What We Think We Know about Immunity for SARS-CoV-2 – How I would explain it to a Fifth Grader

Some physicians have been pushing for people to get antibody tests for COVID in ways that I believe have been irresponsible. Recently, I commented on twitter (@drpatesblog) on yet another case, in which a patient with documented COVID infection was tested for antibodies 40 days following the resolution of his illness, and antibodies were not detectable. One of my followers, an elementary school teacher, asked if I could explain immunity to SARS-CoV-2, the virus that causes COVID, as if she was a kindergartner. I thought about how difficult that would be, but how many people this would help understand these complex concepts if I could. I decided that I couldn’t get it down to a kindergartner level, but perhaps I could explain it at a 5^th or 6^th grade level. Here is how I did.

The immune system is actually very complex. Most often, people equate antibodies with immunity to something, but antibodies are just one part of a very complicated system, and having antibodies to something doesn’t always mean you are immune to it. So, hear is what we know about the immune response to SARS-CoV-2 for a 5^th or 6^th grader:

If a bacteria or virus invades your body, and you have never been exposed to that invader before, the first response of your body is to send in ground troops that will try to stop these invaders at your border (your skin or just under your skin if you get cut, or your nose and throat if it is trying to invade your body there, or your gut, if it is trying to make entry there).

The ground troops with their rifles are called white blood cells (or white cells), and they don’t care who the enemy is, they just attack and try to shoot anyone (in this case a bacteria or virus) who doesn’t have the same uniform as the rest of the body (in this case, features that these white cells recognize as being your own body as opposed to an invader).

Just like we have different military forces (Army, Marines, Navy, Air Force, National Guard, etc.) and they all have slightly different roles and tactics to attack an enemy, we have many different types of white cells in our blood, and they each conduct different kinds of warfare against these bacteria and viruses.

Just like our ground troops can throw a hand grenade or fire a cannon and blow up our enemies as well as things around them that we might otherwise not want blown up (like innocent bystanders or buildings, etc.), our white cells start releasing chemical warfare against these invaders of our bodies and they cause some indiscriminate inflammation and surrounding tissue damage, as well, but as an attempt to kill these invaders or at least slow them down.

What our ground troops (white cells) are trying to do is prevent these invaders, in this case a virus, from crossing that boarder (our nasal passages and throat in the case of SARS-CoV-2) and entering into our towns and cities (in this case our cells), where they an take over our food supplies and manufacturing plants that will allow them to make more invaders (viruses) that can then increase their attack on us.

This chemical attack is what makes us feel bad – fever, aches, cough, runny nose, etc.

Now, all this time that our ground troops (white cells) are fighting the invaders (virus) off at our borders with their rifles, hand grenades and cannons, they have already sent the message back to headquarters that we have invaders, a sample of what they look like, and a request that we need some weapons that will specifically target these invaders to stop them before they get into our towns and cities (cells) where they will make more invaders (virus). These weapons will be very specifically targeted to this invader so that they only kill the invader and don’t cause all the collateral damage (destruction of property and injury or death to our own body’s cells and tissues as friendly fire).

HQ then revs up the manufacturing plant and starts making these highly targeted bombs (antibodies) that recognize something that is different that makes up these invaders that is not present in our normal body cells and tissues. This different thing is called an antigen and HQ manufactures these special bombs (antibodies) that only blow up anything that has that particular antigen and leaves everything else alone. It ordinarily takes HQ 7-14 days to make these specialized bombs (antibodies).

In the meantime, our ground troops (white cells) have to hold off the invaders. Sometimes they do, but often times, some of the invaders get into our towns and take over the food supply and start manufacturing new viruses.

Now, if you get an antibody test while you are sick but before HQ has had time to make antibodies, the test will be negative, even though you are infected. This is called a false negative. It is also possible that you had some left over antibodies from a prior invader, but you already defeated that invader, but the antibody test identifies those antibodies as antibodies to this virus because they look a lot alike, even though the antibodies it is recognizing don’t work against this new invader, or don’t work very well. This is called a false positive – the test is telling you that you have the antibodies when these are not the antibodies we are looking for. Unfortunately, that can make someone hang out with someone in close contact who has these invaders because the person thinks they are protected, but these invaders move from the infected person to you and now you become infected.

