You’ve probably seen stories like this as well, of people who get SARS-COV-2 and start showing AIDS-like symptoms. You can be skeptical when you see the middle-class white women with thick black rimmed glasses complaining about their health problems, but guys like this are more inclined to deny health problems than to invent them. I want to explain in this post what I believe is happening. Why are people getting AIDS-like symptoms?
To start with, I want to illustrate again, the race between SARS-COV-2 and the human immune system. We have an antibody response against SARS-COV-2, from natural infections and from vaccines. There are different antibodies, some are neutralizing, they’re able to stop SARS-COV-2 from productively infecting a cell, others are binding, they bind to the virus but can’t stop it from infecting a cell.
Different antibodies differ in their capacity for neutralization. As versions of the virus have to spread through a population with some immunity, they will generally mutate in ways that allow them to avoid the most neutralizing antibodies we deploy. The first Omicron versions are a good example. Infection then causes your body to deploy an immune response characterized more by sub-neutralizing and binding antibodies, as the previously most neutralizing antibodies now no longer neutralize. You’ll still fight off the virus, but you’ll be worse at it. Eventually versions emerge that avoid more of those sub-neutralizing antibodies too, until eventually you’re left with versions like XBB and BQ.1.1, where all the neutralizing potential of our antibody response seems to be gone.
So what happens then? Well, antibodies perform different functions, even just the non-neutralizing binding antibodies can perform useful tasks under the right circumstances. But generally speaking, it’s a bad thing for you to recall an antibody response against this virus that is non-neutralizing. There is such a thing known as antibody dependent enhancement, you have probably heard a lot about it by now.
The problem with antibody dependent enhancement is that it takes on many different forms. Everytime we’ve seen it happen in a disease, it functions in a different manner. Take a look with me at an excerpt from a Japanese study that I read a while ago:
Recent studies have demonstrated several mechanisms leading to ADE, which can be FcR-dependent but ACE2-independent, FcR-independent but ACE2-dependent, S-protein conformational change-dependent, or both FcR- and ACE2-dependent ADE12,23,24,25,30.
There are many different ways for our antibodies to help out SARS-COV-2 in its goal of producing more copies of itself. I want to take a look with you at what this FcR-dependent form of antibody dependent enhancement looks like.
To start with, the Fc receptor is a receptor often found on the surface of some of white blood cells. It’s a receptor that manages to bind to the tail region of an antibody, called the fragment crystallizable region, hence why the receptor is called the Fc receptor. Whereas the parts that bind to pathogens always differ a lot, the tail region is identical within a particular species of antibody.
This Fc receptor binds to an antibody’s tail, so that these white blood cells of your body can do their job. When it binds to the phagocyte for example, the phagocyte gobbles up the viral particle and can performs phagocytosis, that is, destroy the viral particle. In the absence of the antibodies the cell wall would repulse the viral particle, but when coated with these antibodies the phagocyte can let it in.
There are different types of phagocytes, including the monocytes, macrophages, neutrophils, tissue dendritic cells, and mast cells. Their job is to “eat” viral particles. When the viral particle enters these pahgocytes, a phagosome is supposed to form around them, which is a protective coating made from the cell’s membrane. This phagosome then fuses with the cell’s lysosome, which is basically the equivalent of a big combustion chamber where everything is broken down so it can be recycled.
Of course as a white blood cell, a phagocyte also has a cell nucleus and all the genetic material necessary to replicate. And that’s where the problem comes in, as there will inevitably emerge microbes that figure out how to escape the combustion chamber. This can mean two things: Perhaps the microbe just sticks around and screws up the white blood cell, damaging the cell or triggering the cell’s self-destruction. Or, even worse, the microbe can figure out how to replicate inside this white blood cell and produce more copies of itself.
So how do you make sure that the process goes well, that the viral particle of SARS-COV-2 that is eaten up by your phagocytes doesn’t start causing trouble before you throw it into the combustion chamber? To start with, remember that your phagocytes aren’t going to eat something, unless it’s covered with antibodies that allow it to pass into the cell and stop the cell wall from repelling it. Then to make sure it goes right, you need to make sure that the dangerous zones of this virus are covered with neutralizing antibodies. If this goes wrong, the virus can enter the phagocyte and damage it.
People looked at the monocytes and found that they were productively infected by SARS-COV-2 with the aid of antibodies. They didn’t see evidence that the vaccine aided productive infection, but you have to keep in mind they looked at vaccinated recipient who had received their second dose of vaccine three weeks earlier and they were looking at versions of SARS-COV-2 that predate Omicron. The enhancing effect of antibodies is dose-dependent. The same antibody can be neutralizing or enhancing, depending on its concentration.
Others have found evidence that SARS-COV-2 can replicate in B-lymphocytes, T-lymphocytes and monocytes. Again, this would be expected to happen due to the virus being drawn into these cells by antibodies.
I have now covered the Fcr pathway, but there is another pathway that needs to be mentioned: The complement dependent pathway. SARS-COV-2 is also capable of infecting these cells through complement binding to the antibodies that cover the virus. Your phagocytes also have a complement receptor, where complement can bind. Complement can be thought of as a kind of additional building brick. When a bunch of antibodies bind to an antigen in a region close together to each other, complement then attaches to those antibodies to help strengthen their functions. Complement encourages phagocytosis to proceed.
