By Rashid A. Chotani & Syed S. Ashraf & Charlie Mize & Terry Clark
April 30 (UPI) -- Imagine yourself in one of these scenarios. First: you direct a food preparation and delivery service. You know that some of your employees have likely had COVID-19 in the past but many have not. Would it be safer to send out on delivery those who have recovered from infection and are no longer infectious? If so, how do you determine who they are?
Second: You are in charge of immigration and tourism for an island country. You would love to have visitors, but not those that are going to bring the virus back on shore. How can you prove that those entering are not infected? Or are immune to infection?
Last: You and your team of doctors and nurses need to treat highly contagious COVID-19 patients requiring life support. You know some of your team has likely had the infection and recovered. Would it be safer for the doctors and nurses who have recovered from infection to treat those who severely ill and contagious? And if so, how do you find them?
The solution to these problems and others like them is an "immunity passport," the demonstrated proof of immunity to SARS-CoV-2 by either recovery or vaccination. To find this proof, we need a test for both the virus and for immunity. The ideal test would be one that detected disease shortly after infection but before a patient became contagious -- and one that could demonstrate whether a patient had recovered from infection and was now immune.
There are several tests available for COVID-19 and in isolation all of them fall short of this ideal. However, we get much closer when we look at each test and fit them into a diagnostic framework built upon our growing understanding of the coronavirus and our immune response to it. What's more, joining different types of tests into a single approach provides us new insights into how COVID-19 behaves -- and how we can fight it.
The first available test and the test recommended by the Centers for Disease Control and Prevention and the World Health Organization is called Polymerase Chain Reaction testing. This testing -- also called antigen testing -- detects the virus' genetic code, or RNA, in a patient's nose or saliva. It is a simple concept and positive results are generally true.
But the test is far from perfect. It requires special training to perform, special equipment to process and exposes those conducting the test to the virus. Then there's the question of its accuracy. If we test too early or too late, the test can miss the virus. Perhaps the immune system has removed enough of the virus to make it hard to detect, or maybe the amount of virus during the days after infection is too low to detect.
Sometimes the test isn't performed just right and so the results are less accurate. When we receive a negative test, it isn't clear what to do. Is the test a true negative or an error? And if accurate, that negative does not tell us if a patient has been infected and recovered or if the patient has never been infected at all. Without that knowledge, it is impossible to know how much of the population has been infected and recovered, and if enough of the population is recovered to provide "herd immunity." Clearly, we need more than this PCR RNA testing if we are to move forward.
The other class of COVID-19 tests look for human antibodies to the coronavirus. Antibodies are proteins made by the human body to target and neutralize the virus. There are different types of antibodies, but most tests look for an antibody called IgM, which the body produces first, during active infection, and IgG, which the body creates later as part of a sustained, long-term immune response. These tests have the benefit of being easy to perform, fast, and in many cases can be more accurate than PCR RNA.
The human body builds more and more antibodies as infection continues, which means that antibody testing becomes more accurate as time passes, unlike PCR. There's also the ability to demonstrate immunity. In the case of many other infections, the identification of IgG in the blood indicates that a person is immune. For example, with varicella zoster, the virus that causes chickenpox and shingles, as well as measles, mumps, rubella and hepatitis A (just to name a few diseases) the detection of IgG antibodies is proof of immunity. In the case of COVID-19, it is very likely, but not yet proven, that IgG will similarly demonstrate immunity. We do not know how long that immunity will last, or whether the virus' mutations will allow it to escape the immune system, like influenza does. But the only way to know is to use these tests and study them.
Some have dismissed antibody testing as insufficiently accurate, with no role other than general population surveillance. They have deferred wholesale to antigen testing. The assumption of RT-PCR as being a "gold standard" must be clarified. PCR technology is well established, but PCR nasal or oral swab for COVID-19 diagnosis is new and authorized under emergency like the serologic antibody tests.
However, the ability of either test to predict disease will vary on the prevalence of COVID-19 in the community, no matter how it is conducted. Moreover, we have seen that testing for viral RNA alone has severe drawbacks -- a limited accuracy that can diminish over the course of illness and an inability to reveal anything about immune response.
Antibody response is also imperfect, but the caliber of antibody testing is improving, and when combined with RNA testing and clinical judgment, we can advance an understanding of the coronavirus impossible with the use of either test in isolation. But antibody testing is key. Only through a study of the body's antibody response and through continued use of antibody testing will we answer the important questions: Can we become immune? And can
we prove immunity through intelligent testing? The right solution under the present crisis is to gain as much insight so we can make better informed decision.
Dr. Rashid A. Chotani is an infectious disease epidemiologist and chief science officer at CareLife Medical. Dr. Syed S. Ashraf is a board-certified internist and managing partner at Carelife Medical. Dr. Charles Mize is the chief medical officer for U.S. health defense and is an emergency medicine specialist. Dr. Terry Clark is a general surgeon, Fulbright scholar, executive vice president and chief medical officer for Boston Biopharma.