First Detailed Analysis of Which Antibodies Best Neutralize SARS-CoV-2 in COVID-19 Patients Could Improve Serological Tests

Scientists have performed the first detailed analysis of different antibodies produced by COVID-19 patients to various parts of SARS-CoV-2 and determined which of them had the strongest neutralizing activity against the novel coronavirus.

Scientists at Fujita Health University (Aichi, Japan) undertook the first detailed investigation of how different antibodies (or antibody “isotypes”) interact with the various antigens produced by SARS-CoV-2 in COVID-19 patients.

Blood tests to detect antibodies against SARS-CoV-2 are an important tool for diagnosing the disease, developing potential treatments, and checking vaccine efficacy. Although such tests are available, we have very little understanding on how different antibodies interact with virus antigens. Besides the now widely known PCR test, there is interest in serological (blood) tests that detect “antibodies” against SARS-CoV-2. These blood tests have considerable applications, from identifying blood donors with high levels of anti-SARS-CoV-2 antibodies, whose blood can be used for convalescent plasma therapy, to measuring vaccine effectiveness.

Antibodies are proteins produced by the body’s immune system to combat foreign proteins, such as the SARS-CoV-2 virus. Antibodies function by binding to a specific part of the virus that the immune system recognizes, called “antigens.” SARS-CoV-2 is composed of four major proteins, with two being highly immunogenic (capable of producing an immune response). These immunogenic proteins are called spike (S) and nucleocapsid (N) proteins. Presence of antibodies specific to the S protein means there is a higher amount of virus-neutralizing activity while antibodies specific to N protein indicate the presence of previous SARS-CoV-2 infection.

Despite this general awareness, we actually have only a vague understanding of how different antibodies (or antibody “isotypes”) interact with the various antigens produced by SARS-CoV-2. Hence, a team of scientists undertook the first detailed investigation of these interactions through an analysis of blood samples from 41 COVID-19 patients. The team developed assays using three common antibodies (IgG, IgM, and IgA), each of them split into isotypes that bind specifically to five antigens (three parts of the S protein, including the receptor binding domain [RBD], the full S protein, and the full N protein).

The results of their experiments showed that all antibody isotypes that bind to the S protein (full and parts) were highly specific, but antibody isotypes binding to the N protein were less so. With minor variations, all antibodies are detectable in patients at approximately 2 weeks after symptoms appear, and detection sensitivity was higher than 90% (except in the case of IgM binding to N protein). Importantly, the researchers showed that IgG specific to the RBD of S protein had the highest correlation with virus neutralizing activity and disease severity. In other words, measuring RBD-specific IgG levels could tell us a lot about the immune response of COVID-19 patients, and could be the foundation for improving COVID-19 blood tests.

“We are also very excited by our findings because of their implications for convalescent serum/plasma therapy, a type of treatment where you transfuse blood from people who recovered from COVID and have high levels of antibodies against SARS-CoV-2,” said Senior Assistant Professor Hidetsugu Fujigaki from Fujita Health University who led the team of scientists. “Being able to show that the IgG antibody against RBD is highly correlated with neutralizing activity means we can identify appropriate blood donors for this treatment.”

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Fujita Health University