The Quest for Accuracy: Not all Antibody Tests are Created Equal

August 3, 2020
By: Stephen Rawlings, Ph.D. - Scientist, University of California - San Diego

Dr. Stephen Rawlings is a resident physician in his last year of infectious disease fellowship at University of California, San Diego. His desire to help improve the world led him to the lab of Dr. Davey Smith, where the team seeks to understand viruses that can cause human disease and reverse it, so people have longer, healthier lives.

Pre-COVID-19, Dr. Rawlings was focused on HIV, predominantly trying to answer questions about where in the body HIV reservoirs “hide out.” Reservoirs are the sources of rebound viruses; if someone has HIV, and ever stops taking their medication to fight the virus, it comes back. They know it comes back from different parts of the body, and they are working to understand where in the body it’s coming from, and what’s allowing it to hide there. When COVID-19 surfaced, it made sense for the team to tackle that in the same way to help determine what to use in terms of protecting people in the future.

Dr. Rawlings shares how his team is working to help improve testing options and discusses utility and the importance of taking the necessary time for quality research.

How is your team collaborating with industry?

We are fortunate to have a very robust sample set, having collected a variety of fluids from individuals beginning when San Diego had evacuees from Wuhan, China and were sent to Miramar for quarantine, up to recent COVID-19 patients in the hospital and field from whom I routinely collect samples. Because we have these samples from individuals who became participants in our studies, one goal we set is to help improve test development. Testing for antibodies has proven to be important and we realized early on that the options weren’t always great. It’s hard to discern between different types of coronavirus antibodies. We were seeing a lot of cross reactivity in tests, which can cause false positives. And given that we are seeing how immune responses vary so greatly between people, developing one test that can positively identify everyone with specific antibodies (accurate sensitivity rates) is challenging. Our samples have been very useful in characterizing tests that can discriminate and provide accurate identification of those with the antibodies, without providing false positives, which we found the Easy Check COVID-19 IgM/IgG test can do. Our data also suggests that even some of our hardest cases, that weren’t picked up by other tests, were picked up by Easy Check, our COVID-19 antibody test.

What do you see as the utility of understanding, or identifying those with, SARS-CoV-2 antibodies?

It’s a huge question for the whole community: Does a positive antibody test mean you won’t get the virus should you see it again? Classically, that’s how it works with other viruses; if you get a strain, you won’t get it again in the very near future. There’s the hope to discover that a certain antibody is neutralizing, and therefore you will be protected, but until that research is complete, we simply don’t know for sure. What we do know, is that it’s now been 6 months and there have been no real solid cases of people who have been re-infected, which suggests that nature is doing what it does and protecting us from a repeat infection. We therefore suspect it works like other viruses, but researchers looking to understand the virus need more samples from individuals with the SARS-CoV-2 antibodies to keep studies progressing.

At an individual level, knowing whether or not you have the antibodies might help inform your behaviors or decisions; you might be cautious, or you might be willing to donate your plasma to help those who are critically ill with COVID-19. At a population level, we need to better understand the prevalence of the virus to inform important decision making in hospitals, schools and in communities as a whole.

We do have some collaborators who have already identified some very good antibody candidates for either therapeutic or intelligent vaccine design, as well. There is hope that all the information being collected, combined with all the researchers sharing around the world, will lead to breakthroughs that provide a solution to this.

Can you share a key takeaway from the past 6 months?

If there’s one thing we’ve learned it’s that high quality science is incredibly important. Papers have been published and then retracted. Tests made it to market, and then had to be pulled because they were too unreliable. Treatments have been pulled. While we all want speed, the need for high quality research is still there.

Taking the time to “test tests” with as many samples as we can is critical. This is important and necessary in-the-trenches kind of work that we just can’t shortcut, it simply has to be done really well at the beginning; and, in time, it will bear out excellent results.

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