Now, these bombs (antibodies) come in a number of different kinds. Antibodies do often defeat invaders, but not always. We have examples of other virus invaders where HQ makes plenty of antibodies, but the invaders march on and take over our cities and don’t seem to be slowed down by the antibodies. In the case of this coronavirus, we think antibodies are important, but we don’t know yet. This is a reason to save your money and don’t get an antibody test.

Now, back to the types of bombs (antibodies). It turns out that you need one kind of antibody if the invader is crossing the skin (IgG) and you likely need a different antibody (IgA) if the invader is crossing a mucosal border (your nose or gut). Polio was a gut invader. We developed two different vaccines – a shot and a sugar cube, and it turned out that the sugar cube worked the best, because it caused HQ to make IgA better than the shot did. Everyone talks about IgG and that is what the antibody tests check for, but it may be that IgA is equally or more important – we don’t know. The good news is that in one of the first vaccine trials to be reported, it appears that the vaccine does stimulate a robust response of both IgG and IgA.

Okay, back to the types of bombs HQ is making. In addition to different types of antibodies like IgG and IgA (and there are others), some of these bombs are really powerful killer bombs called neutralizing antibodies, because in a test tube, they keep the enemy from entering into our towns and cities (cells), and if the invaders can’t get into our cells, they can’t make more invaders, so, when we shoot or bomb all of the invaders at our borders, its over because there are no more invaders.

In this regard, recent studies have been disappointing. Of those who have been infected, it appears that only 1 – 10 percent of these people make neutralizing antibodies in levels that based on other infections, we would guess that these would be clearly effective against this virus. Let me add that we don’t know that an antibody is truly a neutralizing antibody in someone’s body just because it is in a test tube. And, we don’t know how important neutralizing antibodies are in the immune response to SARS-CoV-2 (there are other examples of viruses that induce lots of neutralizing antibodies to be produced, yet they don’t slow or stop the infection).

So, if not everyone is making neutralizing antibodies or enough neutralizing antibodies, then what are they making? Well, it turns out that some of these other bombs (antibodies) are like paint balls/pellets, where you shoot the invader and it doesn’t kill them, but they are now marked. Marking these invaders can help other parts of our immune system go after them. This other part of the immune system is called the cellular immune system.

In this case, HQ is not only making highly specific bombs (antibodies – for extra credit, this part of the immune system is called humoral immunity and for credit to skip a grade, that part of the immune system with our troops on the ground at our borders is called innate immunity. It is innate because we are born with it and it does not require ever having been exposed to something to fight it. It is ready to fire on sight), but also highly specialized tanks (T-cells).

Remember, the humoral immunity – antibodies – takes time if you have never been exposed to that invader before. We have to get the body part to HQ, HQ has to design a blueprint for the bombs, and then we have to manufacture the bombs (antibodies) and that all takes about 7 – 14 days.

A recent report showed that a patient who was infected and recovered, but even 40 days after recovering still had not made measurable levels of bombs (antibodies). And, we have seen that in various studies, anywhere from 2 – 16 percent of people who were invaded (infected) did not make bombs (antibodies) that were targeted to this invader (coronavirus), at least not in levels we could measure. So, these people would be said to have a false negative test – in other words, they were infected, but have a negative antibody test. Now, if that was not disappointing enough, we also found in recent studies that if you did make bombs (antibodies), which the vast majority of those who were invaded do, HQ appears to decrease production in much shorter period of time than we had hoped. We would like HQ to keep making the bombs in case, once defeated by our body, the virus is planning to attack us again this fall or next winter. Unfortunately, in 13 percent of those who were symptomatic and 40 percent of those who were asymptomatic, bomb levels dropped to a level that most of our tests could not detect after just 2 – 3 months.

So, what does this all mean? First, we don’t know how important antibodies are in the fight against coronavirus and to our immunity against reinfection. If they are important, then these studies are bad news.

But, since most people are getting over the virus without measurable antibody or with low levels of antibodies, my guess is that another branch of the immune response (cellular immunity) may turn out to be far more important. Before I turn to cellular immunity, let me conclude on antibodies.

