COVID-19 antibodies and antibody testing has come up multiple times this week in the office. Let us explore what an antibody is and how it interplays into our current knowledge of COVID-19. Let us briefly understand the two arms of the immune system to elucidate the role of antibodies. We have an innate immune system which is primal and composed of key initial defenses against an attacker (virus, bacteria, fungus, etc.). This includes everything from our skin barrier, mucus, acid in the stomach, and coughing to eliminate the perceived foreigner. Our immune cells may also start secreting interferon and interleukins (cytokines) which indiscriminately will attack the target, and in doing so, may harm our own cells in the process. It is considered a direct hand to hand combat. When one of the invaders is being seen for the first time by our protective white cells this type of blitzkrieg occurs and accounts for the inflammation and cytokine storm we have heard about in the gravely ill COVID patients. This flagrant inflammatory response is also responsible for the high fevers, muscle aches, and severe respiratory and gastric symptoms we may see in these infections. The body has mounted an forceful assault and it puts our bodies down for several days during this fight. This virus is new and not previously seen in our systems and will succumb to those who have a strong innate immune system. Let us remember who NOT is having many symptoms in this pandemic and who DOES have strong innate immunity. Infants and children are those at a great advantage because they have so many T-cells that have no memory of prior infections and therefore, are ready for battle. The cell-mediated (as opposed to antibody mediated) immune battle makes T-cells in the thymus which is quite prominent in infants and children. Those naïve T-cells are instantaneously ready for battle and get to the front line immediately. As we reach adulthood, the thymus no longer exists and most of our T-cells are mature and have memories of previous infections. Only a few of the new T-cell warriors are manufactured. Therefore, it takes us adults a much longer time for the innate immune system to kick in and fight a new virus.
The second arm of our immune system is the adaptive immune system which has a much more elaborate system of multiple types of white blood cells and multiple layers of processes involved to fight these same invaders. The immune system has developed a “memory” from a previous exposure to a specific pathogen and now has developed a series of steps to wipe out the infectious source. This system takes longer and now involves some helper T-cells, numerous other immune cells, and B-cells which make antibodies. Antibodies, which are protein-based, will go on a search and attack mission to chemically attach (in a lock and key fashion) to the foreigner. When this lock and key engagement occurs a whole cascade of events happens to kick in yet more types of cells to engulf and destroy this enemy. The adaptive immune system matures as we get older and some of the “memory” of this system is the reason we do not get some infections twice. Antibodies are coined “immunoglobulins” because of their protein composition. There are five types of antibodies (immunoglobulins, designated as “Ig”) including: IgA, IgD, IgE, IgM, IgG. For the purposes of this discussion, we will focus on IgM and IgG. IgM gets to the battlefield first. It is the largest of antibodies found in blood and lymph, and understandably it can get to the enemy quickly by nature of its transport system in the blood stream. IgM antibodies provide the early but only short-term protection in the infection. As IgG comes to the battle zone, the IgM antibodies will decline. IgG antibodies are smaller in size, but they provide a much more long-term protection against the pathogen. As our testing capabilities become more sophisticated, we can measure extremely specific antibodies to extremely specific infections. These details in types of antibodies can also help provide a timeline as to when the infection occurred.
This brings us to our current understanding of our diagnostics to help our treatment of COVID-19. Since this is a new virus and previously “unseen” in our immune systems, the innate immune system needs to be quite robust to contain the infection. When we are diagnosing whether a patient has the COVID infection, we are currently using an RNA assay which is directly measuring viral particles. RNA is the genetic code that this coronavirus uses to replicate, whereas some other viruses are DNA-based. The RNA detection of the virus itself is found in mucosal surfaces and nasal or throat swabs are used. The highest concentration of the virus is detected in the nasopharynx, so the nasal swabs are most accurate, but not all testing has 100% sensitivity. There are false positives and false negatives. There is more than one company making these assays. There is some variability in the techniques involved and there are different concentrations of the virus throughout the course of the infection. The higher viral load is in the beginning of the infection. Given all these possible variables it is easy to see why numbers may vary, and these numbers are continually being collected and analyzed through the CDC.
The antibody testing for COVID seems to be the most complicated for the public to understand. The antibody testing is also the most recent to come to the market during this pandemic. There is not great value in trying to use antibodies for the diagnosis since it may take up to two weeks into the infection to be able to measure the first (acute phase) IgM immunoglobulins. IgG antibodies, that provide the much more long-term protection, may appear 12 weeks after the infection. For those patients who do not feel ill and may want to know if they had an exposure, antibody testing can be done for that purpose. Keep in mind that the antibody information has fewer numbers since fewer patients have been tested for this. There has also been a limited time frame (the pandemic has not even lasted a year yet), such that even in current trials, there appears to be a small drop in picking up the antibodies the further away from the infection. I do caution, however, that this is preliminary data, and the testing sophistication will improve over time as well. Antibodies are the exact way that an immunization works so there is currently a feverish push to develop a vaccine which typically uses bit of the virus to stimulate our adaptive system to make specific antibodies against COVID-19. The extraction of the viral particles and the preservatives used should also be able to withstand vigorous safety trials before presentation to the public. And as I always warn my patients, this virus, as well as other cold viruses and influenza has the propensity to mutate. This mutation is a strategy to trick our immune systems to get in and bypass our adaptive immunity. If COVID-19 becomes “smart” and mutates every year, the antibodies we make to the vaccine may not be remarkably effective from year to year. Only time will tell. I believe that we are in our “last wave” of this virus because next season this virus will now meet the millions of patients who now have antibodies. The virus should be rendered less capable, and the body has a more direct approach to handle this virus. Stay safe and keep your immune system strong.