New Testing Process Could Make It Faster, Easier, And Less Expensive to Measure COVID-19 Antibody Levels

Researchers testing alternative ways to measure COVID-19 antibody levels have developed a process that is faster, easier and less expensive to use on a large scale, and holds promise for accurately identifying potential donors who have the best chance of helping infected patients through convalescent plasma therapy.

A team of US Army researchers collaborated with scientists at Houston Methodist (Houston, TX, USA), Pennsylvania State University (University Park, PA, USA) and the University of Texas (Austin, TX, USA) to find alternatives to measuring virus neutralization, or VN, titers. These titers are the gold standard of COVID-19 antibody testing, as VN antibodies in the blood have been shown to correlate with levels of protective immunity. According to the researchers, this kind of antibody testing is not widely available as it is technically complex and requires days to set up, run and interpret. Thus, the team looked to another type of test, called enzyme-linked immunosorbent assays, or ELISAs.

ELISAs are standard quantitative tests used to measure the amount of antibody to a particular antigen in a given sample and can also be used for serological monitoring of the disease. Specifically, scientists looked at the relationship of anti-spike ectodomain, or ECD, and anti-receptor binding domain, or RBD, antibody titers in the bloodstream. The spike ECD and RBD proteins are components of the much-talked-about spike protein made by SARS-CoV-2 and are critical to how the virus enters the body, spreads and causes COVID-19 disease. The scientists found that the relative amount of antibody in the bloodstream of COVID-19 patients is linked to their ability to control viral infection; essentially, the more severe the disease, the higher the levels of neutralizing antibody present. This information provides potential benchmarks for a clinical product for convalescent plasma treatment studies; it could also be used to assess how well a vaccine recipient may respond to a subsequent infection.

The researchers found that the ELISA tests had an 80% or greater probability of predicting VN titers at or above the Food and Drug Administration-recommended levels for COVID-19 convalescent plasma. In addition, the researchers found that convalescent donors maintain high levels of immunity over the course of many weeks, and that frequent plasma donations did not cause a significant decrease in antibody or virus neutralization levels. Perhaps most surprising, the researchers said, is that they identified 27 individuals from the surveillance cohort with high enough antibody titers to indicate that some asymptomatic individuals may have plasma suitable for therapeutic use and may have a degree of relative immunity against SARS-CoV-2.

"In all, we discovered that high titer ELISAs correlate well to virus neutralization and can be used as a surrogate for screening convalescent plasma," said Dr. Jimmy Gollihar, biochemist and biotechnologist for the US Army Combat Capabilities Development Command's Army Research Laboratory at CCDC ARL.

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Houston Methodist
Pennsylvania State University
University of Texas