Serology Tests Not Detecting Preventative COVID-19 Antibodies: Is the Public Endangered & Providers Wasting Money?

Serology Tests Not Detecting Preventative COVID-19 Antibodies Is the Public Endangered & Providers Wasting Money

Individual and public health during the COVID-19 pandemic necessitates the evaluation of potential immunity.  Consequently, the generation of antibody response to SARS-CoV-2 (seroconversion) could possibly inform on acquired immunity from past exposure. The antibodies to the SARS-CoV-2 spike protein receptor binding domain (S-RBD) are speculated to neutralize virus infection. However, some serology assays depend on assessment of SARS-CoV-2 nucleocapsid protein (N-protein) as antibody detection antigen. The problem: it is unknown if the N-protein immune response correlates with the important S-RBD response and, hence, true immunity remains unknown. Recent study results published in the JCI Insight suggests that “extensive use” of commercial serology tests from diagnostic manufactures that may serve to confirm the presence of N-protein antibodies could potentially risk misleading the public to believing, incorrectly, that they are protected from a SARS-CoV-2 reinfection. MD Anderson Cancer Center researchers caution that commercial serological tests mostly validate the presence of N-protein antibodies but the S-RBD antibodies are the best known indicator of possible protection from reinfection. Consequently, a delta exists between what should be tested and evaluated and what is actually tested and evaluated. Is this leading the public to danger? Are providers throwing away money on products that don’t generate the proper answer?

TrialSite breaks down this situation.

Why did MD Anderson embark on this study?

To better understand if commercial tests on the market are safe or whether they may lead to more risk

What antibody has MD Anderson discovered may neutralize the SARS-CoV-2?

Antibodies to the SARS-CoV-2 spike protein receptor binding domain (S-RBD) are speculated to neutralize virus infection.

But what about SARS-CoV-2 nucleocapsid protein (N-protein) antibody?

Well, as it turns out, this antibody may often only indicate exposure to the virus, but not represent protection against reinfection.

Why is this a problem?

The available commercial tests are validating the presence of these N-protein antibodies, which means that there is growing speculation, thanks to the MD Anderson study, that providers buying these diagnostic technologies are spending money on something that may not offer the results that they expected. Moreover, consumers/patients may be lulled into a false sense of security thinking that they are now somehow immune when in fact they may not be.

The Study

The team conducted a study using serological enzyme-linked immunosorbent assay (ELISA) using SARS-CoV-S-RBD and N-protein for the detection of circulating antibodies in 138 serial serum samples from COVID-19 serum samples collected between June 2017 and June 2020.

What were the results?

3% of healthy and non-COVID-19 samples collected during the pandemic in Houston were positive for the N-protein antibody, but only 1.6% of those had the S-RBD antibody.  

Of samples with the S-RBD antibody, 86% had neutralizing capacity (they can prevent COVID-19), but only 74% of samples with N-protein had neutralizing capacity. When positive for both, 96.5% exhibited neutralizing capacity.

What are the implications of this study

Raghu Kalluri, MD, PhD, professor and chair of Cancer Biology and senior author, articulated in a recent MD Anderson press release that the findings point toward a problem with depending on N-protein detection as assurance that neutralizing antibodies are in place, stating, “the presence of S-RBD antibody is the best indicator of any potential protection against reinfection.”

What is the implication for the market?

Dr. Kalluri, representing MD Anderson, cautions, “against the extensive use of N-protein based serology testing for determination of potential COVID-19 immunity.” He recently made it clear that “accurate and reliable S-RBD serological testing is needed to carefully identify individuals with neutralizing antibodies in order to help advance recovery around the globe.”

What does the current market offer?

Currently, a number of commercially available serology tests can only confirm the presence of N-protein, with over 200 commercial and hospital laboratory testing facilities using these tests. Again, the tests may indicate exposure to the virus they do not seem to suggest immunity to reinfection.

What needs to happen?

Providers and the public need to be educated on what antibody tests even mean for each patient, and public health efforts should center on ways to encourage patients to continue vigilant safety precautions, even with the presence of N-protein antibodies.

Lead Research/Investigator

Raghu Kalluri, MD, PhD, professor and chair of Cancer Biology

Kathleen McAndrews, PhD postdoctoral fellow in Cancer Biology

Luis L. Ostrosky-Zeichner, MD

Ramesh Papanna, MD, University of Texas Health Science Center (UT Health)

Call to Action: Check out the study. Providers should make sure their clinics understand the implications of this study.