Who Should Get a COVID-19 Antibody Test?
Earlier this week, I received my 7,000th email from someone questioning whether the antibody test we are offering is reliable. Maybe I am exaggerating a little, but I’ve had A LOT of emails and phone calls from people who believe that they have had and recovered from COVID-19 and are looking for confirmation. If you watch any three news shows on any given day, you will see at least four different stories about antibody testing, and many of them create more questions then they answer.
This particular email was from a gentleman that was certain he had the virus; he was asking when or if we would offer one of the four tests that had been granted an Emergency Use Authorization (EUA) from the FDA because he wanted a “more reliable test.”
Here is the email I sent in response:
Thanks for your email.
The short answer is: I have not made any progress engaging with any of the four tests that had been granted an EUA by the FDA.
The longer answer is that I do not believe I would be giving my clients a leg up by doing so.
Please forgive me if you already know all this, I want to be as thorough as possible.
In relation to antibody testing for COVID-19, the FDA has three categories:
FDA Policy on Diagnostic Tests during the COVID-19 Emergency – This covers all testing that has not yet achieved either of the other two categories. In order to be used, these laboratories or manufacturers need to have registered with the FDA. Testing can only be performed in high complexity CLIA laboratories. Our clinic has a CLIA waiver, but we are not designated as Medium Complexity or High Complexity, so we cannot perform the tests ourselves, we must send the samples to a laboratory that is high complexity. The current laboratory we are using is Access Medical Labs (AML), and they have this designation. For the record, AML has applied for an EUA for the testing they are doing.
Emergency Use Authorization (EUA) – Cellex (4/1), Ortho Clinical Diagnostics, Inc. (4/14), Chembio Diagnostic System, Inc (4/15), and Mount Sinai Laboratory (4/15) have all received their EUAs. The first three are authorized for Medium and High Complexity labs, and Mount Sinai for High Complexity. It is my belief that these labs were the first to submit and get the paperwork done correctly (notwithstanding any political help they may have received), not that the FDA believes their tests to be better or higher quality than others that are still running under the FDA Policy. More on this in the next paragraph.
FDA Approved – To date, no serology tests have achieved this, and it will most likely be quite some time before any do.
Next has to do with the accuracy of Serology testing. This consists of four factors:
Sensitivity and specificity. These two measures refer to the ability of a test to detect a true positive sensitivity and the ability of a test to detect a true negative, specificity. None of the tests on the market even begin to claim 100% in both cases for either antibody. Some claim 100% for one or the other with a single antibody. The tests that are being run under the FDA policy and EUA are similar in sensitivity and specificity. The fact is that serology testing is not an exact science. False positives can also be triggered by other antigens, although that is rare.
Time of the sample being tested in relation to infection. Early on in infection, your body is manufacturing IgM, but that IgM is actively fighting the antigens and is being consumed at a rate equal to or faster than your body is creating them. It is only in the later stages where there is ‘free’ IgM in your blood, where it will begin to show as positive in a qualitative test. Early on, infections will most likely test negative for IgM. IgM can also show long after the infection has been defeated, and no virus remains in the body.
Everyone is different – While most people react similarly to infections, no two people react the exact same way. Different people produce different levels of antibodies at various times during infection. Therefore, you see people with weaker immune systems more likely to have severe symptoms. Some people with hyperactive immunity will often not even show symptoms or have very mild symptoms. Some people are incapable of producing antibodies at all.
Human error in testing – Instant, cassette-based tests are subject to human error, both in the way the test is run as well in the way the test is read. The technician can put too much or too little blood in the cassette, or they could do the same with the reagent, either of which can cause a misread. Laboratory testing on automated equipment eliminates most of the potential for human error.
I am confident in the machines and reagents used by Access Medical Labs. They have the data based on the number of samples they have run, and that information is included in their request for an EUA. When their EUA is granted, it will not make them any more or any less accurate. I would also love to be able to be doing CLIA waived instant tests in our clinic because they are much less expensive, and the results come much faster. We continue to seek out a manufacturer that will be granted a CLIA Waived EUA for a Point of Care Test (POCT). Our technicians are trained in how to administer and read these tests, which I believe will lower (not eliminate) the chance of human error.
Either way, lab-based or POCT, we will, unfortunately, report some false positives and some false negatives; it is a fact of life in serology testing. That is why we caution our patients to consult their primary care physician, especially when testing positive for either antibody. Serology tests by themselves cannot definitively say whether you are infected, have been infected, or have not been infected. For a single patient, it can provide data that they can use in conjunction with the direction of their primary care physician to build a plan on how to best mitigate their chances of being stricken by coronavirus. Of equal importance is the amount of data being gathered to help local health departments and the CDC in their mapping of the infections, and efficiency and efficacy of plans to combat it and future pandemics.
We have run just under 200 tests in the past ten days. About 80% of the people we have tested have had similar stories of having fallen ill with COVID-19 like symptoms in January, February, and March. Many received negative flu tests at the time. Many had been traveling overseas, in California, and/or New York. Most of the positives we have received have been those that have traveled.
While I know it is only anecdotal, our first positive came from a close family friend. My goddaughter lives in NYC and was there when things started blowing up. She managed to get a flight to Austin on March 17th and moved in with her parents and her brother. Her parents and brother were naturally concerned that they might be getting exposed and were quite spooked when two days after returning home, she lost her sense of taste and sense of smell. At that point, she quarantined herself in her room, and the family went from being very cautious about washing and disinfecting to being fanatical about it. Those were her only symptoms, and they went away in two days. She is a very fit, 23-year-old girl, so it appears her body did a great job of fighting the infection off. We tested her three weeks after her symptoms had disappeared, and she showed positive for IgM and IgG. No one else in the family was positive for either antibody. We tested her again the following week, and she was still positive for both antibodies, but the IgM indicator was much fainter then it had been on her first test. Both were with the POCT kit. She is due to come in for a blood draw tomorrow, which will be sent to the lab. I am hopeful that she’ll come back as only IgG positive. Regardless, I will still recommend she shares the results with her own doctor and follow his advice, as well as continue to be cautious of hygiene and maintain social distancing so as not to pick up the virus on her hands or clothes and inadvertently transfer it to someone else.
I’m sorry for the long-winded email; I just want to share as much as I know to help dispel some of the misunderstanding and misinformation that is floating around.
If we arrive at a point when we have a test available that is on the EUA list, I will let you know, and you are welcome to come in. I can assure you that when that time comes, my confidence in that test will be the same as the one we are offering now.
I truly hope that you have had and fully recovered from coronavirus with ongoing immunity, and wish I had the tools that could give you 100% confidence that it is so. The sad fact is that I don’t, and at this point, no one else does either.
President, ARCpoint Labs of Austin North
Photo Credit: Getty Images / Ridofranz