professional must have access to a test with high sensitivity to reduce the likelihood of a false negative, which indicates someone has not been infected with the virus when they have. Many factors can lead to false negatives with diagnostic tests, including PCR tests, which we detail here.

When considering the accuracy of antibody tests, having a high specificity matters more than sensitivity because the greatest clinical risk lies in false positive results. This would mean that someone believes they have been exposed to the virus and has developed antibodies, when in fact they have not. A test with high specificity is more likely to limit the rate of false positives, particularly in populations that have a low infection rate as described below.

Another important factor involved in specificity is cross-reactivity. Instead of detecting antibodies to SARS-CoV-2, an antibody test with low specificity may detect antibodies to other viruses such as those that cause the common cold or influenza – also resulting in a false positive. 

For these critically important reasons, we designed our Elecsys Anti-SARS-CoV-2 assay to maximize specificity. We tested 5,272 blood samples and found our test was 99.81% accurate at ruling out the presence of SARS-CoV-2 antibodies and 100% percent accurate at detecting SARS-CoV-2 antibodies in the blood. Additionally, our test ruled out cross-reactivity to antibodies against related viruses in the 80 potentially cross-reactive samples tested.

Today, with the percentage of people in the population who have antibodies to SARS-CoV-2 being unknown, choosing a test with the highest specificity can facilitate clinical decision-making based on an accurate diagnosis, helping prevent further spread of the virus and saving lives.