The study revealed that the SARS-CoV-2 virus can infect certain types of immune cells called monocytes and macrophages. Monocytes and macrophages are white blood cells and work in the front line of the immune system. Their job is to circulate in the blood and tissues, to find and destroy pathogens. They do this by eating – or really, surrounding and absorbing – threats such as viruses to prevent them from infecting other cells. Once a bad agent is absorbed, these cells have what can best be described as a cellular waste dump, called an endosome, that normally shuts off the infectious agent. In the case of the SARS-CoV-2 virus, however, this is not the case. The virus leaves the endosome and escapes to the cell body, where it begins to make copies of itself. “Not only are viruses absorbed, but once absorbed, the virus begins to reproduce, so that was amazing,” said Dr. Judith Lieberman, a pediatric immunologist at Boston Children’s Hospital, who led the study. A virus that starts making copies of itself in the body is never a good thing, but when it does happen to these protective cells, it triggers a series of next-level alarms.
Fiery death
These alarms, in turn, call for agents called inflammatory bodies that, in effect, respond by burning them all. They help the infected cell to die by fire, or “fiery death”. Rainfall is a recently recognized phenomenon. It also occurs in other diseases, such as sepsis. “When cells die from a fire, they release all kinds of inflammatory proteins that cause fever and call more immune cells to the spot,” Lieberman said. It launches a cascade of crisis signals that are very difficult to stop. “We have no way of dealing with it when it starts. It’s something like a small fire. It is spreading and exploding and no fire extinguisher is able to put it out,” he said. “I think it’s really stylish,” said Donna Farber, a professor of microbiology and immunology at Columbia University, describing the study. “They actually put in some pieces that had not been collected before.” He did not participate in the investigation. Comparing the blood cells of healthy people with those of people who went to the hospital with Covid-19 and with the blood of people who had pneumonia of other causes, the researchers found that this process appears to be more common with Covid-19. “All the patients we studied had signs of respiratory distress and pneumonia. [SARS-CoV-2] “He had a lot more of these inflammatory cells and dying cells,” Lieberman said. “It simply came to our notice then [SARS-CoV-2] he’s very good at provoking it, but we do not know why. “ Lieberman said the study also helps explain why people who are older or have underlying health problems such as obesity or diabetes have a higher risk of serious side effects with Covid-19. These conditions are already associated with some level of inflammation in the body. “These inflammatory fires are much, much more likely to start,” he said. “They have a kind of low slow burning that happens anyway. And once it starts it ‘s really hard to put out the fire.”
The role of antibodies
There is another part of the process, however, that suggests a way it could be stopped, and that is the way the virus enters these white blood cells. Monocytes and macrophages lack ACE-2 receptors, the gateway that the virus uses to bind and infect other cell types. Instead, the virus enters these cells because of another helper of the immune system – the Y-shaped antibodies that grab the virus in an attempt to prevent it from attaching to our cells. When the antibodies grab the viruses, the antibody tail – called the FC segment – protrudes. This stalk acts as a flag to wave monocytes and macrophages to inform them that there is a bad guy to pick up. Not all monocytes recognize the same antibodies. The study found that people with Covid-19 tended to have more of an unusual monocyte type that had CD16 receptors. These receptors recognize the antibody stems that the body generates to fight the SARS-CoV-2 virus. These antibodies bind to monocytes with CD16 receptors, activating the cell to absorb the virus. Once inside, the virus begins to try to replicate itself, triggering a devastating inflammatory response. John Wherry, director of the Institute of Immunology at Perelman University School of Medicine at the University of Pennsylvania, said: Wherry did not participate in the study. He said this could happen to other infections, such as dengue fever. The more times a person becomes infected with the dengue virus, the more they get sick with each subsequent period. This is the opposite of what is supposed to happen. A person recovering from an infection usually has better protection than future ones.
Drug targets
Wherry said there was no evidence that the antibodies that facilitate these severe inflammatory reactions came from previous infections or other types of coronaviruses. He said that antibodies are produced rapidly in infections and that those that work here were probably created in response to the individual’s current illness. In this way, it is different from what happens with dengue fever. However, the antibodies produced by the vaccines do not appear to facilitate the monocyte infections and cataracts of inflammation that follow. They tried it in the study. “I think what was interesting about this was that it could give an indication and maybe even some goals that can be addressed about why some of the inflammation we see in patients with severe Covid may start in the wrong way or come out. out of control, “Wherry said. “So I think that’s very interesting.”
