FDA increased oversight of antibody testing on May 5, requiring them to meet standards of other molecular tests.
FDA has granted Truvian Sciences Emergency Use Authorization (EUA) for its Easy Check COVID-19 IgM/IgG antibody test. The company said it plans to produce the test “at mass scale” in the United States and make it immediate availability to US health care providers.
Company officials said in a statement released today that the test exceeds EUA requirements, including a sensitivity rate of 98.44% a specificity of 98.9%. The cross-reactivity evaluation determined no cross-reactivity (0%) with HIV, influenza A and B, and several coronavirus strains.
Also, the test was validated by the Frederick National Laboratory for Cancer Research, under a partnership among the FDA, the CDC, and the National Cancer Institute. The reported combined sensitivity of 100% and combined specificity of 97.5%.
FDA increased oversight of antibody tests on May 5, requiring them to meet standards of other molecular tests. Later that month, 28 tests were pulled off the market. The interagency confirmation project launched around that time and called for government scientists to ensure that tests were picking up only antibodies for the novel coronavirus (SARS-CoV-2) and not other antibodies.
The American Journal of Managed Care® (AJMC®) interviewed Jeff Hawkins, president and CEO of Truvian Sciences, about FDA action. A slightly edited version of the interview follows:
AJMC®: Can you explain how the antibody test works?
Hawkins: Our antibody test is actually a very simple, very fast test to look to see if your body has had an immune response to a prior COVID-19 infection. A small sample of blood is added to a little cassette. One drop of buffer is added through a little dropper bottle that looks sort of like an eye dropper bottle. And 10 minutes later, you look at the cassette and can see if you have M antibodies, G antibodies, or if you have both. Then there's also a line for control to make sure if you are negative for antibodies, you know that that test still worked.
AJMC®: Could you explain what the accuracy measurements mean—what do they mean to both a doctor and also to a patient or another layperson?
Hawkins: We use these words in diagnostics like sensitivity or specificity. The way to think about it is sensitivity is when the antibodies are there, how often do you detect them? And [with] specificity, it’s best to think about, when the antibodies are there, how often do you only pick up the right ones?
When I say, "you have something," did I pick up the right antibodies? I didn't pick up some other closely related sort of antibody….So when you look at our data, and we say we're 98.4% sensitive, it means when the antibodies [are] for COVID-19, or they're greater than 98% of the time, we're going to detect those antibodies. And then when you look at our specificity, which is 98.9%, so almost 99%, it means when we do tell you, "you have antibodies," there's a 1% chance—only a 1% chance—that we detected something that wasn't related to COVID-19.
AJMC®: So that's a very high level of accuracy for an easy, rapid turnaround test.
Hawkins: It is, I think. The other data that we are working with [in] a large academic medical center to publish compared this small sort of deployable test to a big lab based analyzer, and saw a very high concordance—over 98% agreement—between that large lab analyzer and this little test. So, that sort of speaks to the accuracy of it despite the simplicity.
AJMC®: Who should have a COVID-19 antibody test?
Hawkins: It’s a great question. There’s sort of a range of use cases that have evolved over the past few months of the pandemic. In the really early days, the predominant use was actually blood banks trying to help identify people who had been sick and recovered and could therefore donate plasma for use in treating really ill people, and that's still going on. Blood banks across the country are offering antibody testing to find those folks who can donate because that convalescent plasma continues to be a key part of a treatment regimen.
But more recently, you're seeing other utilization. One of the most common ones now, as you're hearing all this about asymptomatic spreaders or mild disease—one of the challenges is, if you don't have symptoms, you probably didn't go and get tested, or if you had a very mild case, since the symptoms of COVID-19 looks so similar to other respiratory infections, you may not have sought any test for the actual coronavirus, which means we might be way understating the number of people who are infected.
So, you're seeing public health, you're seeing the CDC, you're seeing large academic medical centers do these broad what are called zero prevalence studies to understand the actual rate of infection. I think the CDC most recently put out data in some of the big hotspots around the country that says the positivity rate may actually have been as much as 10-fold higher than what's reported.
As we move into businesses trying to reopen, you have frontline health care workers, you have workers in skilled nursing facilities, maybe in very high density areas where you can't get social distancing. So think of like some of the outbreaks we've seen in food processing and manufacturing and some of these areas, I think you're starting to see antibody testing, as a complement to the swabs and PCR [polymerase chain reaction] to plan out how they, how they manage those facilities…
AJMC®: And speaking to that, the intuitive idea would be that if you tested positive for the antibodies, you would have some measure of protection against COVID, at least for some time Do we know anything about how long the protection might last? Or how good the protection is?
