Study brings us one step closer to a universal antibody test for COVID-19

A new study published by Houston Methodist brings researchers a significant step toward developing a uniform and universal COVID-19 antibody test. The multicenter collaboration tested alternative ways to measure COVID-19 antibody levels that are faster and easier and can be used inexpensively on a larger scale to accurately identify potential donors with the best chance of helping those SARS-CoV-2 virus infected patients with convalescent patients. plasma therapy.

The findings will also have applications beyond determining who the best plasma donors are. The consensus among the study authors is that after donor identification, it will most likely be used in practice to establish target levels of COVID-19 antibodies that individuals should be considered candidates for passive immune therapies and vaccines. .

Additional uses to come later and likely to have the greatest social impact, the researchers say, are to assess relative immunity in those previously infected with the SARS-CoV-2 virus and to identify asymptomatic individuals with high levels of neutralizing antibodies against SARS. -CoV- 2.

Donors who experienced shortness of breath (or dyspnea) while infected with COVID-19 and those who were hospitalized or had a severe illness were also found to be more likely to have a robust immune response and therefore had higher levels. high neutralizing antibodies in all tests. In the absence of available evidence, identification of donor characteristics can be used as a contingency plan to determine which patients have developed higher levels of antibodies and inform efforts to recruit plasma donors for therapeutic purposes.

In collaboration with Penn State, the University of Texas at Austin, and the U.S. Army Infectious Diseases Medical Research Institute, study authors James M. Musser, MD, Ph.D. and Eric Salazar, MD, Ph.D., medical scientists at Houston Methodist, sought to find alternatives for measuring virus neutralization (VN) titers, which is the gold standard of COVID-19 antibody testing, since VN antibodies in the blood correlate with immunity. This type of antibody test, however, is not widely available, because it is technically complex, requires days to set up, run, and interpret, and must be performed in a biosafety level 3 laboratory. This leads to the majority of donor plasma virus antibody levels remaining unknown prior to transfusions, thus requiring an easier and more available method to identify more suitable convalescent plasma donors.

Therefore, the research team sought out another type of test, called ELISA assays, that can be relatively easily implemented and performed in a high-throughput form and are widely available and widely used in clinical laboratories around the world. ELISA tests, or enzyme-linked immunosorbent assays, examine for antibodies to SARS-CoV-2 proteins and produce a quantitative measure of those antibodies. The UT Austin research team developed the ELISA antibody test for SARS-CoV-2 and provided the viral antigens for this study.

Specifically, the scientists analyzed the ratio of anti-ectodomain IgG bloodstream antibody titers (ECD) and anti-receptor binding domain (RBD). The ECD and RBD spike proteins are physiological parts of the much-talked about spike protein produced by SARS-CoV-2 and critical to how the virus reaches the body, spreads, and causes COVID-19 disease, thus which are prime targets for antibody testing and vaccine development. Blood samples for the study were identified during an institutional surveillance program that involved 2,814 Houston Methodist employees.

The aim of the study was to test the hypothesis that anti-ECD and anti-RBD IgG bloodstream antibody titers correlate with VN titer, making these ELISA tests more accessible and easy to perform as a surrogate marker to identify plasma donors with titers above the threshold recommended by the US Food and Drug Administration for donating convalescent plasma.

When evaluating the correlation between VN antibody levels and anti-RBD and anti-ECD ELISA protein titers data, the researchers found that ELISA tests had an 80% or more probability of an antibody level comparable to titers. of NV at or above the levels recommended by the FDA. for COVID-19 convalescent plasma. These results affirm that all three types of tests could potentially serve as a quantitative target for therapeutic and prophylactic treatments.

They also found that convalescent donors maintain high levels of immunity over the course of many weeks and that frequent plasma donations do not cause a significant decrease in neutralizing levels of antibodies or viruses.

Perhaps most surprisingly, they also identified 27 individuals from the surveillance cohort with high enough antibody titers on all three tests to indicate that some asymptomatic individuals may have adequate plasma for therapeutic use and may have a degree of relative immunity against it. SARS-CoV-2. .

Ultimately, the study successfully concluded that anti-RBD or anti-ECD IgG antibody titers can serve as surrogates for VN titers to identify suitable plasma donors and that these alternative ELISAs can provide critical information on immunity. COVID-19.