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New technique can be used to test for COVID-19 immunity

In late February, Dr. Stephen Smith of the Seattle Children’s Research Institute suspected that he had been infected by the coronavirus. Since his symptoms did not qualify for COVID-19 testing at that time, Dr. Smith set out to create a method for testing himself. The results of his work are now being translated into a new technique of testing for the presence of neutralizing antibodies that could provide individuals with COVID-19 immunity. 

“If you think you’ve had COVID-19 and go to the doctor, they can test your blood and tell you whether or not you have antibodies to COVID-19, but that doesn’t tell you whether your antibodies are any good at functionally blocking the virus from binding to cells,” said Dr. Smith. “There are tests on the market now that can tell you that, but they are expensive and take a long time to get results. We wanted to develop a way to give you additional information about your immune status without all the barriers that make it difficult to use in a community setting.”

SARS-CoV-2 invades the body by binding its spike protein to specific receptors on the surface of human cells. Antibodies that block this binding are believed to provide immunity in people who have recovered from COVID-19 infection.

Dr. Smith used a technique called immunoprecipitation detected by flow cytometry (IP-FCM) to look for evidence that antibodies could block the virus from binding to cells. While current blood testing relies on live cells and viruses, IP-FCM uses proteins developed in the lab.

“Other tests that provide insight into immunity work by taking antibodies from your blood and mixing them together with a virus and then exposing that mixture to live cells. Three days later they can determine immunity based on whether your blood prevented the viruses from infecting the cells or not,” said Dr. Smith. “Our cell-free test can provide that same information overnight.”

Dr. Lisa Frenkel and Dr. Whitney Harrington from the Center for Global Infectious Global Disease Research are following a community cohort of Seattle Children’s employees who have recovered from mild to moderate COVID-19 without being hospitalized. Dr. Smith is collaborating with the researchers to investigate immune responses to SARS-CoV-2.

Using IP-FCM, Dr. Smith tested blood samples from 24 cohort participants. The analysis revealed that 92 percent of the participants had developed COVID-19 antibodies about a month after they were infected. 

“Not only did the participants have antibodies, but our test also showed that their antibodies were pretty effective at neutralizing the binding between the spike protein and the cell’s receptor,” said Dr. Smith. “It’s consistent with other studies from cell-based tests showing that people who get COVID do make neutralizing antibodies.”

The researchers also discovered that individuals who developed a fever during COVID-19 infection had higher levels of antibodies. 

“It’s going to be very important to look at people over a longer time period to track their antibody levels and whether or not they get re-infected,” said Dr. Smith. “Until we do those studies, we really don’t know how these clinical measures of antibody neutralization relate to susceptibility in the real world.”

The team is now using Dr. Smith’s testing technique to screen thousands of approved drugs that could potentially block the spike protein from binding with human cells.

The study is published in the Journal of Infectious Diseases.

By Chrissy Sexton, Staff Writer

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