This month, a paper that had been awaiting publication for over a year finally saw public distribution. This paper showed two things:
COVID-19 causes cells in the body to undergo pyroptosis. Pyroptosis is a process of programmed cell death. Like its counterparts, apoptosis and ferroptosis, once the death-signaling process reaches a certain arc it cannot be stopped. Pyroptosis is a word formed from the Greek and Latin, pyro- meaning fire and -ptosis, meaning to fall.
What is happening in the body when this occurs? Well, scientists have not seen pyroptosis as a result of COVID in vivo (that is, in a living body), but they have seen it in other instances. Here are two short videos, the first showing what pyroptosis looks like in cell culture, the second describing the mechanics of how the process works. The first is about a minute; the second, about four.
What happens in COVID is that at some point, after the virus has entered the body, it becomes coated with an antibody, as the innate immune system attempts to perform its function. Then a monocyte—one of the body’s sentinel cells—encounters the antibodied virus, and the virus is able to be taken up into the monocyte via a certain molecule on its membrane (CD16).
That is the second thing the paper showed. COVID can be taken up by the body without ACE2 being present or involved.
Once the virus has been taken into the monocyte, the cell recognizes the danger. It releases DAMPs (damage-associated molecular patterns), which signal certain other proteins to assemble in order to create cytokines. This assembly is called an inflammasome. Once this assembly is completed, it causes a cascade that includes cleavage of a certain enzyme, caspase-1, which under a regular cascade could lead to apoptosis (a quiet cell death). But because the inflammasome has been assembled, the cell is programmed to explode.
From the paper:
When inflammasomes sense infection, they recruit the ASC adaptor and assemble into large complexes that recruit and activate caspase-1, which in turn processes interleukin(IL)-1 pro-cytokines and the pore-forming GSDMD to disrupt the cell membrane, leading to cell death and cytokine release.
In this case, because the cell knows that it has within it a deadly intruder (the virus is attempting to replicate inside the monocyte), it readies the cytokines to be released immediately and in a way that alerts surrounding cells. It cleaves Gasdermin-D (GSDMD), particles of which assemble to form a pore in the cell membrane. Once opened, the cell pours out the cytokines. The pore also allows water to rush into the cell in osmotic transfer, and this causes the cell to bloat and finally to burst spectacularly. This is pyroptosis.
This is the equivalent of setting oneself on fire. This is self-immolation, for the greater good.
The remnant of this ASC adaptor, called a speck, is one of the key ways the scientists were able to discover exactly what was occurring inside these cells. The inflammasome, once assembled, can easily be detected by microscopy; it is quite a large structure. The downstream products of some of these proteins can also be found, like evidence in a crime scene.
Crucially, this cycle does not seem to happen in combination with the vaccine. According to Boston’s Children’s Hospital,
More reassuringly, the team found that antibodies healthy people made in response to mRNA COVID-19 vaccines did not facilitate infection of monocytes in the lab. [Judy] Lieberman[, who lead the study] thinks that antibodies generated by the vaccine don’t attach as well to CD16 receptors. As a result, when vaccinated people are exposed to COVID-19, their monocytes may not take the virus up, so they are protected.
So, under normal circumstances, “[a]bout 10% of monocytes and 8% of lung macrophages in COVID-19 patients were SARS-CoV-2-infected,” but that was not true when vaccination entered the picture. Monoclonal antibodies also suppressed this effect, but the authors of the study caution that they must be provided promptly to measurably intervene.
A few things important to note:
- Two inflammasomes were initiated, one by NLRP3 and the other by AIM2. The former recognizes signals from DAMPs, the latter is triggered by double-stranded DNA. The researchers believe AIM2 may be activated as mitochondria in the host (that is, the human body) leave the cell or otherwise sustain damage.
- “Although inflammasome activation was detected in virtually every infected monocyte/macrophage, it was not detected in lung epithelial cells,” the scientists say. They are unsure why the lung epithelial cells were spared. They encourage further study.
“We found a one-to-one correspondence between monocyte infection and inflammasome-caspase-1 activation and pyroptosis,” the scientists state. “Most dying monocytes in COVID-19 blood had activated inflammasomes, suggesting that monocytes are dying of pyroptosis. This is a large number, considering that dying cells are rapidly eliminated in vivo.”
The scientists also address why this finding had not been noted before.
It may be surprising that monocyte infection and cell death has not been widely recognized. However, this may be because (1) many COVID-19 studies use thawed, frozen cells, and dying cells do not survive freeze-thawing, (2) published studies have not looked at whether circulating mononuclear cells are dying, and (3) few researchers have looked for monocyte infection because monocytes do not express ACE2.
Simply put, most folks did not know why to look. There was ample reason to focus on ACE2 as a culprit and little reason to suspect monocytes as having an active role in the infection process. However, due to this cycle of pyroptosis, the body is releasing large loads of cytokines, possibly triggering cytokine storm through this process, creating a cascade of more inflammasome assembly. “Four times as many lung-resident macrophages had activated inflammasomes as were infected,” the team states, which can cause a vicious cycle of inflammation.
This study focused only on what is going in the blood of COVID-19 patients. I personally am concerned about what is going on in the brains of these patients. We have reason to believe that the blood-brain barrier is disrupted or disturbed in COVID, which may make it easier for these monocytes to find their way into the brain parenchyma, where the neurons and supporting cells reside. Microglia are the brain’s equivalent of monocytes/macrophages. We already know that microglia are implicated in profound neuroinflammation in COVID patients; we just don't have (as far as I know) definitive proof that pyroptosis is occurring there. I have my suspicions.
So when Senator Ron Johnson goes out and claims without any shame that the COVID vaccine may cause AIDS (so offensive to me, as I have a family member with HIV, and the immunocompromised are exactly the people who are most susceptible to folks who refuse to get vaccinated), someone might want to ask him whether he’d rather have the cells in his body begin to go off like pre-programmed hand grenades. These are your choices, Senator.