Hawkins: This is the challenge in science, especially immunology. The way we get confident in other areas is time. But what we do know? So there are a lot of studies that have been reported, there are a lot of reports that are going to turn into [peer-reviewed literature]. I think one of the challenges is that the data are coming out even faster than it can go through the typical channels. What we're seeing is that people who are hospitalized are some of the first ones who were tested for antibodies. We have data on patients serially tested over the course of 3 months, and most of those people still have antibodies. There’s a recent study out of UCLA that even looked at people who had more mild cases. And they found that 2-and-a-half months later, people still had antibodies. But not everybody develops an antibody response. There's sort of a long host of reasons.
As an example, somebody we tested in our trial had was immunocompromised and was on immunosuppressive therapies. They didn't have an antibody response. Now, they’ve recovered, and were able to leave the hospital, but sort of intuitively, we wouldn't have expected them to have a response, and they didn't.
So, right now, the data say, the vast majority of people who recover do have a response and that it's still there. But the uncertainty is how long does it last?
And then the other part of your question is really, what level of protection do you get? So, right now we're not hearing widespread reports about people getting reinfected. It implies that if you have antibodies, you have some sort of protection. We're not seeing people sort of with 2 and 3 courses of the disease. But I think both of these questions can only be answered sort of over time, as we monitor and see how long do these respond, these antibodies remain?
We don't know the answers to these and really only time and monitoring is the way to answer that in in a scientific way.
AJMC®: Can you explain exactly what the emergency use authorization is, and how a person who thinks they might need to test can get access to it?
Hawkins: The Emergency Use Authorization is a way the FDA sets forth a set of standards for products to get to market. Those standards and reduced a bit from what they normally would be if you had to go through a formal process, what we call a 510 K or a PMA.…The emergency use is sort of a set of standards that are just meant for this, and for the longer term, the products will have to be converted to the full [pathway].
We've seen this before. In the US in 2009 we had H1N1, which many of us will remember.…There was an emergency use authorization process at that point. Over time, you will do additional work, because eventually the FDA will pull back the ability to have an emergency use authorization…
We're not the only antibody test provider; it's going to just like with other areas in this pandemic—it’s going to take a lot of companies to be successful. These tests are going to be made available through employers that will offer it routinely, through health care clinics, your primary care doctor, places like that. We're seeing public health facilities wanting to offer this type of testing, and even the drive-though clinics where a lot of people are getting swabbed and tested are beginning to offer these antibody tests as well. And obviously the large medical centers in major metropolitan areas have the ability to do this type of testing as well. So [people can access the test in] many of the normal places people would go to access health care, but we think with this simple test, we'll also start to see it in some of these sort of newer modalities that have popped up to support coronavirus, like the drive-through clinics.
AJMC®: And will this test be covered by insurance?
Hawkins: So far, we're seeing that insurances are covering these antibody tests. They have been from the beginning. If there's anything that has been that's historically been a roadblock to new technologies, whether diagnostics or therapeutics and healthcare, often the process of getting those things reimbursed is a very long process. In this in this pandemic, the insurance companies, both private and public payers like Medicare stepped up and right away started paying for testing. So, we're seeing widespread coverage of both the PCR testing that people have been getting, but also the antibody testing. We've seen we've seen coverage in both.
AJMC®: And if a person tests positive and it turns out that they have antibodies, should they get a vaccine in 1 or 2 years, when a vaccine is available?
Hawkins: I would certainly recommend that people do this. I will. I'm not antibody positive. I've tested myself in the development of the product, as you can imagine. But I think it goes back to my earlier feedback, which is we were fortunate that we're seeing people with, you know, antibodies here to 3 months removed from their recovery. We're fortunate that we're not seeing reports and studies coming out saying you can get reinfected. So, all those things are sort of good signs that you're getting some level of protection and that the protection is not just going away overnight. But because we don't know how long it lasts, because we don't know if its a true pure immunity—or if you could still get sick—people should still get vaccinated when the vaccines become available.
I think the real question will be, might antibody testing play a role in how we think about the rollout of the vaccine? Obviously if someone has antibodies, while we don't know if it [offers] 100% protection, and we certainly don't know if it's a lifetime, perhaps those folks can be deferred to a little later, and we can get the initial vaccine doses out to high-risk people, the people who don't have that protection. I think it could end up playing a role in that because it's hard to believe that, despite great efforts in the vaccine world, we're not going to instantly have hundreds and hundreds of millions of people able to get vaccinated—it’s going to take some time to do that. So, [an antibody test could] play a role in that. But at whenever it becomes available to me, I can assure you, I'll get the vaccine independent of whether I end up developing any antibodies from any exposure.