Don’t waste your money on an antibody test. Whether it is positive or negative, we have little idea of what either means. And, even if positive, you cannot assume you are immune. You must continue to use precautions. These antibody studies give us little confidence that you will be immune this fall/winter if you did get infected during the first spike of cases back in March/April, if antibodies are important to the immune response.

So, now, lets get to the good news – cellular immunity and vaccines. So, while HQ is mass producing bombs (antibodies), they have also been producing highly specialized tanks (T-cells).

These specialized tanks (T-cells) also come in several types. As, I mentioned previously, the goals of our innate immune system (our troops at the border) is to kill the invaders, or at least hold the invaders from getting to our towns and cities (our cells, where they can take over our manufacturing plants and make more invaders) until HQ has time to produce the specialized bombs (antibodies). Once an invader gets into a city, our innate immune system is not very effective and our specialized bombs (antibodies) generally can’t get inside to capture the invaders. It’s like ISIS getting into a town or city where they can create a stronghold and many barriers of protection as opposed to being out in the open in the unoccupied land by our borders.

So, HQ makes these T-cell tanks while they are making the antibodies. One of these tanks has the ability to find pieces of the invaders and it amplifies the attack in those areas (helper T-cells). Another type of tank can identify which towns or cities (our cells) have been invaded, and while our antibodies can’t penetrate the invader’s hold on the towns, these tanks just blow up the cell and kills all the invaders who are occupying the town (our cells) (these are called cytotoxic or killer T-cells). And, thinking ahead, HQ makes tanks with advanced radar, infrared detection capabilities and other abilities to quickly detect these same invaders again should they ever try to cross our border again once we have defeated them (memory T-cells). The long-lasting antibodies and the helper and memory T-cells are useful, because while the first time we face an invader, the entire range of our arsenal (humoral- antibodies- and cellular – T-cells) takes 7 – 14 days to mount our full response, the next time we see the invader, all of these parts of our immune response can be called to duty almost immediately, so much so, that we often will not get sick or have any symptoms, or if we do, with some unusual exceptions (like Dengue fever), we will only have a mild case.

What we also found out in these recent studies, is that while the antibody response to SARS-Co-V-2 was not particularly encouraging, the cellular response in nearly everyone was. Not only did those who did not mount a very good antibody response develop a good cellular response, but even family members who lived with someone who was infected, but to the best of our knowledge, did not get infected themselves, still developed a good cellular immune response! And, for many viruses, we know that the cellular immune response tends to be more important for viruses, because there are diseases that you don’t produce antibodies, and these patients tend to get serious bacterial infections, but not severe viral illnesses; while there are other diseases for which patients have problems with their T-cells and they tend to get bad and prolonged viral infections, like shingles that will occur in multiple locations (whereas shingles tends to occur only in a single area in those with otherwise healthy immune systems).

Vaccines can often be engineered to trigger specific antibody responses that we want (like neutralizing antibodies against a specific part of the virus that appear to be especially protective against viruses getting into cells), but they also often trigger the cellular immune response. Even if the antibody response declines over a few months, we have many examples (e.g., measles) where the memory cells specific for that virus can persist for many decades, if not the remainder of your life.

So, to sum up:

1. Don’t get an antibody test – we have little idea what it means (and avoid those who push these tests or claim to be able to tell you what it means).
2. If you think you had COVID earlier in the year, but didn’t get tested, you probably didn’t (only about 8 percent of such individuals appeared to have actually had COVID), and even if you did, we don’t know whether you could get infected again this fall, so take all precautions.
3. While results from antibody studies have been disappointing, results of cellular immunity are quite good and we have very good reason to be hopeful and optimistic about current vaccines under development and testing.
4. In the meantime, the key to slowing the transmission of this virus is putting distance between those who are infected with and shedding the virus and those who are susceptible (and everyone should assume that they are susceptible).
5. Since we don’t know who is infected and may be shedding the virus (because they may not feel sick yet), if you have to be in proximity to other people, the best option to reduce your chances of getting infected is for EVERYONE to wear a mask. The added benefit is that the same infection control practices for coronavirus are likely to slow down or prevent the spread of other respiratory and influenza viruses that we are likely to encounter this fall.

This is now the point where I apologize to all the fifth and sixth grade teachers for thinking I could teach something as well as they do and to all the immunologists out there for the liberties I took in trying to explain this very complicated matter.