Note: While this article is not specifically about systemic sclerosis, since there is a lot of interest currently about when people can safely resume normal activities in the midst of the COVID-19 pandemic, we thought that this article might be of interest to many of you. This article is based on a story that was first broadcast on April 15, 2020 on National Public Radio (NPR). You can read the original story here: COVID-19 Antibody Tests Can Miss the Mark.
When people get infected with a virus such as influenza or a cold virus and eventually recover from that infection, their body produces antibodies that for a time are protective against that exact same virus and often to some extent similar viruses. How long and to what degree these antibodies protect people from re-infection with the same virus varies widely, in part due to how much of the virus they were initially exposed to. For example, if you were initially exposed to a minimal amount of the virus, you might develop fewer antibodies than someone who survives after being exposed to a much larger amount of the virus. We don’t know about COVID-19 antibodies yet, but it is possible that immunity might be similar to that seen in other corona viruses such as SARS or milder forms that result in symptoms seen in a common cold.
It is reasonable to assume that if you develop a COVID-19 infection and fight it off, you would then have some immunity that could be very helpful. For example, if could be very helpful to know which front-line medical personnel are immune or partially immune to COVID-19 infection. Also, once someone knows that they are immune to the virus (and also not currently positive for the virus – see below), they could return to work and help to rebuild the economy more rapidly.
Within the past few weeks, a number of companies have announced that they have developed tests that can detect antibodies to COVID-19 in a drop of blood. The FDA is allowing these tests to be marketed without independently verifying their accuracy. As of today’s date (4/15/20), only one rapid antibody test has been FDA approved, but even that test lacks FDA accuracy verification. These first-generation tests are designated for research purposes only currently; however, in some cases people are able to get access to antibody test kits on an individual basis.
There is no question that having tests that can determine if someone has antibodies to COVID-19 is a very important advance in the battle against this disease. But it is very important for people to understand that if you test positive for COVID-19 antibodies with one of these tests, it is NOT the case that you can safely go back to work and resume your pre-pandemic life.
Here is why.
One of the key measures for how accurate a test is called “specificity”. What this means is simple: if you get a positive result, what is the chance that the result is a “false” positive? In the case of a COVID-19 antibody test, what is the chance that if you get a positive result, you actually DON’T have the antibodies. Preliminary reports suggest that several of these tests are about 90% to 95% accurate, meaning that between 5% and 10% of the time, a positive test result is false and you don’t actually have the antibodies.
On the surface, being correct 90% to 95% of the time sounds like this is a very good test, but as the NPR article explains, that is not the case at all, especially on an individual basis. Here is a simple example. Suppose you test 100 people for COVID-19 antibodies and 5 actually do have these antibodies. If the test is 95% accurate (5% false positive error rate), then out of the 100 people tested, you will get (on average) 10 positive results! This doesn’t sound correct, but it actually is. Since the test is 95% accurate it will almost certainly find the 5 people that actually have the antibody. But, out of the other 95 people tested, about 5 will also falsely test positive. If you decide to go back to you pre-pandemic activities because you tested positive, then there is a 50-50 chance that you actually don’t have the antibodies and you are completely vulnerable to being infected. In reality, if you are in that group of five people with a false positive antibody result, psychological research suggests that you will probably be more likely to get infected by the virus since you will assume you are immune and as a result will be less likely to observe key safety steps such as social distancing and even frequent hand washing.
OK, so an accuracy rate of 95% isn’t that good at all. So what would happen if you got tested at two different labs using two independently developed COVID-19 antibody tests? If the 5% false positive error rate is entirely random testing error, if you tested positive at two different labs, instead of the test being 95% accurate, the combination of two independent tests would now be about 99.75% accurate. To find out of this is indeed the case, I consulted with an immunology professor with a 47-year experience in the area of immunotherapy, immunoassays, immunoregulation and immunobiology of HIV and SARS infections. Unfortunately, it turns out that in many cases, the 5% false positive error rate is not just a testing precision issue, but it is caused by the presence of various cross-reacting antibodies other than the infectious agent, for example from a previous infection of a different corona virus. This cross-reaction also can occur in people with autoimmune diseases. In these cases, you would be likely to get a false positive result from both labs, unfortunately.
The second problem with deciding that a positive antibody test means you are safe to resume your normal activities is that having antibodies does not at all mean that you are virus free. When people start to develop the antibodies to COVID-19, they may have absolutely no symptoms at all. In other cases, they may have severe symptoms and be hospitalized. However, in both of these cases, they are still highly infectious. One of the biggest unanswered questions is how long you are infectious after you “recover” from COVID-19 and are now symptom free. We do know that there are a few reports of people still being positive for the virus long after they became symptom free.
So what does this mean in practice? Until we are able to:
- understand fully the significance of actually being antibody positive, e.g., does a higher antibody level give you more protection from being re-infected,
- have an antibody test that is MUCH more reliable than these first generation antibody tests, and
- be able to quickly and accurately determine if someone has the virus and can still infect others,
returning to pre-pandemic activities will remain very risky, especially if you are older than 60, immunosuppressed, or have an underlying medical condition that puts you at increased risk for major COVID-19 complications.