When it comes to complement, it’s important to remember that it depends on antibodies being close together. If your antibodies are sporadically over wide sections of a particle, complement can’t bind to them. Take a look at the antibody repertoire against the Spike protein of vaccinated and naturally immune people:
You need to look at the top-left image. Darker spots are enriched for antibodies. Tell me, where do you see “dark stripes” and where do you see “random spots”? With the exception of the fusion protein region, I see dark stripes in vaccinated people and I see mostly random spots in naturally immune people. When I do see some dark stripes in naturally immune people, I see them in different parts of the genome, whereas I see them in the same places in vaccinated people.
So if you agree with me here, then what would you expect? You would expect more complement binding to take place in the immune response of vaccinated people. And a study looked at this, it confirmed our expectation. The ratio of complement to antibodies is much higher in vaccinated people than in the naturally immune:
And so what happens when you have complement that binds to poorly neutralizing antibodies that bound themselves to the Spike protein? This complement binds to the white blood cell’s complement receptor, the whole viral-antibody-complement complex is then drawn into the white blood cell, then something goes wrong, the virus escapes its journey to the furnace and begins to replicate in the white blood cell. This is a form of complement mediated antibody dependent enhancement, which has been seen with a number of viruses, including SARS-COV-2.
If we have people who are continually being reinfected, only to then deploy an immune response that enables SARS-COV-2 to damage and even productively infect their white blood cells, then you would expect immune system damage to become a possibility. Considering that the vaccinated are stuck with an immune response that fails to shift towards Omicron variants and thus becomes increasingly non-neutralizing, we would expect this problem to be more significant among the vaccinated share of the population, although some degree of immune damage was already being observed in patients before the vaccines were deployed.
So how would you prevent this mess from happening?
You would want to induce an immune response that is:
-Mostly IgM dominated. The Fc receptors don’t typically bind IgM, they mostly bind IgG1 and IgG3. The complement also depends on these IgG antibodies, whereas the body generally mainly uses IgM to neutralize SARS-COV-2 if left to its own crevices. There is a special kind of Fc receptor for IgM, only expressed on your NK cells, B cells and T cells.
-The IgG antibodies that you do deploy against this virus should be more strewn out across the Spike protein. We don’t want them to be clustering closely together and we definitely don’t want the whole population to have them cluster closely together in the same regions!
-You want a healthy ratio of neutralizing to binding antibodies. You would never hear me claim that binding antibodies are useless, but when the ratio is wrong, your poor phagocytes will be gobbling up this virus, only for the virus to break loose on its way to the furnace!
Natural immunity accomplishes such an immune response of course, but with a price: The risk of disease. In the long run however, I expect that most of the population paying that price would have been a far wiser decision, than to leave the whole population stuck with this IgG dominated, poorly neutralizing, high complement inducing, homogeneous immune response.
Antibody dependent enhancement can take different forms, you can look through the literature and see that we’re already observing it taking place with SARS-COV-2, especially with the Omicron variants. This doesn’t necessarily mean that the hospitals collapse overnight, or that people end up in the ICU suffering ARDS, or other highly visual nightmarish scenarios.
Rather, if the antibody dependent enhancement we observe means that your white blood cells are being damaged or killed because the virus is drawn into them, covered in chains that are not as strong as your white blood cells would expect them to be, then the outcome you would expect is immune system damage.
It would have been nice to have some form of vaccine against this virus, to administer to elderly at high risk of succumbing to it, but it should be obvious that these new high-tech vaccines that we did receive were never a proper solution for anyone. Now the whole Western population is stuck with a highly homogeneous immune response against this virus that facilitates damage to the immune system. The Chinese seem to realize the failure of these vaccines, hence why they’re still not letting the mRNA shots into their country.
Because they insisted on giving these failed vaccines to everyone, not just the elderly, we’re now stuck with this highly homogeneous immune response in our population for decades to come. And considering the failure of their whole experiment, if they ever do get it right, anyone smart enough to anticipate the failure of their original experiment would refuse to participate in the next experiment.
You don’t really notice it when your white blood cells are being damaged or killed. They’re mobile cells, they won’t send your brain a pain signal. People with HIV will have initial symptoms, but then as the depletion of their T-cells sets in, they don’t notice anything wrong until their CD4+ T cell count gets very low and they start suffering opportunistic infections.
Overall you would expect successive variants to get better at injuring, killing and/or replicating in white blood cells. The reason of course is because they will evade the most neutralizing antibodies, while continuing to recall the poorly neutralizing ones. These poorly neutralizing antibodies will continue to cover the viral particles (opsonization) so they can be absorbed by our phagocytes, but because they’re binding weakly and attract complement, they become increasingly capable of escaping on their way to the furnace.
How bad it gets depends among other factors on whether this damage to our white blood cells is a vital step in the overall transmission chain from person to person, or whether the particles that end up there are just “dead branches”, that causes us damage, but don’t significantly help the virus spread. My suspicion is that they help the virus in its replication cycle, but mainly somewhat indirectly: The viral particles that are damaging your white blood cells, allow their brothers and sisters to replicate themselves without getting caught by those same white blood cells. If I am correct then this would mean that the damage caused to our immune system is a trait that is under positive selection.