As we rapidly approach the end of a second month of staying home, some parts of the country are beginning to ease their restrictions. Even in New York, there is some discussion about doing similarly. That being said, there is little new guidance to offer as to exactly when or how this concludes since the last communication we posted. Today, we plan to give a quick primer on a couple of concepts that are thrown around on media outlets to help understand some of the complicating factors regarding viral infections and immunity that face those trying to decide how to progress.
Every day we hear about a need for increased “testing for coronavirus.” Testing for a virus can mean one of a couple of things:
- Testing for evidence of viral infection
- Testing for evidence of actual infectious virus
The two concepts sound similar, but they are very different. Currently the testing being performed falls into the category of testing for evidence of viral infection. Using a nasopharyngeal swab (aka pipe cleaner up your nose far enough to scrape the back of your throat) a sample is obtained for testing. The test itself uses a technique known as RT-PCR to amplify viral genetic material. A positive test indicates that some viral RNA (genetic material) was present on the swab. What the test does not tell you is whether the infection is still active or if the individual is still contagious.
Testing for evidence of actual infectious virus is not typically done. What this would require is obtaining a specimen and then growing the virus in a culture. If you were able to grow virus from the specimen you would know that there was infectious virus in the sample.
How does this pertain to what is being performed? Lots of individuals can swab positive for presence of viral infection for quite some time after they are no longer contagious. That is their swab tested using RT-PCR is positive for presence of viral RNA, but had you attempted to culture virus, you would fail to be successful.
As a secondary confounder, it is worth noting that any test is only as good as the sample obtained. A poor sample can lead to a false negative test. This means you can have actual infectious virus, but not be able to detect any evidence of such.
Main point of this discussion is that while these tests are nice tools, they are far from perfect in making global decisions. Currently however, they are the best tools at our disposal.
There is also a ton of chatter about antibody testing and proof of immunity. At this time there is no such test. There are numerous reasons for this. First, antibody tests are at best a proxy for immunity. What they technically tell you is that the individual has antibodies that interact or bind to some part of the virus. What they do not tell you is whether that is relevant.
- It is possible for someone to have “cross-reacting” antibodies. This means antibodies the individual generated to something else that happens to interact with COVID 19 in this case. Most commonly this is from prior infection with non-COVID coronavirus, but could be from completely unrelated reasons where part of some other entity happened to look similar to the body to COVID.
- When they discuss “specificity” this is what they are getting at. A test that is 95% specific indicates that when a test is positive it really is 95% of the time. The other 5% could be giving a positive result for the reasons mentioned above. Most of the tests that are currently available do not have data demonstrating they are specific for the current COVID virus. To this point, the labs have disclaimers on their website stating their tests are being used under the EUA (Emergency Use Authorization) and may lead to false positives due to picking up exposure to other types of coronavirus.
- It is possible to have identified antibodies that are very specific for COVID and still irrelevant for presence of immunity. When the body generates antibodies to a virus, it could be to any part of the virus. The only ones that are relevant for immunity are the antibodies that would protect from the virus causing infection.
- As an example, if you were to solder a ball bearing to a key near the top where you would loop it to the keyring so that you could identify it was for your front door, the key could still be placed in the lock and function as intended. However, if you soldered the ball bearing to the end of the key, it would prevent it from being placed in the lock render it useless. Antibodies that render immunity are known as “neutralizing” antibodies. They work similar to the latter key example. They bind the virus in such a manner that it prevents it from binding to the receptor that pulls it into your cells.
- Without going off the deep end with a lesson in immunology, it is also worth noting that you can have non-antibody related immunity. Your body has different types of immune responses. Antibodies are made by B-lymphocytes. They require assistance from CD4+ T lymphocytes to do so. Some infections are primarily fought off using CD8+ T lymphocytes, a mechanism known as “cell mediated response.” Other infections require significant components of both responses.
- Both B-lymphocytes and T-lymphocytes are capable of converting to “memory cells” after infection, and these are required to have long term immunity.
- The duration by which these “memory cells” impart long-term immunity is variable.
So, in a nutshell we have tests that are limited at this time to denote who is contagious, and we have nothing to show whether someone is immune. Even should they validate the current antibody tests to show they detect have been exposed to COVID, they do not at this time have any real bearing on whether that person is actually immune to COVID. While most are inclined to think that immunity is generated when recovering from infection, that is not necessarily a given and is one of the major focuses of the ongoing research regarding this viral infection.