Testing Explained Part II

Today we will discuss immune testing, for viruses in general and COVID-19 in particular.

Please understand that this is a novel virus. We know a lot less about it than we do about other viruses like Herpes, HIV, and hepatitis C. Anything that you read here is subject to modification as more research is done.

Viruses are not alive. They are strands of genetic material, either RNA or DNA, that are surrounded by a few proteins, as if the genetic material were wearing a raincoat. They become a problem when they find a host, or living organism, to help them reproduce, or make more copies of themselves. In order to succeed in their quest, they need to be able to anchor themselves to a host cell and convince that cell to allow them access inside. Once inside the cell, they find their way to the nucleus, where the host’s DNA is. They have ways to order that host DNA to make thousands of copies of themselves. Once that host cell dies as a result of this invasion, virus material spills out in search of more cells to invade. Rinse and repeat; a successful virus (say HIV) can boast of hundreds of thousands of copies in a few drops of host blood.

Our immune systems are in constant alert for these invasions. As I said yesterday, the innate immune system starts the process of virus rejection almost immediately. It takes a week to ten days for the adaptive immune system (antibodies) to direct a full-blown response to try to destroy the virus.

Once the little pieces of virus are expressed on the surface of an immune cell, other immune cells make antibodies against these pieces. We don’t make one antibody: we make dozens, for as many pieces as there are; sometimes more than one antibody per piece.

Through a complicated process which is not completely understood, our bodies learn, within a day or two, which antibodies are better at finding loose virus pieces (avidity) and sticking tightly once they are bound (affinity). At this point, the cells that make the weaker antibodies are told to kill themselves (they shrivel up into nothing; this is called apoptosis). The more efficient cells are ordered to have millions of babies that have the same capability that they have. If all goes well, the virus has no chance.
There are two main classes of antibodies that are used to combat viruses. IgM is the first responder and usually disappears within a few weeks. IgG takes a week or longer to take over, but is much longer lasting, many times for a lifetime. Once IgG has killed most of the virus copies, the cells that make IgG are told to kill themselves by apoptosis. A few, maybe as few as one or two, are spared. They are called memory cells. They hide deep within our lymph glands and spleen. They are called upon if the virus tries another attack in the future, thus making it less likely that the virus will make us sick the second time around.

The immune tests that you hear about on TV measure IgG and IgM that is directed against the Covid virus.

If anti-Covid IgM is detected, that means that the infection was fairly recent. IgG presence indicates that it has been a few weeks (or months, or years) since you were ill. The problem is: as you remember, dozens of antibodies are made as an initial response to the virus. There is not one antibody. Testing must be able to detect at least a few of the anti-Covid antibodies. There is another problem. Covid is a Corona virus (nothing to do with the beer). Corona viruses are responsible for at least 20% of common colds. People who have had a common cold (all of us?) will have Corona virus antibodies in their system. A test must be able to distinguish the IgG directed against the common cold from IgG made against Covid. Otherwise all of us would test positive, which would cause significant panic, and trigger numerous public health measures that would be unnecessary.

Many immune tests have been developed in response to our public health emergency. Most of them fall into one of two categories. The point-of-care (POC) test is performed by a small machine that is easy to use, inexpensive, and does not require much technical expertise. It runs on a drop of blood. It can be easily deployed to rural locations and doctors’ offices. Their reliability for measuring Covid antibodies is open to question. The second kind is the ELISA test. This usually requires a blood draw and sophisticated machinery only available at reference labs. These are close to 100% accurate.

When the magnitude of the epidemic became clear, our FDA decided to waive many of the requirements that are used to allow marketing of the test. It allowed manufacturers to “validate” tests by themselves, and it took their word for it when they swore that their test was accurate.

What do you think happened next? You only get one try at an answer.

Right! Close to one hundred tests flooded the market. Almost all of them were POC tests, that many times could be run on machines that we already had. Most were made in China. They were not too expensive. Unfortunately, a majority measured IgG that had nothing to do with Covid, and many failed to detect anti-Covid IgG. Spain bought thousands of these, and their errant results are part of the reason that that country has been so adversely affected.

Tomorrow we will go into further detail on ELISA tests and our response to the need for them.